WorldWideScience

Sample records for spokane nl 11-2

  1. NL Kids online

    OpenAIRE

    Jos de Haan

    2010-01-01

    In Nederland, maar ook elders, verkennen jongeren intensief de mogelijkheden van internet. Deze verkenning begint overal op steeds jongere leeftijd. Jongeren krijgen te maken met zowel de positieve als de negatieve kanten van internet. Dit rapport bestudeert de aangeboden kansen en risico's van online activiteiten en komt met aanbevelingen hoe we positief gebruik kunnen stimuleren en de risico's beperken. NL Kids online is gebaseerd op de belangrijkste rapporten van het EU Kids online project...

  2. Spokane Tribal Hatchery, 2002 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Peone, Tim L. (Spokane Tribe of Indians, Willpinit, WA)

    2003-03-01

    The Spokane Tribal Hatchery (Galbraith Springs) project originated from the Northwest Power Planning Council (NPPC) 1987 Columbia Basin Fish and Wildlife Program. The goal of this project is to aid in the restoration and enhancement of the Lake Roosevelt and Banks Lake fisheries adversely affected by the construction and operation of Grand Coulee Dam. The objective is to produce kokanee salmon and rainbow trout for release into Lake Roosevelt for maintaining a viable fishery. The goal and objective of this project adheres to the NPPC Resident Fish Substitution Policy and specifically to the biological objectives addressed in the NPPC Columbia River Basin Fish and Wildlife Program to mitigate for hydropower related fish losses in the blocked area above Chief Joseph/Grand Coulee Dams.

  3. Spokane Tribal Hatchery, 2003 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Peone, Tim L. (Spokane Tribe of Indians, Wellpinit, WA)

    2004-05-01

    Due to the construction and operation of Grand Coulee Dam (1939), anadromous salmon have been eradicated and resident fish populations permanently altered in the upper Columbia River region. Federal and private hydropower dam operations throughout the Columbia River system severely limits indigenous fish populations in the upper Columbia. Artificial production has been determined appropriate for supporting a harvestable fishery for kokanee salmon (Oncorhynchus nerka) and rainbow trout (Oncorhynchus mykiss) in Lake Roosevelt and Banks Lake (Grand Coulee Dam impoundments). A collaborative multi-agency artificial production program for the Lake Roosevelt and Banks Lake fisheries exists consisting of the Spokane Tribal Hatchery, Sherman Creek Hatchery, Ford Trout Hatchery and the Lake Roosevelt Kokanee and Rainbow Trout Net Pen Rearing Projects. These projects operate complementary of one another to target an annual release of 1 million yearling kokanee and 500,000 yearling rainbow trout for Lake Roosevelt and 1.4 million kokanee fry/fingerlings for Banks Lake. Combined fish stocking by the hatcheries and net pen rearing projects in 2003 included: 899,168 kokanee yearlings released into Lake Roosevelt; 1,087,331 kokanee fry/fingerlings released into Banks Lake, 44,000 rainbow trout fingerlings and; 580,880 rainbow trout yearlings released into Lake Roosevelt. Stock composition of 2003 releases consisted of Lake Whatcom kokanee, 50:50 diploid-triploid Spokane Trout Hatchery (McCloud River) rainbow trout and Phalon Lake red-band rainbow trout. All kokanee were marked with either thermal, oxytetracyline or fin clips prior to release. Preliminary 2003 Lake Roosevelt fisheries investigations indicate hatchery/net pen stocking significantly contributed to harvestable rainbow trout and kokanee salmon fisheries. An increase in kokanee harvest was primarily owing to new release strategies. Walleye predation, early maturity and entrainment through Grand Coulee Dam continues to

  4. Spokane Tribal Hatchery, 2005 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Peone, Tim L. (Spokane Tribe of Indians, Wellpinit, WA)

    2006-03-01

    Due to the construction and operation of Grand Coulee Dam (1939), anadromous salmon have been eradicated and resident fish populations permanently altered in the upper Columbia River region. Federal and private hydropower dam operations throughout the Columbia River system severely limits indigenous fish populations in the upper Columbia. Artificial production has been determined appropriate for supporting harvestable fisheries for kokanee salmon (Oncorhynchus nerka) and rainbow trout (Oncorhynchus mykiss) in Lake Roosevelt and Banks Lake (Grand Coulee Dam impoundments). The Spokane Tribe, Washington Department of Fish and Wildlife, Colville Confederated Tribes and Lake Roosevelt Development Association/Lake Roosevelt Volunteer Net Pen Project are cooperating in a comprehensive artificial production program to produce kokanee salmon (Oncorhynchus nerka) and rainbow trout (Oncorhynchus mykiss) for annual releases into the project area. The program consists of the Spokane Tribal Hatchery, Sherman Creek Hatchery, Ford Trout Hatchery and Lake Roosevelt Rainbow Trout Net Pen Rearing Projects. The Lake Roosevelt and Banks Lake Fisheries Evaluation Program monitor and evaluates release strategies and production methods for the aforementioned projects. Between 1985 and 2005 the projects have collectively produced up to 800,000 rainbow trout and 4 million kokanee salmon for release into Lake Roosevelt and 1.4 million kokanee fry for Banks Lake annually. In 2005, the annual release goal included 3.3 million kokanee fry, 475,000 kokanee yearlings and 500,000 rainbow trout yearlings. Fish produced by this project in 2005 to meet collective fish production and release goals included: 3,446,438 kokanee fingerlings, 347,730 rainbow trout fingerlings and 525,721 kokanee yearlings. Kokanee yearlings were adipose fin clipped before release. Stock composition consisted of Meadow Creek and Lake Whatcom kokanee, diploid-triploid Spokane Trout Hatchery (McCloud River) rainbow trout and

  5. Spokane Tribal Hatchery, 2004 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Peone, Tim L. (Spokane Tribe of Indians, Wellpinit, WA)

    2005-03-01

    Due to the construction and operation of Grand Coulee Dam (1939), anadromous salmon have been eradicated and resident fish populations permanently altered in the upper Columbia River region. Federal and private hydropower dam operations throughout the Columbia River system severely limits indigenous fish populations in the upper Columbia. Artificial production has been determined appropriate for supporting a harvestable fishery for kokanee salmon (Oncorhynchus nerka) and rainbow trout (Oncorhynchus mykiss) in Lake Roosevelt and Banks Lake (Grand Coulee Dam impoundments). A collaborative multi-agency artificial production program for the Lake Roosevelt and Banks Lake fisheries exists consisting of the Spokane Tribal Hatchery, Sherman Creek Hatchery, Ford Trout Hatchery and the Lake Roosevelt Kokanee and Rainbow Trout Net Pen Rearing Projects. These projects operate complementary of one another to target an annual release of 1 million yearling kokanee and 500,000 yearling rainbow trout for Lake Roosevelt and 1.4 million kokanee fry/fingerlings for Banks Lake. Fish produced by this project in 2004 to meet collective fish production and release goals included: 1,655,722 kokanee fingerlings, 537,783 rainbow trout fingerlings and 507,660 kokanee yearlings. Kokanee yearlings were adipose fin clipped before release. Stock composition consisted of Lake Whatcom kokanee, 50:50 diploid-triploid Spokane Trout Hatchery (McCloud River) rainbow trout and Phalon Lake red-band rainbow trout. All kokanee were marked with either thermal, oxytetracyline or fin clips prior to release. Preliminary 2004 Lake Roosevelt fisheries investigations indicate hatchery/net pen stocking significantly contributed to harvestable rainbow trout and kokanee salmon fisheries. An increase in kokanee harvest was primarily owing to new release strategies. Walleye predation, early maturity and entrainment through Grand Coulee Dam continues to have a negative impact on adult kokanee returns and limits the

  6. The NAL-NL2 prescription procedure

    Directory of Open Access Journals (Sweden)

    G. Keidser

    2011-03-01

    Full Text Available NAL-NL2 is the second generation of prescription procedures from The National Acoustic Laboratories (NAL for fitting wide dynamic range compression (WDRC instruments. Like its predecessor NALNL1 (Dillon, 1999, NAL-NL2 aims at making speech intelligible and overall loudness comfortable. This aim is mainly driven by a belief that these factors are most important for hearing aid users, but is also driven by the fact that less information is available about how to adjust gain to optimise other parameters that affect prescription such as localisation, tonal quality, detection of environmental sounds, and naturalness. In both formulas, the objective is achieved by combining a speech intelligibility model and a loudness model in an adaptive computer- controlled optimisation process. Adjustments have further been made to the theoretical component of NAL-NL2 that are directed by empirical data collected during the past decade with NAL-NL1. In this paper, the data underlying NAL-NL2 and the derivation procedure are presented, and the main differences from NAL-NL1 are outlined.

  7. Behoeftepeiling onder de doelgroep van themapagina's Gezond Werk : Loketgezondleven.nl en Nisb.nl

    NARCIS (Netherlands)

    Wesselman M; van Dijk SA; CGL; vz

    2012-01-01

    Er is onderzoek uitgevoerd naar de informatiebehoefte van de doelgroep van twee websites rond Gezond Werk: Loketgezondleven.nl/settings/werk en Nisb.nl/werk. Het RIVM Centrum Gezond Leven (CGL) en het Nederlands Instituut voor Sport en Bewegen (NISB) voerden gezamenlijk dit onderzoek uit. Hiermee

  8. Ontwerprapport 2005 kiesBeter.nl

    NARCIS (Netherlands)

    Loon AJM van; PCAl Droomers; E Keesman; H Janssen; JAM Lijdsman; HB Mulder; Veen AA van der; Vrijsen WJJ; VTV

    2005-01-01

    Since September 2004 RIVM's Centre for Public Health Forecasting (VTV) in the Netherlands has been working on the development of an Internet portal for the general public called kiesBeter.nl ('Make a better choice'). Via this portal, consumers will have access to integrated information on health,

  9. Ground-Water Flow Model for the Spokane Valley-Rathdrum Prairie Aquifer, Spokane County, Washington, and Bonner and Kootenai Counties, Idaho

    Science.gov (United States)

    Hsieh, Paul A.; Barber, Michael E.; Contor, Bryce A.; Hossain, Md. Akram; Johnson, Gary S.; Jones, Joseph L.; Wylie, Allan H.

    2007-01-01

    This report presents a computer model of ground-water flow in the Spokane Valley-Rathdrum Prairie (SVRP) aquifer in Spokane County, Washington, and Bonner and Kootenai Counties, Idaho. The aquifer is the sole source of drinking water for more than 500,000 residents in the area. In response to the concerns about the impacts of increased ground-water withdrawals resulting from recent and projected urban growth, a comprehensive study was initiated by the Idaho Department of Water Resources, the Washington Department of Ecology, and the U.S. Geological Survey to improve the understanding of ground-water flow in the aquifer and of the interaction between ground water and surface water. The ground-water flow model presented in this report is one component of this comprehensive study. The primary purpose of the model is to serve as a tool for analyzing aquifer inflows and outflows, simulating the effects of future changes in ground-water withdrawals from the aquifer, and evaluating aquifer management strategies. The scale of the model and the level of detail are intended for analysis of aquifer-wide water-supply issues. The SVRP aquifer model was developed by the Modeling Team formed within the comprehensive study. The Modeling Team consisted of staff and personnel working under contract with the Idaho Department of Water Resources, personnel working under contract with the Washington Department of Ecology, and staff of the U.S. Geological Survey. To arrive at a final model that has the endorsement of all team members, decisions on modeling approach, methodology, assumptions, and interpretations were reached by consensus. The ground-water flow model MODFLOW-2000 was used to simulate ground-water flow in the SVPR aquifer. The finite-difference model grid consists of 172 rows, 256 columns, and 3 layers. Ground-water flow was simulated from September 1990 through September 2005 using 181 stress periods of 1 month each. The areal extent of the model encompasses an area of

  10. 19 CFR 11.2 - Manufactured tobacco.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Manufactured tobacco. 11.2 Section 11.2 Customs... PACKING AND STAMPING; MARKING Packing and Stamping § 11.2 Manufactured tobacco. (a) If the invoice and entry presented for manufactured tobacco specify all the information necessary for prompt determination...

  11. 76 FR 27668 - ASC Machine Tools, Inc., Spokane Valley, WA; Notice of Negative Determination on Reconsideration

    Science.gov (United States)

    2011-05-12

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-72,971] ASC Machine Tools, Inc... workers and former workers of ASC Machine Tools, Inc., Spokane Valley, Washington (the subject firm). The..., component parts of equipment, and spare parts. Workers are not separately identifiable by article produced...

  12. Sistemik Hipertansiyonlu Olgularda Santral Kornea Kalınl??? ve Retina Sinir Lifi Tabakası Kalınl???

    OpenAIRE

    ERG?N, Ahmet; ÇAKMAK, Yasin; GÜLLÜ, Reyhan

    2007-01-01

    Bu çalışma, sistemik hipertansiyonlu hastalarda santral kornea kalınl??? ve retina sinir lifi tabakası kalınl???nı ara?tırmak için planland?. Olguların santral kornea kalınlıkları (SKK) Pacline Optikon Ultrasonik pakimetre cihazı ile ölçüldü. Retina sinir lifi tabakası kalınl??? (RSLTK) ölçümü ise NFA II, GDx VCC cihazı ile yapıld?. Her olgu için üç ölçüm yapıld?, bunlardan en net olanı hesapland?. Sağlıklı bireyler ile sistemik hipertansiyonu olan hastalar arasında tüm ölçümler açıs?ndan ist...

  13. [What do you think of Thuisarts.nl? Experiences after 3 years of www.Thuisarts.nl].

    Science.gov (United States)

    Drenthen, Ton; Beijaert, Roy P H; Jansen, Patrick W M; Korevaar, Joke C; Smeele, Ivo J M

    2014-01-01

    Many people need information on health and disease, but the internet is a maze of medical information. In order to offer patients reliable medical information, and to support general practitioners, the Dutch College of General Practitioners (NHG) set up the public website Thuisarts.nl in 2011, which was later followed by an app. The NHG members survey amongst general practitioners from June 2013 showed that 90% of the general practitioners used Thuisarts.nl. The number of visitors was on average 60,000 a day. Information is also available from questionnaires filled in by the NIVEL Health Care Consumer Panel (n = 2846) and participants in a study on information technology and independence (n = 25). Thuisarts.nl meets an important need and is highly valued by doctors and patients. There are plans for the further development of Thuisarts.nl including short videos, illustrations, searchable anatomical structures and information from other reliable organisations such as associations of specialist doctors.

  14. Notification: EPA Region 10 Management Controls Over Allowing Substantial Public Funds to Construct the Spokane County Wastewater Treatment Facility

    Science.gov (United States)

    January 20, 2012. This EPA's OIG is initiating a review from an OIG hotline complaint regarding whether federal funds were properly used to construct the new Spokane County wastewater treatment facility in accordance with 40 CFR 35, Subpart K.

  15. Long-term Planning for Sustainable Water and Wastewater Infrastructure in Wellpinit, Washington, for the Spokane Tribe of Indians

    Science.gov (United States)

    The Spokane Tribe initiated a long-term planning process for a water and wastewater infrastructure system that can support the tribe’s goals to add compact, mixed-use development in the town of Wellpinit.

  16. 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A S; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

    2015-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of

  17. 32 CFR 11.2 - Authority.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Authority. 11.2 Section 11.2 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS CRIMES AND ELEMENTS FOR TRIALS... in the War Against Terrorism,” (66 FR 57833) and 10 U.S.C. 113(d), 140(b), and 821. The provisions of...

  18. Ecological indicators of water quality in the Spokane River, Idaho and Washington, 1998 and 1999

    Science.gov (United States)

    MacCoy, Dorene E.; Maret, Terry R.

    2003-01-01

    A water-quality investigation of the Spokane River was completed during summer low-flow conditions in 1998 and 1999 as part of the USGS NAWQA Program, in cooperation with the WDOE. (Abbreviations used in this report are defined on the last page.) Samples for analyses of water chemistry; bed sediment; aquatic communities (fish, macroinvertebrates, and algae); contaminants in tissue (fish and macroinvertebrates); and associated measures of habitat were collected at six sites downstream from Coeur d’Alene Lake between river miles 63 and 100. These data provided baseline information to evaluate the water-quality status of the Spokane River and can be used to determine the ecological risk to aquatic organisms from contaminants.

  19. Metropolitan Spokane Region Water Resources Study. Appendix E. Environment and Recreation

    Science.gov (United States)

    1976-01-01

    Q ATER:a-ESOURCE8 STUDY pet ropoli an no APPENDIX E En- go n a o -Ir LIST OF REPORTS AND APPENDICES REPORTS Summary Report Technical Report APPEND...AnimalsSmall Animals 315.52- 1Muskrats 315.52- 2Mink 315.52- 2 Beaver 315.52- 3Racoon 315.52- 3 Otter 315.52- 3Bobcat 315.52- 3Aquatic Game Birds 315.52...racoon, otter and bobcats ar- present in varying numbers in the etudy area. Fur-bearing animals are generally abundant throughout the en- tire Spokane

  20. 22q11.2 deletion syndrome

    Science.gov (United States)

    McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

    2016-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754

  1. Clinical manifestations of human coronavirus NL63 infection in children in Taiwan

    NARCIS (Netherlands)

    Wu, Ping-Sheng; Chang, Luan-Yin; Berkhout, B.; van der Hoek, L.; Lu, Chun-Yi; Kao, Chuan-Liang; Lee, Ping-Ing; Shao, Pei-Lan; Lee, Chin-Yun; Huang, Fu-Yuan; Huang, Li-Min

    2008-01-01

    Human coronavirus NL63 (HCoV-NL63) is a global respiratory tract pathogen; however, the epidemiology of this virus in subtropical area is not well known. To evaluate the epidemics and disease spectrum of HCoV-NL63 infection in children in Taiwan, we prospectively screened children admitted to the

  2. Named Entity Recognition in a Hungarian NL Based QA System

    Science.gov (United States)

    Tikkl, Domonkos; Szidarovszky, P. Ferenc; Kardkovacs, Zsolt T.; Magyar, Gábor

    In WoW project our purpose is to create a complex search interface with the following features: search in the deep web content of contracted partners' databases, processing Hungarian natural language (NL) questions and transforming them to SQL queries for database access, image search supported by a visual thesaurus that describes in a structural form the visual content of images (also in Hungarian). This paper primarily focuses on a particular problem of question processing task: the entity recognition. Before going into details we give a short overview of the project's aims.

  3. Hobo Orator Union: Class Composition and the Spokane Free Speech Fight of the Industrial Workers of the World

    Science.gov (United States)

    May, Matthew S.

    2011-01-01

    From 1909 to 1910, the public performance of soap-box oratory began to effect dramatic changes in the composition of migrant workers throughout the Pacific Northwest. Municipal authorities in Spokane attempted to curb the formation of a union of hobo orators by outlawing public speech-making within the city fire limits. The ensuing confrontation…

  4. 77 FR 12873 - Draft Environmental Impact Statement for the Proposed Spokane Tribe of Indians West Plains Casino...

    Science.gov (United States)

    2012-03-02

    ... structure, site retail, commercial building, tribal cultural center, and police/ fire station within the... Main Street, Spokane, Washington 99201. The DEIS is also available online at: http://www.westplainseis... shown in the ADDRESSES section of this notice, during regular business hours, 8 a.m. to 4:30 p.m...

  5. [22q11.2 microdeletion].

    Science.gov (United States)

    Schneider, M; Eliez, S

    2010-04-01

    22q11.2 deletion syndrome (22q11DS), most frequently caused by a de novo microdeletion on the long arm of chromosome 22, is one of the most common neurogenetic syndromes. The cognitive and behavioral characteristics associated with the 22q11.2 phenotype can be quite heterogeneous, part of the reason the syndrome is often detected very late, if at all. Though in individuals with more severe cardiac, respiratory, or speech and language problems, 22q11DS is more easily detected at a young age. The cognitive profile in 22q11DS varies between borderline IQ and mild mental retardation. Less than half children have mental retardation but a majority suffer from learning difficulties. It is also typically characterized by a verbal-visual dissociation, with verbal abilities higher than visuo-spatial and abstract reasoning. Psychiatric comorbidity is also frequent in 22q11DS, and the presence of psychotic symptoms in pre-adolescence may be unique to the syndrome. In older adolescents and young adults, social withdrawal often becomes more intense and can be an indicator of psychiatric disorder. Neuroimaging studies in 22q11DS indicate different patterns of structural alterations in affected children and adults that directly relate to cognitive impairments in the syndrome. For these reasons, we believe that treatment of persons affected by 22q11DS should include periodic evaluations and frequent clinical check-ups that integrate recommendations for medical, speech, psychiatric, and academic problems. Copyright 2009 Elsevier Masson SAS. All rights reserved.

  6. Potential Hydroelectric Power Upriver Dam: City of Spokane Department of Utilities Water Division

    Energy Technology Data Exchange (ETDEWEB)

    1979-02-01

    The technical, economic, environmental and institutional feasibility of increasing the power generation capacity of the City of Spokane's Upriver Dam Complex by installing additional generating facilities and/or modifying existing facilities were studied. It is proposed that the existing powerhouse be uprated from 3.9 to 4.5 MW and that a new powerhouse be constructed with two 4.5 MW turbines to provide an annual additional energy production of 62.3 million kWh. No adverse environmental or safety effects are foreseen, the socio-institutional impacts will be beneficial, there is a market for the power produced, and the benefit/cost ratio is advantageous. (LCL)

  7. Electric dipole f values for Fe II J=9/2->11/2^o transitions

    Science.gov (United States)

    Beck, Donald R.

    2007-06-01

    Relativistic configuration-interaction f values have been obtained for all transitions between the lowest 17 J=9/2 and the lowest 27 J=11/2^o levels. The 35 f values >0.01 have an average gauge agreement of 3.6% and generally agree well with the semi-empirical results of Raassen ootnotetextA. J. J. Raassen, ftp://ftp.wins.uva.nl/pub/orth/iron/FeII.E1 (1999).. The near degeneracy of many of the odd levels requires the introduction of small semi-empirical energy shifts ootnotetextD. R. Beck, Phys. Scr. 71, 447 (2005).. A systematic way of estimating radial convergence is discussed.

  8. Genetics Home Reference: 22q11.2 deletion syndrome

    Science.gov (United States)

    ... Health Conditions 22q11.2 deletion syndrome 22q11.2 deletion syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description 22q11.2 deletion syndrome (which is also known by several other ...

  9. Genetics Home Reference: 22q11.2 duplication

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions 22q11.2 duplication 22q11.2 duplication Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description 22q11.2 duplication is a condition caused by an extra ...

  10. The BSID-II-NL for assessing children with specific impairments

    NARCIS (Netherlands)

    Ruiter, Selma Anne José

    2007-01-01

    Abstract In this doctoral thesis the Dutch standardization and validation of the Bayley Scales of Infant Development – Second Edition (BSID-II-NL) and its adapted versions for use with children with specific impairmens are presented. The BSID-II-NL is a standardized and norm-referenced instrument to

  11. Reduced Fertility in Male Mice Deficient in the Zinc Metallopeptidase NL1

    Science.gov (United States)

    Carpentier, Mélanie; Guillemette, Christine; Bailey, Janice L.; Boileau, Guy; Jeannotte, Lucie; DesGroseillers, Luc; Charron, Jean

    2004-01-01

    Members of the M13 family of zinc metalloendopeptidases have been shown to play critical roles in the metabolism of various neuropeptides and peptide hormones, and they have been identified as important therapeutic targets. Recently, a mouse NL1 protein, a novel member of the family, was identified and shown to be expressed mainly in the testis as a secreted protein. To define its physiological role(s), we used a gene targeting strategy to disrupt the endogenous murine Nl1 gene by homologous recombination and generate Nl1 mutant mice. The Nl1−/− mice were viable and developed normally, suggesting that zygotic expression of Nl1 is not required for development. However, Nl1−/− males produced smaller litters than their wild-type siblings, indicating specific male fertility problems. Reduced fertility may be explained by two impaired processes, decreased egg fertilization and perturbed early development of fertilized eggs. These two phenotypes did not result from gross anatomical modifications of the testis or from impaired spermatogenesis. Basic sperm parameters were also normal. Thus, our findings suggest that one of the roles of NL1 in mice is related to sperm function and that NL1 modulates the processes of fertilization and early embryonic development in vivo. PMID:15121861

  12. Tekenradar.nl, een webplatform over tekenbeten en de ziekte van Lyme

    NARCIS (Netherlands)

    Harms, M.G.; Fonville, M.; Vliet, van A.J.H.; Bennema, S.; Hofhuis, A.; Beaujean, D.; Sprong, H.; Pelt, van W.; Wijngaard, van den C.C.

    2014-01-01

    Tekenradar.nl is een webplatform voor onderzoek naar teken en tekenoverdraagbare aandoeningen zoals de ziekte van Lyme. Het RIVM en Wageningen University hebben de website in 2012 gezamenlijk opgericht. Tekenradar.nl geeft informatie over tekenbeten en de ziekte van Lyme en een actuele voorspelling

  13. Radon and remedial action in Spokane River Valley residences: an interim report

    International Nuclear Information System (INIS)

    Turk, B.H.; Prill, R.J.; Fisk, W.J.; Grimsrud, D.T.; Moed, B.A.; Sextro, R.G.

    1986-03-01

    Fifty-six percent of 46 residences monitored in the Spokane River Valley in eastern Washington/northern Idaho have indoor radon concentrations above the National Council for Radiation Protection (NCRP) guidelines of 8 pCi/1. Indoor levels were over 20 pCi/1 in eight homes, and ranged up to 132 pCi/1 in one house. Radon concentrations declined by factors of 4 to 38 during summer months. Measurements of soil emanation rates, domestic water supply concentrations, and building material flux rates indicate that diffusion of radon does not significantly contribute to the high concentrations observed. Rather, radon entry is dominated by pressure-driven bulk soil gas transport, aggravated by the local subsurface soil composition and structure. A variety of radon control strategies are being evaluated in 14 of these homes. Sub-surface ventilation by depressurization and overpressurization, basement overpressurization, and crawlspace ventilation are capable of successfully reducing radon levels below 5 pCi/1 in these homes. House ventilation is appropriate in buildings with low-moderate concentrations, while sealing of cracks has been relatively ineffective

  14. Small-scale geodiversity and dirt road management, Ede (NL)

    Science.gov (United States)

    van den Ancker, Hanneke; Jungerius, Pieter Dirk

    2016-04-01

    A large part of the countryside roads on the Pleistocene sands of The Netherlands are dirt roads. Most are footpaths, but a small percentage are relatively heavily used by motorized vehicles. These latter roads are a cause subject of debate. Puddles and potholes develop during periods of wet weather, while dust whirls from the roads form during spells of dry weather as do washboard ripples. They cause problems for people living along these roads and tourists (walkers and bikers. The community of Ede (NL), like many other communities on the sand, wants to keep its 80 km of dirt roads because of the natural values they harbour as well as for their characteristic landscape quality and cultural heritage value. A part of the dirt roads in Ede is heavily used. In 2009, the community of Ede developed a decision model to support management of the dirt roads. Ede acknowledges that each dirt road is unique and asks for a tailor-made solution. Road maintenance measures include grading, making a camber, digging pits, applying loam or sandy loam. If problems become too large, one-way traffic can be an option. In more and more cases the dirt roads are barred for motorized through traffic (Gemeente Ede, 2009). As a reconnaissance we have studied the dirt roads of the Horabos/Horalaan over the last year. Incidentally we looked at other parts of the main Horalaan and the footpaths in the adjacent forest of Hoekelum. All dirt roads lie near the top of a Saalian push-moraine in which the upper course of dry valleys are present. Some results of the reconnaissance: - Most dirt roads sections in the Horabos lie lower than the surrounding terrain; - The problems develop in a short period of time during special weather conditions; - Certain dirt road sections e.g. those sections crossing a slight depression are quickly developing potholes; - Even a small slope of the road (car traffic improves the infiltration in the road, and reduces the run-off to other the road sections to nearly zero

  15. Epidemiology of human coronavirus NL63 infection among hospitalized patients with pneumonia in Taiwan

    Directory of Open Access Journals (Sweden)

    Su-Hua Huang

    2017-12-01

    Full Text Available Background/Purpose: Human coronavirus (HCoV NL63 is recognized in association with upper or lower respiratory tract illnesses in children. This study surveyed the prevalence of HCoV-NL63 and influenza viruses in patients with influenza-like illness in Taiwan during 2010–2011. Methods: Throat samples from 107 hospitalized patients with pneumonia and 175 outpatients with influenza-like illness were examined using real-time polymerase chain reaction assays with virus-specific primers, and then virus-positive specimens were confirmed by sequencing the polymerase chain reaction products. Results: HCoV-NL63 infection was identified in 8.4% (9/107 of hospitalized patients with pneumonia, but not found in outpatients with influenza-like illness. Age distribution of HCoV-NL63 infection in hospitalized patients with pneumonia indicated that the group aged 16–25 years (20% had the highest positive rate compared with the other groups, and exhibited a similar age-specific pattern to influenza A/H1N1 infection, but not influenza A/H3N2 and B infections in hospitalized patients. Seasonal prevalence of HCoV-NL63 infection was late winter, overlapping the highest peak of the influenza A/H1N1 epidemic during December 2010 to March 2011 in Taiwan. Co-infection of HCoV-NL63 and influenza A/H1N1 was detected in three hospitalized patients. Clinical manifestation analysis indicated that the main symptoms for HCoV-NL63 infection included fever (88.9%, cough (77.8%, and pneumonia (100%. Co-infection caused significantly higher rates of breathing difficulties, cough, and sore throat than those of single infection with HCoV-NL63 and influenza A/H1N1. Phylogenetic analysis indicated a low level of heterogeneity between Taiwan and global HCoV-NL63 strains. Conclusion: Understanding epidemiology of HCoV-NL63 in Taiwan provides an insight for worldwide surveillance of HCoV-NL63 infection. Keywords: age distribution, human coronavirus NL63, phylogenetic analysis

  16. 22q11.2 deletion syndrome in diverse populations.

    Science.gov (United States)

    Kruszka, Paul; Addissie, Yonit A; McGinn, Daniel E; Porras, Antonio R; Biggs, Elijah; Share, Matthew; Crowley, T Blaine; Chung, Brian H Y; Mok, Gary T K; Mak, Christopher C Y; Muthukumarasamy, Premala; Thong, Meow-Keong; Sirisena, Nirmala D; Dissanayake, Vajira H W; Paththinige, C Sampath; Prabodha, L B Lahiru; Mishra, Rupesh; Shotelersuk, Vorasuk; Ekure, Ekanem Nsikak; Sokunbi, Ogochukwu Jidechukwu; Kalu, Nnenna; Ferreira, Carlos R; Duncan, Jordann-Mishael; Patil, Siddaramappa Jagdish; Jones, Kelly L; Kaplan, Julie D; Abdul-Rahman, Omar A; Uwineza, Annette; Mutesa, Leon; Moresco, Angélica; Obregon, María Gabriela; Richieri-Costa, Antonio; Gil-da-Silva-Lopes, Vera L; Adeyemo, Adebowale A; Summar, Marshall; Zackai, Elaine H; McDonald-McGinn, Donna M; Linguraru, Marius George; Muenke, Maximilian

    2017-04-01

    22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P 22q11.2 DS with 156 age and gender matched controls and found that sensitivity and specificity were greater than 96% for all populations. In summary, we present the varied findings from global populations with 22q11.2 DS and demonstrate how facial analysis technology can assist clinicians in making accurate 22q11.2 DS diagnoses. This work will assist in earlier detection and in increasing recognition of 22q11.2 DS throughout the world. © 2017 Wiley Periodicals, Inc.

  17. Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kailang; Li, Weikai; Peng, Guiqing; Li, Fang; (Harvard-Med); (UMM-MED)

    2010-03-04

    NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel {beta}-sandwich core structure consisting of 2 layers of {beta}-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a 'virus-binding hotspot' on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions.

  18. A Rule-Based System Implementing a Method for Translating FOL Formulas into NL Sentences

    Science.gov (United States)

    Mpagouli, Aikaterini; Hatzilygeroudis, Ioannis

    In this paper, we mainly present the implementation of a system that translates first order logic (FOL) formulas into natural language (NL) sentences. The motivation comes from an intelligent tutoring system teaching logic as a knowledge representation language, where it is used as a means for feedback to the students-users. FOL to NL conversion is achieved by using a rule-based approach, where we exploit the pattern matching capabilities of rules. So, the system consists of rule-based modules corresponding to the phases of our translation methodology. Facts are used in a lexicon providing lexical and grammatical information that helps in producing the NL sentences. The whole system is implemented in Jess, a java-implemented rule-based programming tool. Experimental results confirm the success of our choices.

  19. Psychometric properties and validity of the Dutch Inventory of Personality Organization (IPO-NL).

    Science.gov (United States)

    Berghuis, Han; Kamphuis, Jan H; Boedijn, Gerard; Verheul, Roel

    2009-01-01

    This study investigated the psychometric qualities and validity of a Dutch translation of the Inventory of Personality Organization (IPO-NL) in a heterogeneous sample of 371 psychiatric patients and a sample of 181 normal controls. Results show good internal consistency and test-retest reliability. Exploratory factor analyses did not replicate its proposed five-factor structure, but suggested a four-factor structure instead. The IPO-NL appeared to have good concurrent validity across populations, and good convergent validity in terms of associations with measures of psychological distress and personality pathology severity. Taken together, the IPO-NL appears to be a useful instrument for evaluating general personality pathology for clinical practice. Future studies may further articulate its proposed subscales.

  20. Protein crystallization in a 100 nl solution with new stirring equipment

    International Nuclear Information System (INIS)

    Maki, S.; Murai, R.; Yoshikawa, H. Y.; Kitatani, T.; Nakata, S.; Kawahara, H.; Hasenaka, H.; Kobayashi, A.; Okada, S.; Sugiyama, S.; Adachi, H.; Matsumura, H.; Takano, K.; Murakami, S.; Inoue, T.; Sasaki, T.; Mori, Y.

    2008-01-01

    To investigate quantitatively the effects of stirring on protein crystallization, a new stirring system which can agitate a protein solution, ∼100 nl, by providing Hagen–Poiseuille flow has been successfully developed. To investigate quantitatively the effects of stirring on protein crystallization, a new stirring system which can agitate a protein solution, ∼100 nl, by providing Hagen–Poiseuille flow has been successfully developed. In addition, this new stirring system provides flow with a well defined pattern and velocity. Using this system, hen egg-white lysozyme was crystallized in 100–200 nl solutions while being stirred. The optimum stirring conditions for lysozyme crystals have been explored by evaluating the Reynolds (Re) number and the crystals obtained. Intermittent flow, as well as a low Re number, was found to contribute significantly to the growth of a smaller number of larger crystals

  1. Neuroradiographic findings in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Bohm, Lauren A; Zhou, Tom C; Mingo, Tyler J; Dugan, Sarah L; Patterson, Richard J; Sidman, James D; Roby, Brianne B

    2017-08-01

    22q11.2 deletion syndrome (22q11.2DS) is a common genetic disorder with enormous phenotypic heterogeneity. Despite the established prevalence of developmental and neuropsychiatric issues in this syndrome, its neuroanatomical correlates are not as well understood. A retrospective chart review was performed on 111 patients diagnosed with 22q11.2DS. Of the 111 patients, 24 with genetically confirmed 22q11.2 deletion and brain MRI or MRA were included in this study. The most common indications for imaging were unexplained developmental delay (6/24), seizures of unknown etiology (5/24), and unilateral weakness (3/24). More than half (13/24) of the patients had significant radiographic findings, including persistent cavum septi pellucidi and/or cavum vergae (8/24), aberrant cortical veins (6/24), polymicrogyria or cortical dysplasia (4/24), inner ear deformities (3/24), hypoplastic internal carotid artery (2/24), and hypoplastic cerebellum (1/24). These findings reveal the types and frequencies of brain malformations in this case series, and suggest that the prevalence of neuroanatomical abnormalities in 22q11.2DS may be underestimated. Understanding indications for imaging and frequently encountered brain malformations will result in early diagnosis and intervention in an effort to optimize patient outcomes. © 2017 Wiley Periodicals, Inc.

  2. 18 CFR 11.2 - Use of government lands.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Use of government lands... ACT Charges for Costs of Administration, Use of Tribal Lands and Other Government Lands, and Use of Government Dams § 11.2 Use of government lands. (a) Reasonable annual charges for recompensing the United...

  3. Concurrent microdeletion and duplication of 22q11.2.

    Science.gov (United States)

    Blennow, E; Lagerstedt, K; Malmgren, H; Sahlén, S; Schoumans, J; Anderlid, Bm

    2008-07-01

    Microduplication of 22q11.2 has been reported in fewer than 40 cases, all of them including the DiGeorge critical region (DGCR). We here present the characterization of a new duplication that does not include the DGCR. The duplication was initially found by multiplex ligation-dependent probe amplification analysis of 22q11.2 in a young girl with a concurrent deletion of the DGCR in 70% of her peripheral blood lymphocytes. Her phenotype included many of the features of the velocardiofacial syndrome, with velopharyngeal insufficiency, recurrent infections, learning and concentration problems as well as difficulties in social interactions. However, there were no congenital malformations, and her facial appearance was not typical for the syndrome. Further investigations included array comparative genomic hybridization (CGH) to size map the deletion/duplication and interphase fluorescent in situ hybridization to investigate mosaicism and the structure of the rearrangement. An identical duplication of this part of 22q11.2 has not been reported before, and the duplication itself seems to be associated with very mild or no symptoms. This study contributes to the growing knowledge regarding new deletions and duplications of 22q11.2, most of them mediated by the pre-disposing high number of low-copy repeats in the region.

  4. Genetic Counseling for the 22q11.2 Deletion

    Science.gov (United States)

    McDonald-McGinn, Donna M.; Zackai, Elaine H.

    2008-01-01

    Because of advances in palliative medical care, children with the 22q11.2 deletion syndrome are surviving into adulthood. An increase in reproductive fitness will likely follow necessitating enhanced access to genetic counseling for these patients and their families. Primary care physicians/obstetric practitioners are in a unique position to…

  5. Executive functioning in college students: Evaluation of the Dutch Executive Function Index (EFI-NL)

    NARCIS (Netherlands)

    Janssen, G.T.L.; Mey, H.R.A. De; Egger, J.I.M.

    2009-01-01

    The Executive Function Index (EFI) is a short self-report questionnaire for the assessment of executive functions (EF) as encountered in daily life. The aim of the present study is to examine the psychometric properties of the Dutch version of the EFI (EFI-NL) in a college student sample (N = 376).

  6. UltiMatch-NL: a Web service matchmaker based on multiple semantic filters.

    Science.gov (United States)

    Mohebbi, Keyvan; Ibrahim, Suhaimi; Zamani, Mazdak; Khezrian, Mojtaba

    2014-01-01

    In this paper, a Semantic Web service matchmaker called UltiMatch-NL is presented. UltiMatch-NL applies two filters namely Signature-based and Description-based on different abstraction levels of a service profile to achieve more accurate results. More specifically, the proposed filters rely on semantic knowledge to extract the similarity between a given pair of service descriptions. Thus it is a further step towards fully automated Web service discovery via making this process more semantic-aware. In addition, a new technique is proposed to weight and combine the results of different filters of UltiMatch-NL, automatically. Moreover, an innovative approach is introduced to predict the relevance of requests and Web services and eliminate the need for setting a threshold value of similarity. In order to evaluate UltiMatch-NL, the repository of OWLS-TC is used. The performance evaluation based on standard measures from the information retrieval field shows that semantic matching of OWL-S services can be significantly improved by incorporating designed matching filters.

  7. Possible involvement of infection with human coronavirus 229E, but not NL63, in Kawasaki disease.

    Science.gov (United States)

    Shirato, Kazuya; Imada, Yoshio; Kawase, Miyuki; Nakagaki, Keiko; Matsuyama, Shutoku; Taguchi, Fumihiro

    2014-12-01

    Although human coronavirus (HCoV)-NL63 was once considered a possible causative agent of Kawasaki disease based on RT-PCR analyses, subsequent studies could not confirm the result. In this study, this possibility was explored using serological tests. To evaluate the role of HCoV infection in patients with Kawasaki disease, immunofluorescence assays and virus neutralizing tests were performed. Paired serum samples were obtained from patients with Kawasaki disease who had not been treated with γ-globulin. HCoV-NL63 and two antigenically different isolates of HCoV-229E (ATCC-VR740 and a new isolate, Sendai-H) were examined as controls. Immunofluorescence assays detected no difference in HCoV-NL63 antibody positivity between the patients with Kawasaki disease and controls, whereas the rate of HCoV-229E antibody positivity was higher in the patients with Kawasaki disease than that in controls. The neutralizing tests revealed no difference in seropositivity between the acute and recovery phases of patients with Kawasaki disease for the two HCoV-229Es. However, the Kawasaki disease specimens obtained from patients in recovery phase displayed significantly higher positivity for Sendai-H, but not for ATCC-VR740, as compared to the controls. The serological test supported no involvement of HCoV-NL63 but suggested the possible involvement of HCoV-229E in the development of Kawasaki disease. © 2014 Wiley Periodicals, Inc.

  8. The dominance of human coronavirus OC43 and NL63 infections in infants

    NARCIS (Netherlands)

    Dijkman, Ronald; Jebbink, Maarten F.; Gaunt, Eleanor; Rossen, John W. A.; Templeton, Kate E.; Kuijpers, Taco W.; van der Hoek, Lia

    2012-01-01

    Background: It is unknown to what extent the human coronaviruses (HCoVs) OC43, HKU1, 229E and NL63 infect healthy children. Frequencies of infections are only known for hospitalized children. Objectives: Comparing infection frequencies in children who have mild infections with frequencies in

  9. Prenatal diagnosis of interstitial deletion of 17(p11.2p11.2) (Smith-Magenis Syndrome)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-01-15

    Interstitial deletion of 17p11.2 is associated with Smith-Magenis syndrome. This is a recognizable chromosomal deletion syndrome, characterized by brachycephaly, midface hypoplasia, growth and mental retardation, behavioral problems, and ocular abnormalities. Molecular analysis indicates it is a contiguous gene syndrome. Over 50 patients have been reported since the deletion was first described by Smith et al. [1982]. Cases include one with mosaicism and a familial example. None were prenatally diagnosed. The authors report on the prenatal detection of interstitial deletion of 17p11.2. 11 refs., 1 fig.

  10. Developmental trajectories in 22q11.2 deletion.

    Science.gov (United States)

    Swillen, Ann; McDonald-McGinn, Donna

    2015-06-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic condition, is the most common microdeletion syndrome affecting 1 in 2,000-4,000 live births and involving haploinsufficiency of ∼50 genes resulting in a multisystem disorder. Phenotypic expression is highly variable and ranges from severe life-threatening conditions to only a few associated features. Most common medical problems include: congenital heart disease, in particular conotruncal anomalies; palatal abnormalities, most frequently velopharyngeal incompetence (VPI); immunodeficiency; hypocalcemia due to hypoparathyroidism; genitourinary anomalies; severe feeding/gastrointestinal differences; and subtle dysmorphic facial features. The neurocognitive profile is also highly variable, both between individuals and during the course of development. From infancy onward, motor delays (often with hypotonia) and speech/language deficits are commonly observed. During the preschool and primary school ages, learning difficulties are very common. The majority of patients with 22q11.2DS have an intellectual level that falls in the borderline range (IQ 70-84), and about one-third have mild to moderate intellectual disability. More severe levels of intellectual disability are uncommon in children and adolescents but are more frequent in adults. Individuals with 22q11.2DS are at an increased risk for developing several psychiatric disorders including attention deficit with hyperactivity disorder (ADHD), autism spectrum disorder (ASD), anxiety and mood disorders, and psychotic disorders and schizophrenia. In this review, we will focus on the developmental phenotypic transitions regarding cognitive development in 22q11.2DS from early preschool to adulthood, and on the changing behavioral/psychiatric phenotype across age, on a background of frequently complex medical conditions. © 2015 Wiley Periodicals, Inc.

  11. Developmental Trajectories in 22q11.2 Deletion

    Science.gov (United States)

    Swillen, Ann; McDonald-McGinn, Donna M.

    2016-01-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic condition, is the most common microdeletion syndrome affecting 1 in 2,000–4,000 live births and involving haploinsufficiency of ∼50 genes resulting in a multisystem disorder. Phenotypic expression is highly variable and ranges from severe life-threatening conditions to only a few associated features. Most common medical problems include: congenital heart disease, in particular conotruncal anomalies; palatal abnormalities, most frequently velopharyngeal incompetence (VPI); immunodeficiency; hypocalcemia due to hypoparathyroidism; genitourinary anomalies; severe feeding/gastrointestinal differences; and subtle dysmorphic facial features. The neurocognitive profile is also highly variable, both between individuals and during the course of development. From infancy onward, motor delays (often with hypotonia) and speech/language deficits are commonly observed. During the preschool and primary school ages, learning difficulties are very common. The majority of patients with 22q11.2DS have an intellectual level that falls in the borderline range (IQ 70–84), and about one-third have mild to moderate intellectual disability. More severe levels of intellectual disability are uncommon in children and adolescents but are more frequent in adults. Individuals with 22q11.2DS are at an increased risk for developing several psychiatric disorders including attention deficit with hyperactivity disorder (ADHD), autism spectrum disorder (ASD), anxiety and mood disorders, and psychotic disorders and schizophrenia. In this review, we will focus on the developmental phenotypic transitions regarding cognitive development in 22q11.2DS from early preschool to adulthood, and on the changing behavioral/psychiatric phenotype across age, on a background of frequently complex medical conditions. PMID:25989227

  12. Plaque assay for human coronavirus NL63 using human colon carcinoma cells

    Directory of Open Access Journals (Sweden)

    Drosten Christian

    2008-11-01

    Full Text Available Abstract Background Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. Results 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2 replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2. CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4th day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. Conclusion CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.

  13. Correlation and relativistic effects for the 4f-nl and 5p-nl multipole transitions in Er-like tungsten

    International Nuclear Information System (INIS)

    Safronova, U. I.; Safronova, A. S.

    2011-01-01

    Wavelengths, transition rates, and line strengths are calculated for the multipole (E1, M1, E2, M2, E3, and M3) transitions between the excited [Cd]4f 13 5p 6 nl, [Cd]4f 14 5p 5 nl configurations and the ground [Cd]4f 14 5p 6 state in Er-like W 6+ ion ([Cd]=[Kr]4d 10 5s 2 ). In particular, the relativistic many-body perturbation theory (RMBPT), including the Breit interaction, is used to evaluate energies and transition rates for multipole transitions in this hole-particle system. This method is based on the relativistic many-body perturbation theory that agrees with multiconfiguration Dirac-Fock (MCDF) calculations in lowest order, and includes all second-order correlation corrections and corrections from negative-energy states. The calculations start from a [Cd]4f 14 5p 6 Dirac-Fock (DF) potential. First-order perturbation theory is used to obtain intermediate-coupling coefficients, and second-order RMBPT is used to determine the multipole matrix elements needed for calculations of other atomic properties such as line strengths and transition rates. In addition, core multipole polarizability is evaluated in random-phase and DF approximations. The comparison with available data is demonstrated.

  14. Impacts of future changes on groundwater recharge and flow in highly-connected river-aquifer systems: A case study of the Spokane Valley-Rathdrum Prairie Aquifer

    Science.gov (United States)

    Nguyen, T. T.; Baxter, H.; Barber, M. E.; Hossain, A.; Orr, C. H.; Adam, J. C.

    2013-12-01

    The Spokane, Washington-Coeur d'Alene, Idaho Corridor is well-known for its Spokane Valley-Rathdrum Prairie (SVRP) Aquifer which is a sole source of drinking water for more than 500,000 people. The aquifer is highly connected to the Spokane River and responds very fast to natural and human perturbations, making it relatively vulnerable to climate and anthropogenic changes in future decades. Recent studies have indicated a decline in minimum daily flow in the Spokane River in the last 100 years, while projecting an increase in cool-season precipitation into the future. We investigated the potential impacts of these projected future climate-driven hydrologic changes on groundwater recharge and flow in the SVRP. A distributed, physically-based hydrological model, the Precipitation Runoff Modeling System (PRMS), was coupled with an existing Modular three-dimensional finite-difference ground-water model (MODFLOW) to have better estimates of recharge into the SVRP as well as the interaction of surface water and groundwater. The couple model was calibrated and validated at a daily time-step within the Model-Independent Parameter Estimation (PEST) framework using 16 years of both observed streamflow and observed well data (1990 - 2005). To assess future climate change impacts, statistically downscaled climate projections of temperature and precipitation between 2010 and 2050 from four general circulation models were used. The results from the coupled model provide insight on the interplay between snowmelt, streamflow, groundwater recharge and discharge in such a highly-connected system. Moreover, the relative sensitivities of groundwater recharge and flow with respect to changes in climate and land cover are also examined. These results can be used as good references for long term water resources management and planning in the region.

  15. Confirmatory Factor Analysis of the Dutch Version of the Wechsler Memory Scale-Fourth Edition (WMS-IV-NL)

    NARCIS (Netherlands)

    Bouman, Z.; Hendriks, M.P.; Kerkmeer, M.C.; Kessels, R.P.C.; Aldenkamp, A.P.

    2015-01-01

    The latent factor structure of the Dutch version of the Wechsler Memory Scale-Fourth Edition (WMS-IV-NL) was examined with a series of confirmatory factor analyses. As part of the Dutch standardization, 1,188 healthy participants completed the WMS-IV-NL. Four models were tested for the Adult Battery

  16. Automated Generation of OCL Constraints: NL based Approach vs Pattern Based Approach

    Directory of Open Access Journals (Sweden)

    IMRAN SARWAR BAJWA

    2017-04-01

    Full Text Available This paper presents an approach used for automated generations of software constraints. In this model, the SBVR (Semantics of Business Vocabulary and Rules based semi-formal representation is obtained from the syntactic and semantic analysis of a NL (Natural Language (such as English sentence. A SBVR representation is easy to translate to other formal languages as SBVR is based on higher-order logic like other formal languages such as OCL (Object Constraint Language. The proposed model endows with a systematic and powerful system of incorporating NL knowledge on the formal languages. A prototype is constructed in Java (an Eclipse plug-in as a proof of the concept. The performance was tested for a few sample texts taken from existing research thesis reports and books

  17. How to Assist Formalization of NL Regulations: Lessons from Business Rules Acquisition Experiments

    OpenAIRE

    Nazarenko , Adeline

    2013-01-01

    International audience; Decision systems usually rely on a set of business rules that describe the expected behavior of a system or an organization and that determine the decisions to be taken in different situations. However, rule acquisition is often the bottleneck that hinders the development of decision systems. When these rules are based on regulations written in Natural Language (NL), one solution is to derive formal business rules from the source documents. This approach also allows ch...

  18. Wbp2nl has a developmental role in establishing neural and non-neural ectodermal fates.

    Science.gov (United States)

    Marchak, Alexander; Grant, Paaqua A; Neilson, Karen M; Datta Majumdar, Himani; Yaklichkin, Sergey; Johnson, Diana; Moody, Sally A

    2017-09-01

    In many animals, maternally synthesized mRNAs are critical for primary germ layer formation. In Xenopus, several maternal mRNAs are enriched in the animal blastomere progenitors of the embryonic ectoderm. We previously identified one of these, WW-domain binding protein 2 N-terminal like (wbp2nl), that others previously characterized as a sperm protein (PAWP) that promotes meiotic resumption. Herein we demonstrate that it has an additional developmental role in regionalizing the embryonic ectoderm. Knock-down of Wbp2nl in the dorsal ectoderm reduced cranial placode and neural crest gene expression domains and expanded neural plate domains; knock-down in ventral ectoderm reduced epidermal gene expression. Conversely, increasing levels of Wbp2nl in the neural plate induced ectopic epidermal and neural crest gene expression and repressed many neural plate and cranial placode genes. The effects in the neural plate appear to be mediated, at least in part, by down-regulating chd, a BMP antagonist. Because the cellular function of Wbp2nl is not known, we mutated several predicted motifs. Expressing mutated proteins in embryos showed that a putative phosphorylation site at Thr45 and an α-helix in the PH-G domain are required to ectopically induce epidermal and neural crest genes in the neural plate. An intact YAP-binding motif also is required for ectopic epidermal gene expression as well as for down-regulating chd. This work reveals novel developmental roles for a cytoplasmic protein that promotes epidermal and neural crest formation at the expense of neural ectoderm. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Chromosome 22q11.2 microdeletion syndrome.

    Science.gov (United States)

    Molesky, Marion G

    2011-01-01

    Chromosome 22q11.2 microdeletion syndrome is the most common microdeletion syndrome in humans. It involves the loss of genetic material on the short arm of one of the chromosome 22 alleles. Until advanced testing was available, this syndrome was known by various names including DiGeorge syndrome and velo-cardio-facial syndrome. This syndrome has a varied presentation with significant abnormalities including congenital heart disease, hypocalcemia, immunologic deficiencies, learning disabilities, and behavioral problems. A multidisciplinary approach is required to diagnose and manage the varied manifestations.

  20. Hematological abnormalities and 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano Machado Rosa

    2011-01-01

    Full Text Available The 22q11.2 deletion syndrome (22q11DS is a common genetic disease characterized by broad phenotypic variability. Despite the small number of studies describing hematological alterations in individuals with 22q11DS, it appears that these abnormalities are more frequent than previously imagined. Thus, the objective of our study was to report on a patient with 22q11DS presenting thrombocytopenia and large platelets and to review the literature. The patient, a 13-year-old boy, was originally evaluated due to craniofacial dysmorphia and speech delay. He also had a history of behavioral changes, neuropsychomotor delay and recurrent otitis/sinusitis. The identification of a 22q11.2 microdeletion by fluorescent in situ hybridization diagnosed the syndrome. Despite his hematological alterations, he only had a history of epistaxis and bruising of the upper and lower limbs. Assessments of the prothrombin time, thrombin time, partial thromboplastin time, bleeding time, fibrinogen levels and platelet aggregation (including the ristocetin induced platelet aggregation test were all normal. Hematological alterations observed in 22q11DS are directly related to the genetic disorder itself (especially in respect to deletion of the GPIb gene and secondary to some clinical findings, such as immunodeficiency. Macrothrombocytopenia is increasingly being considered a feature of the broad spectrum of 22q11DS and may potentially be a clinical marker for the syndrome.

  1. Reduction in open field activity in the absence of memory deficits in the AppNL-G-F knock-in mouse model of Alzheimer's disease.

    Science.gov (United States)

    Whyte, Lauren S; Hemsley, Kim M; Lau, Adeline A; Hassiotis, Sofia; Saito, Takashi; Saido, Takaomi C; Hopwood, John J; Sargeant, Timothy J

    2018-01-15

    The recent development of knock-in mouse models of Alzheimer's disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer's researchers are the App NL-F and App NL-G-F mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of App NL-G-F/NL-G-F (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between App NL-G-F/NL-G-F and wild-type mice. Further assessment of these mice using the novel object recognition test and Morris water maze also revealed no differences between App NL-G-F/NL-G-F and wild-type mice. Despite a lack of demonstrated cognitive deficits, we report a reduction in locomotor/exploratory activity in an open field. Histological examination of App NL-G-F/NL-G-F mice showed widespread distribution of amyloid plaques at this age. We conclude that whilst at six-months of age, memory deficits are not sufficiently robust to be replicated in varying environments, amyloid plaque burden is significant in App NL-G-F/NL-G-F knock-in brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Validation of the Dutch language version of the Safety Attitudes Questionnaire (SAQ-NL).

    Science.gov (United States)

    Haerkens, Marck Htm; van Leeuwen, Wouter; Sexton, J Bryan; Pickkers, Peter; van der Hoeven, Johannes G

    2016-08-15

    As the first objective of caring for patients is to do no harm, patient safety is a priority in delivering clinical care. An essential component of safe care in a clinical department is its safety climate. Safety climate correlates with safety-specific behaviour, injury rates, and accidents. Safety climate in healthcare can be assessed by the Safety Attitudes Questionnaire (SAQ), which provides insight by scoring six dimensions: Teamwork Climate, Job Satisfaction, Safety Climate, Stress Recognition, Working Conditions and Perceptions of Management. The objective of this study was to assess the psychometric properties of the Dutch language version of the SAQ in a variety of clinical departments in Dutch hospitals. The Dutch version (SAQ-NL) of the SAQ was back translated, and analyzed for semantic characteristics and content. From October 2010 to November 2015 SAQ-NL surveys were carried out in 17 departments in two university and seven large non-university teaching hospitals in the Netherlands, prior to a Crew Resource Management human factors intervention. Statistical analyses were used to examine response patterns, mean scores, correlations, internal consistency reliability and model fit. Cronbach's α's and inter-item correlations were calculated to examine internal consistency reliability. One thousand three hundred fourteen completed questionnaires were returned from 2113 administered to health care workers, resulting in a response rate of 62 %. Confirmatory Factor Analysis revealed the 6-factor structure fit the data adequately. Response patterns were similar for professional positions, departments, physicians and nurses, and university and non-university teaching hospitals. The SAQ-NL showed strong internal consistency (α = .87). Exploratory analysis revealed differences in scores on the SAQ dimensions when comparing different professional positions, when comparing physicians to nurses and when comparing university to non-university hospitals. The SAQ-NL

  3. Epilepsy and chromosomal rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)].

    Science.gov (United States)

    Goldman, Alica M; Potocki, Lorraine; Walz, Katherina; Lynch, Jennifer K; Glaze, Daniel G; Lupski, James R; Noebels, Jeffrey L

    2006-02-01

    Smith-Magenis syndrome is a multiple congenital anomalies/mental retardation syndrome associated with a heterozygous deletion of chromosome 17p11.2. Seizures have not been formally studied in this population. Our objectives were to estimate the prevalence of seizures and electroencephalographic (EEG) epileptiform abnormalities in patients with Smith-Magenis syndrome with defined chromosomal rearrangements and to describe the spectrum of abnormal EEG patterns. Prolonged video-EEGs were obtained in 60 patients. Eighteen percent of patients reported a seizure history; however, abnormal EEGs were identified in 31 of the 60 subjects and 27 of 31 were epileptiform. Generalized epileptiform patterns were the most common (73%). Most patients with either small or large deletions had an abnormal EEG (83%; 75%) in contrast to those with a common deletion (49%). Our results indicate that epileptiform EEG abnormalities are frequent in patients with Smith-Magenis syndrome. Considering that close to one third of individuals with Smith-Magenis syndrome with epileptiform abnormalities also had a history of clinical seizures, cortical hyperexcitability and epilepsy should be considered an important component of the Smith-Magenis syndrome clinical phenotype.

  4. Outcomes of senior reach gatekeeper referrals: comparison of the Spokane gatekeeper program, Colorado Senior Reach, and Mid-Kansas Senior Outreach.

    Science.gov (United States)

    Bartsch, David A; Rodgers, Vicki K; Strong, Don

    2013-01-01

    Outcomes of older adults referred for care management and mental health services through the senior reach gatekeeper model of case finding were examined in this study and compared with the Spokane gatekeeper model Colorado Senior Reach and the Mid-Kansas Senior Outreach (MKSO) programs are the two Senior Reach Gatekeeper programs modeled after the Spokane program, employing the same community education and gatekeeper model and with mental health treatment for elderly adults in need of support. The three mature programs were compared on seniors served isolation, and depression ratings. Nontraditional community gatekeepers were trained and referred seniors in need. Findings indicate that individuals served by the two Senior Reach Gatekeeper programs demonstrated significant improvements. Isolation indicators such as social isolation decreased and depression symptoms and suicide ideation also decreased. These findings for two Senior Reach Gatekeeper programs demonstrate that the gatekeeper approach to training community partners worked in referring at-risk seniors in need in meeting their needs, and in having a positive impact on their lives.

  5. Evidence supporting a zoonotic origin of human coronavirus strain NL63.

    Science.gov (United States)

    Huynh, Jeremy; Li, Shimena; Yount, Boyd; Smith, Alexander; Sturges, Leslie; Olsen, John C; Nagel, Juliet; Johnson, Joshua B; Agnihothram, Sudhakar; Gates, J Edward; Frieman, Matthew B; Baric, Ralph S; Donaldson, Eric F

    2012-12-01

    The relationship between bats and coronaviruses (CoVs) has received considerable attention since the severe acute respiratory syndrome (SARS)-like CoV was identified in the Chinese horseshoe bat (Rhinolophidae) in 2005. Since then, several bats throughout the world have been shown to shed CoV sequences, and presumably CoVs, in the feces; however, no bat CoVs have been isolated from nature. Moreover, there are very few bat cell lines or reagents available for investigating CoV replication in bat cells or for isolating bat CoVs adapted to specific bat species. Here, we show by molecular clock analysis that alphacoronavirus (α-CoV) sequences derived from the North American tricolored bat (Perimyotis subflavus) are predicted to share common ancestry with human CoV (HCoV)-NL63, with the most recent common ancestor between these viruses occurring approximately 563 to 822 years ago. Further, we developed immortalized bat cell lines from the lungs of this bat species to determine if these cells were capable of supporting infection with HCoVs. While SARS-CoV, mouse-adapted SARS-CoV (MA15), and chimeric SARS-CoVs bearing the spike genes of early human strains replicated inefficiently, HCoV-NL63 replicated for multiple passages in the immortalized lung cells from this bat species. These observations support the hypothesis that human CoVs are capable of establishing zoonotic-reverse zoonotic transmission cycles that may allow some CoVs to readily circulate and exchange genetic material between strains found in bats and other mammals, including humans.

  6. Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma-specific t(X;18)(p11.2;q11.2) breakpoint

    NARCIS (Netherlands)

    de Leeuw, B; Berger, W; Sinke, R J; Suijkerbuijk, R F; Gilgenkrantz, S; Geraghty, M T; Valle, D; Monaco, A P; Lehrach, H; Ropers, H H

    A somatic cell hybrid containing the synovial sarcoma-associated t(X;18)(p11.2;q11.2) derivative (der(X)) chromosome was used to characterize the translocation breakpoint region on the X chromosome. By using Southern hybridization of DNA from this der(X) hybrid in conjunction with Xp-region specific

  7. Prevalence of 22q11.2 microdeletion syndrome in Iranian patients with cleft palate

    Directory of Open Access Journals (Sweden)

    Narges Nouri

    2016-01-01

    Conclusion: It seems that SMCP or VPI, in addition to one or more another features of 22q11.2 deletions, especially developmental delay, may be good criteria for molecular investigation of 22q11.2 region.

  8. Candidate Genes and the Behavioral Phenotype in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Prasad, Sarah E.; Howley, Sarah; Murphy, Kieran C.

    2008-01-01

    There is an overwhelming evidence that children and adults with 22q11.2 deletion syndrome (22q11.2DS) have a characteristic behavioral phenotype. In particular, there is a growing body of evidence that indicates an unequivocal association between 22q11.2DS and schizophrenia, especially in adulthood. Deletion of 22q11.2 is the third highest risk…

  9. Prevalence of 22q11.2 microdeletion syndrome in Iranian patients with cleft palate

    OpenAIRE

    Nouri, Narges; Memarzadeh, Mehrdad; Salehi, Mansoor; Nouri, Nayereh; Meamar, Rokhsareh; Behnam, Mahdiyeh; Derakhshandeh, Fatemeh; Kashkoolinejad, Tahereh; Abdali, Hossein

    2016-01-01

    Background: 22q11.2 microdeletion syndrome is the most common multiple genetic disorder associated with learning disabilities, developmental delays, immune deficiency, hypocalcemia, and cleft palate. Finding some valid criteria for screening of 22q11.2 deletion syndromes in infants would be very helpful in early diagnosis and treatment. Materials and Methods: Since 69% of individuals with 22q11.2 deletion have a palatal abnormality, we studied the prevalence of 22q11.2 deletion syndrome in...

  10. A Novel Pseudo-Dicentric Variant of 16p11.2-q11.2 Contains Euchromatin from 16p11.2-p11.1 and Resembles Pathogenic Duplications of Proximal 16q

    DEFF Research Database (Denmark)

    Barber, J C K; Brasch-Andersen, Charlotte; Maloney, V K

    2012-01-01

    ) and oligonucleotide array comparative genomic hybridization (oaCGH) were used to show that these bands contained a euchromatic duplication of a minimum of 940 kb between base pairs 34,197,413-35,137,025 in 16p11.2-p11.1 as well as a duplication of the centromere and major 16qh/16p11.2 heterochromatic block, covering...

  11. Movement disorders and other motor abnormalities in adults with 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Boot, Erik; Butcher, Nancy J.; van Amelsvoort, Thérèse A. M. J.; Lang, Anthony E.; Marras, Connie; Pondal, Margarita; Andrade, Danielle M.; Fung, Wai Lun Alan; Bassett, Anne S.

    2015-01-01

    Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In

  12. Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

    Science.gov (United States)

    Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

    2014-01-01

    Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…

  13. Risk of malignancy in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Stevens, Toer; van der Werff Ten Bosch, Jutte; De Rademaeker, Marjan; Van Den Bogaert, Ann; van den Akker, Machiel

    2017-04-01

    22q11.2DS is a significant health problem because of its fairly high incidence. It is relevant to be vigilant regarding the diagnosis of cancer amongst 22q11.2 patients as there might be an increased risk, especially amongst patients with the 22q11.2 distal deletion syndrome.

  14. Ras Labs.-CASIS-ISS NL experiment for synthetic muscle: resistance to ionizing radiation

    Science.gov (United States)

    Rasmussen, Lenore; Sandberg, Eric; Albers, Leila N.; Rodriguez, Simone; Gentile, Charles A.; Meixler, Lewis D.; Ascione, George; Hitchner, Robert; Taylor, James; Hoffman, Dan; Cylinder, David; Moy, Leon; Mark, Patrick S.; Prillaman, Daniel L.; Nordarse, Robert; Menegus, Michael J.; Ratto, Jo Ann; Thellen, Christopher; Froio, Danielle; Furlong, Cosme; Razavi, Payam; Valenza, Logan; Hablani, Surbhi; Fuerst, Tyler; Gallucci, Sergio; Blocher, Whitney; Liffland, Stephanie

    2016-04-01

    In anticipation of deep space travel, new materials are being explored to assist and relieve humans in dangerous environments, such as high radiation, extreme temperature, and extreme pressure. Ras Labs Synthetic Muscle - electroactive polymers (EAPs) that contract and expand at low voltages - which mimic the unique gentle-yet-strong nature of human tissue, is a potential asset to manned space travel through protective gear and human assist robotics and for unmanned space exploration through deep space. Generation 3 Synthetic Muscle was proven to be resistant to extreme temperatures, and there were indications that these materials may also be radiation resistant. The purpose of the Ras Labs-CASIS-ISS Experiment is to test the radiation resistivity of the third and fourth generation of these EAPs, as well as to make them even more radiation resistant or radiation hardened. On Earth, exposure of the Generation 3 and Generation 4 EAPs to a Cs-137 radiation source for 47.8 hours with a total dose of 305.931 kRad of gamma radiation was performed at the US Department of Energy's Princeton Plasma Physics Laboratory (PPPL) at Princeton University, followed by pH, peroxide, Shore Hardness Durometry, and electroactivity testing to determine the inherent radiation resistivity of these contractile EAPs and to determine whether the EAPs could be made even more radiation resistant through the application of appropriate additives and coatings. The on Earth preliminary tests determined that selected Ras Labs EAPs were not only inherently radiation resistant, but with the appropriate coatings and additives, could be made even more radiation resistant. Gforce testing to over 10 G's was performed at US Army's ARDEC Labs, with excellent results, in preparation for space flight to the International Space Station National Laboratory (ISS-NL). Selected samples of Generation 3 and Generation 4 Synthetic Muscle™, with various additives and coatings, were launched to the ISS-NL on April

  15. Deletion size analysis of 1680 22q11.2DS subjects identifies a new recombination hotspot on chromosome 22q11.2.

    Science.gov (United States)

    Guo, Tingwei; Diacou, Alexander; Nomaru, Hiroko; McDonald-McGinn, Donna M; Hestand, Matthew; Demaerel, Wolfram; Zhang, Liangtian; Zhao, Yingjie; Ujueta, Francisco; Shan, Jidong; Montagna, Cristina; Zheng, Deyou; Crowley, Terrence B; Kushan-Wells, Leila; Bearden, Carrie E; Kates, Wendy R; Gothelf, Doron; Schneider, Maude; Eliez, Stephan; Breckpot, Jeroen; Swillen, Ann; Vorstman, Jacob; Zackai, Elaine; Benavides Gonzalez, Felipe; Repetto, Gabriela M; Emanuel, Beverly S; Bassett, Anne S; Vermeesch, Joris R; Marshall, Christian R; Morrow, Bernice E

    2018-04-01

    Recurrent, de novo, meiotic non-allelic homologous recombination events between low copy repeats, termed LCR22s, leads to the 22q11.2 deletion syndrome (22q11.2DS; velo-cardio-facial syndrome/DiGeorge syndrome). Although most 22q11.2DS patients have a similar sized 3 million base pair (Mb), LCR22A-D deletion, some have nested LCR22A-B or LCR22A-C deletions. Our goal is to identify additional recurrent 22q11.2 deletions associated with 22q11.2DS, serving as recombination hotspots for meiotic chromosomal rearrangements. Here, using data from Affymetrix 6.0 microarrays on 1680 22q11.2DS subjects, we identified what appeared to be a nested proximal 22q11.2 deletion in 38 (2.3%) of them. Using molecular and haplotype analyses from 14 subjects and their parent(s) with available DNA, we found essentially three types of scenarios to explain this observation. In eight subjects, the proximal breakpoints occurred in a small sized 12 kb LCR distal to LCR22A, referred to LCR22A+, resulting in LCR22A+-B or LCR22A+-D deletions. Six of these eight subjects had a nested 22q11.2 deletion that occurred during meiosis in a parent carrying a benign 0.2 Mb duplication of the LCR22A-LCR22A+ region with a breakpoint in LCR22A+. Another six had a typical de novo LCR22A-D deletion on one allele and inherited the LCR22A-A+ duplication from the other parent thus appearing on microarrays to have a nested deletion. LCR22A+ maps to an evolutionary breakpoint between mice and humans and appears to serve as a local hotspot for chromosome rearrangements on 22q11.2.

  16. Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome

    OpenAIRE

    Bassett, Anne S.; Marshall, Christian R.; Lionel, Anath C.; Chow, Eva W.C.; Scherer, Stephen W.

    2008-01-01

    22q11.2 Deletion Syndrome (22q11.2DS) is a common microdeletion syndrome with congenital and late-onset features. Testing for the genomic content of copy number variations (CNVs) may help elucidate the 22q11.2 deletion mechanism and the variable clinical expression of the syndrome including the high (25%) risk for schizophrenia. We used genome-wide microarrays to assess CNV content and the parental origin of 22q11.2 deletions in a cohort of 100 adults with 22q11.2DS (44 with schizophrenia) an...

  17. Confirmatory Factor Analysis of the Dutch Version of the Wechsler Memory Scale-Fourth Edition (WMS-IV-NL).

    Science.gov (United States)

    Bouman, Zita; Hendriks, Marc P H; Kerkmeer, Margreet C; Kessels, Roy P C; Aldenkamp, Albert P

    2015-05-01

    The latent factor structure of the Dutch version of the Wechsler Memory Scale-Fourth Edition (WMS-IV-NL) was examined with a series of confirmatory factor analyses. As part of the Dutch standardization, 1,188 healthy participants completed the WMS-IV-NL. Four models were tested for the Adult Battery (16-69 years; N = 699), and two models were tested for the Older Adult Battery (65-90 years; N = 489). Results corroborated the presence of three WMS-IV-NL factors in the Adult Battery consisting of Auditory Memory, Visual Memory, and Visual Working Memory. A two-factor model (consisting of Auditory Memory and Visual Memory) provided the best fit for the data of the Older Adult Battery. These findings provide evidence for the structural validity of the WMS-IV-NL, and further support the psychometric integrity of the WMS-IV. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Lifelong Learning and the E-Strategy of the Open University of the Netherlands: ou.nl

    NARCIS (Netherlands)

    Westera, Wim; Kalz, Marco

    2008-01-01

    Westera, W., & Kalz, M. (2008). Lifelong Learning and the E-Strategy of the Open University of the Netherlands: ou.nl. In J. Stratmann & M. Kerres (Eds.), E-strategy, Strategisches Informationsmanagement für Forschung und Lehre, Medien in de Wissenschaft Band 46 (pp. 253-266). Gesellschaft für

  19. Temporal stability of the Dutch version of the Wechsler Memory Scale - Fourth Edition (WMS-IV-NL)

    NARCIS (Netherlands)

    Bouman, Z.; Hendriks, M.P.H.; Aldenkamp, A.P.; Kessels, R.P.C.

    2015-01-01

    Objective: The Wechsler Memory Scale - Fourth Edition (WMS-IV) is one of the most widely used memory batteries. We examined the test–retest reliability, practice effects, and standardized regression-based (SRB) change norms for the Dutch version of the WMS-IV (WMS-IV-NL) after both short and long

  20. Association between lifestyle factors and quality-adjusted life years in the EPIC-NL cohort.

    Science.gov (United States)

    Fransen, Heidi P; May, Anne M; Beulens, Joline W J; Struijk, Ellen A; de Wit, G Ardine; Boer, Jolanda M A; Onland-Moret, N Charlotte; Hoekstra, Jeljer; van der Schouw, Yvonne T; Bueno-de-Mesquita, H Bas; Peeters, Petra H M

    2014-01-01

    The aim of our study was to relate four modifiable lifestyle factors (smoking status, body mass index, physical activity and diet) to health expectancy, using quality-adjusted life years (QALYs) in a prospective cohort study. Data of the prospective EPIC-NL study were used, including 33,066 healthy men and women aged 20-70 years at baseline (1993-7), followed until 31-12-2007 for occurrence of disease and death. Smoking status, body mass index, physical activity and adherence to a Mediterranean-style diet (excluding alcohol) were investigated separately and combined into a healthy lifestyle score, ranging from 0 to 4. QALYs were used as summary measure of healthy life expectancy, combining a person's life expectancy with a weight for quality of life when having a chronic disease. For lifestyle factors analyzed separately the number of years living longer in good health varied from 0.12 year to 0.84 year, after adjusting for covariates. A combination of the four lifestyle factors was positively associated with higher QALYs (P-trend healthy lifestyle score of 4 compared to a score of 0 was associated with almost a 2 years longer life in good health (1.75 QALYs [95% CI 1.37, 2.14]).

  1. Temporal Stability of the Dutch Version of the Wechsler Memory Scale-Fourth Edition (WMS-IV-NL).

    Science.gov (United States)

    Bouman, Zita; Hendriks, Marc P H; Aldenkamp, Albert P; Kessels, Roy P C

    2015-01-01

    The Wechsler Memory Scale-Fourth Edition (WMS-IV) is one of the most widely used memory batteries. We examined the test-retest reliability, practice effects, and standardized regression-based (SRB) change norms for the Dutch version of the WMS-IV (WMS-IV-NL) after both short and long retest intervals. The WMS-IV-NL was administered twice after either a short (M = 8.48 weeks, SD = 3.40 weeks, range = 3-16) or a long (M = 17.87 months, SD = 3.48, range = 12-24) retest interval in a sample of 234 healthy participants (M = 59.55 years, range = 16-90; 118 completed the Adult Battery; and 116 completed the Older Adult Battery). The test-retest reliability estimates varied across indexes. They were adequate to good after a short retest interval (ranging from .74 to .86), with the exception of the Visual Working Memory Index (r = .59), yet generally lower after a long retest interval (ranging from .56 to .77). Practice effects were only observed after a short retest interval (overall group mean gains up to 11 points), whereas no significant change in performance was found after a long retest interval. Furthermore, practice effect-adjusted SRB change norms were calculated for all WMS-IV-NL index scores. Overall, this study shows that the test-retest reliability of the WMS-IV-NL varied across indexes. Practice effects were observed after a short retest interval, but no evidence was found for practice effects after a long retest interval from one to two years. Finally, the SRB change norms were provided for the WMS-IV-NL.

  2. Sources, transport, and trends for selected trace metals and nutrients in the Coeur d'Alene and Spokane River Basins, Idaho, 1990-2013

    Science.gov (United States)

    Clark, Gregory M.; Mebane, Christopher A.

    2014-01-01

    Data collected at 18 streamflow-gaging and water-quality sampling sites in the Coeur d’Alene and Spokane River Basins of northern Idaho were used to estimate mean streamflow‑weighted concentrations and annual loads of total and dissolved cadmium, lead, and zinc, and total phosphorus (TP) and nitrogen (TN) for water years (WYs) 2009–13. Chronic Ambient Water Quality Criteria (AWQC) and AWQC ratios also were calculated to evaluate Idaho aquatic life criteria for chronic exposure to cadmium and zinc in streams. At four sites with a longer period of record, a Seasonal Kendall trend test was used to assess historical trends in the concentrations of total cadmium, lead, and zinc, and chronic AWQC ratios for cadmium and zinc during WYs 1990–2013.

  3. Update on the 22q11.2 deletion syndrome and its relevance to schizophrenia.

    Science.gov (United States)

    Van, Lily; Boot, Erik; Bassett, Anne S

    2017-05-01

    Schizophrenia occurs in ∼25% of individuals with 22q11.2 deletion syndrome (22q11.2DS), the strongest known molecular genetic risk factor for schizophrenia. This review highlights recent literature in 22q11.2DS as it pertains to psychosis and schizophrenia. Advances in noninvasive prenatal testing allow for early detection of 22q11.2DS in utero, whereas premature birth has been shown to be a significant risk factor for development of psychotic illness in 22q11.2DS. Impairments in various domains of cognitive and social functioning, as well as neuroanatomical alterations, are comparable with those in other high-risk groups and may serve as early signs of psychosis in 22q11.2DS. Novel research on the pathogenesis of schizophrenia in 22q11.2DS using cellular and mouse models indicates changes in expression of genes within the 22q11.2 deletion region and elsewhere in the genome, implicating molecular pathways involved in schizophrenia and associated neurocognitive deficits. Increased risks of obesity and of Parkinson's disease in 22q11.2DS warrant consideration in antipsychotic management. Progress in characterizing and predicting psychotic illness in 22q11.2DS supports this identifiable subpopulation as a molecular model with important implications for understanding the pathogenesis of schizophrenia in the general population and for development of potential novel therapies.

  4. Mosaic 22q11.2 microdeletion syndrome: diagnosis and clinical manifestations of two cases

    Directory of Open Access Journals (Sweden)

    Kabra Madhulika

    2008-08-01

    Full Text Available Abstract Chromosome 22q11.2 microdeletion syndrome is due to microdeletion of 22q11.2 region of chromosome 22. It is a common microdeletion syndrome however mosaic cases are very rare and reported only few previous occasions. In this report we describe two unrelated male children with clinical features consistent with 22q11.2 microdeletion syndrome characterized by cardiac defect, facial dysmorphism and developmental deficiency. One of the cases also had trigonocephaly. Interphase & metaphase FISH with 22q11.2 probe demonstrated mosaicism for hemizygous deletion of 22q11.2 region. Mosaicism is also observed in buccal cells as well as urine cells. Parents were without any deletion. These two cases represent rare cases of mosaic 22q11.2 microdeletion syndrome.

  5. Mosaic 22q11.2 microdeletion syndrome: diagnosis and clinical manifestations of two cases.

    Science.gov (United States)

    Halder, Ashutosh; Jain, Manish; Kabra, Madhulika; Gupta, Neerja

    2008-08-10

    Chromosome 22q11.2 microdeletion syndrome is due to microdeletion of 22q11.2 region of chromosome 22. It is a common microdeletion syndrome however mosaic cases are very rare and reported only few previous occasions. In this report we describe two unrelated male children with clinical features consistent with 22q11.2 microdeletion syndrome characterized by cardiac defect, facial dysmorphism and developmental deficiency. One of the cases also had trigonocephaly. Interphase & metaphase FISH with 22q11.2 probe demonstrated mosaicism for hemizygous deletion of 22q11.2 region. Mosaicism is also observed in buccal cells as well as urine cells. Parents were without any deletion. These two cases represent rare cases of mosaic 22q11.2 microdeletion syndrome.

  6. Hypocalcemia due to 22q11.2 deletion syndrome diagnosed in adulthood

    Directory of Open Access Journals (Sweden)

    Maria Cabrer

    2018-01-01

    Full Text Available Chromosome 22q11.2 deletion syndrome (22q11.2DS is a genetic syndrome that may present with hypocalcemia due to primary hypoparathyroidism (PH at any age. We report a new diagnosis of 22q11.2DS in a 57-year-old man who presented with symptomatic hypocalcemia. It is important to consider genetic causes of hypocalcemia due to PH regardless of age.

  7. Nasal dimple as part of the 22q11.2 deletion syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Gripp, K.W.; Reed, L.A. [Children`s Hospital of Philadelphia, PA (United States); Emanuel, B.S. [Children`s Hospital of Philadelphia, PA (United States)]|[Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1997-03-31

    The phenotype of the 22q11.2 microdeletion syndrome is quite variable. We describe 2 patients with a 22q11.2 deletion and a dimpled nasal tip, which, we suggest can be the extreme of the broad or bulbous nose commonly found in the 22q11.2 deletion syndrome, and should not be confused with the more severe nasal abnormalities seen in frontonasal dysplasia. 11 refs., 2 figs.

  8. Mosaic 22q11.2 microdeletion syndrome: diagnosis and clinical manifestations of two cases

    OpenAIRE

    Kabra Madhulika; Jain Manish; Halder Ashutosh; Gupta Neerja

    2008-01-01

    Abstract Chromosome 22q11.2 microdeletion syndrome is due to microdeletion of 22q11.2 region of chromosome 22. It is a common microdeletion syndrome however mosaic cases are very rare and reported only few previous occasions. In this report we describe two unrelated male children with clinical features consistent with 22q11.2 microdeletion syndrome characterized by cardiac defect, facial dysmorphism and developmental deficiency. One of the cases also had trigonocephaly. Interphase & metaphase...

  9. Familial 22q11.2 deletion syndrome with autosomal dominant inheritance

    Directory of Open Access Journals (Sweden)

    Bahar Gokturk

    2016-06-01

    Full Text Available 22q11.2 deletion syndrome is the most frequent microdeletion syndrome in humans and caused by hemizygote deletion on only one chromosome. Most of probands have a de novo deletion of 22q11.2, but 8-20% have inherited the 22q11.2 deletion from a parent (autosomal dominant mutation. Genotype-phenotype correlation is weak in this patient group. We aimed to present three members in the same family due to an autosomal dominant inheritance with 22q11.2 deletion and different clinical findings. [Cukurova Med J 2016; 41(2.000: 379-385

  10. Polymorphism analysis of IL17RA gene to the IL17RA concentration and chronicity differences in nefritis lupus NL patients

    Directory of Open Access Journals (Sweden)

    Mahrus Ismail

    2014-12-01

    Full Text Available Nefritis lupus (NL is autoimmune disease and one of serious complication from Systemic Eritematosus Lupus (LES. Clinical manifestation of NL was variated, there are hematuria microscopic asymptomatic until renal failure. In addition of clinical manifestation, the NL disorder degree also measured from histopathological grade. Although, the mechanism that mixed up with pathogenesis of NL was known, however the cytokine also play a role to the disease process. The cytokine that assumpted have a role to the inflammation is IL-17RA, the increase production of IL-17RA influenced to the in-flammation and NL chronicity degree. The aim of this study to analyzed the relationship between polymorphism of IL-17RA gene, blood IL-17RA con-centration with the NL disorder degree. These studies were used cross sectional with control case design. The sample were used 40 patients consist NL pa-tients and Lupus patient without nephritis as a control. The polymorphisms of IL-17RA gene were investigated by using PCR method and gene sequence analysis. The alterations of allele frequency of IL-17RA gene were analyzed by bioinformatics method. The bloods IL-17RA concentration were in-vestigated by ELISA method. The NL chronicity degrees were investigated by NL histopathological grade. The hypothesis were proofed by data normality test and homogeneity test, Chi-square and Odds ratio, Spearman correlation by using SPSS 17.0 for windows. The result of showed that there are sig-nificantly different between IL-17RA gene mutant genotype frequency of NL patient (NL with the control patient with value OR 8.48. There are sig-nificantly different between G allele of IL-17RA gene of NL patient (case with the control patient with the value OR 4.17. There are no significantly di-fferent between IL-17RA concentrations of NL patient (case with the different chronicity value. There are positive correlation with the OR value 4.17 bet-ween IL-17RA concentrations with the chronicity value

  11. Efficient non-sterilized fermentation of biomass-derived xylose to lactic acid by a thermotolerant Bacillus coagulans NL01.

    Science.gov (United States)

    Ouyang, Jia; Cai, Cong; Chen, Hai; Jiang, Ting; Zheng, Zhaojuan

    2012-12-01

    Xylose is the major pentose and the second most abundant sugar in lignocellulosic feedstock. Its efficient utilization is regarded as a technical barrier to the commercial production of bulk chemicals from lignocellulosic biomass. This work aimed at evaluating the lactic acid production from the biomass-derived xylose using non-sterilized fermentation by Bacillus coagulans NL01. A maximum lactic acid concentration of about 75 g/L was achieved from xylose of 100 g/L after 72 h batch fermentation. Acetic acid and levulinic acid were identified as important inhibitors in xylose fermentation, which markedly reduced lactic acid productivity at 15 and 1.0 g/L, respectively. But low concentrations of formic acid (coagulans NL01, the same preference for glucose, xylose, and arabinose was observed and18.2 g/L lactic acid was obtained after 48 h fermentation. These results proved that B. coagulans NL01 was potentially well-suited for producing lactic acid from underutilized xylose-rich prehydrolysates.

  12. Practical guidelines for managing adults with 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Fung, Wai Lun Alan; Butcher, Nancy J.; Costain, Gregory; Andrade, Danielle M.; Boot, Erik; Chow, Eva W. C.; Chung, Brian; Cytrynbaum, Cheryl; Faghfoury, Hanna; Fishman, Leona; García-Miñaúr, Sixto; George, Susan; Lang, Anthony E.; Repetto, Gabriela; Shugar, Andrea; Silversides, Candice; Swillen, Ann; van Amelsvoort, Therese; McDonald-McGinn, Donna M.; Bassett, Anne S.

    2015-01-01

    22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric

  13. Risk of Psychiatric Disorders Among Individuals With the 22q11.2 Deletion or Duplication

    DEFF Research Database (Denmark)

    Hoeffding, Louise K; Trabjerg, Betina B; Olsen, Line

    2017-01-01

    .64-14.69) and childhood autism (IRR, 8.94; 95%CI, 3.21-19.23). Conclusions and relevance: Individuals with the 22q11.2 deletion or duplication have a significantly increased risk of developing psychiatric disorders. Survival analysis of persons carrying either the 22q11.2 deletion or duplication provides estimates...

  14. Cardiac Defects and Results of Cardiac Surgery in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Carotti, Adriano; Digilio, Maria Cristina; Piacentini, Gerardo; Saffirio, Claudia; Di Donato, Roberto M.; Marino, Bruno

    2008-01-01

    Specific types and subtypes of cardiac defects have been described in children with 22q11.2 deletion syndrome as well as in other genetic syndromes. The conotruncal heart defects occurring in patients with 22q11.2 deletion syndrome include tetralogy of Fallot, pulmonary atresia with ventricular septal defect, truncus arteriosus, interrupted aortic…

  15. Autism Spectrum Disorder, Developmental and Psychiatric Features in 16p11.2 Duplication

    Science.gov (United States)

    Green Snyder, LeeAnne; D'Angelo, Debra; Chen, Qixuan; Bernier, Raphael; Goin-Kochel, Robin P.; Wallace, Arianne Stevens; Gerdts, Jennifer; Kanne, Stephen; Berry, Leandra; Blaskey, Lisa; Kuschner, Emily; Roberts, Timothy; Sherr, Elliot; Martin, Christa L.; Ledbetter, David H.; Spiro, John E.; Chung, Wendy K.; Hanson, Ellen

    2016-01-01

    The 16p11.2 duplication (BP4-BP5) is associated with Autism Spectrum Disorder (ASD), although significant heterogeneity exists. Quantitative ASD, behavioral and neuropsychological measures and DSM-IV diagnoses in child and adult carriers were compared with familial non-carrier controls, and to published results from deletion carriers. The 16p11.2

  16. Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements

    NARCIS (Netherlands)

    Demaerel, Wolfram; Hestand, Matthew S.; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A.; McDonald-Mcginn, Donna M.; Zackai, Elaine; Emanuel, Beverly S.; Morrow, Bernice E.; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R.; Antshel, Kevin M.; Arango, Celso; Armando, Marco; Bassett, Anne S.; Bearden, Carrie E.; Boot, Erik; Bravo-Sanchez, Marta; Breetvelt, Elemi; Busa, Tiffany; Butcher, Nancy J.; Campbell, Linda E.; Carmel, Miri; Chow, Eva W C; Crowley, T. Blaine; Cubells, Joseph; Cutler, David; Demaerel, Wolfram; Digilio, Maria Cristina; Duijff, Sasja; Eliez, Stephan; Emanuel, Beverly S.; Epstein, Michael P.; Evers, Rens; Fernandez Garcia-Moya, Luis; Fiksinski, Ania; Fraguas, David; Fremont, Wanda; Fritsch, Rosemarie; Garcia-Minaur, Sixto; Golden, Aaron; Gothelf, Doron; Guo, Tingwei; Gur, Ruben C.; Gur, Raquel E.; Heine-Suner, Damian; Hestand, Matthew; Hooper, Stephen R.; Kates, Wendy R.; Kushan, Leila; Laorden-Nieto, Alejandra; Maeder, Johanna; Marino, Bruno; Marshall, Christian R.; McCabe, Kathryn; McDonald-Mcginn, Donna M.; Michaelovosky, Elena; Morrow, Bernice E.; Moss, Edward; Mulle, Jennifer; Murphy, Declan; Murphy, Kieran C.; Murphy, Clodagh M.; Niarchou, Maria; Ornstein, Claudia; Owen, Michael J; Philip, Nicole; Repetto, Gabriela M.; Schneider, Maude; Shashi, Vandana; Simon, Tony J.; Swillen, Ann; Tassone, Flora; Unolt, Marta; Van Amelsvoort, Therese; van den Bree, Marianne B M; Van Duin, Esther; Vergaelen, Elfi; Vermeesch, Joris R.; Vicari, Stefano; Vingerhoets, Claudia; Vorstman, Jacob; Warren, Steve; Weinberger, Ronnie; Weisman, Omri; Weizman, Abraham; Zackai, Elaine; Zhang, Zhengdong; Zwick, Michael

    2017-01-01

    Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have

  17. 37 CFR 11.2 - Director of the Office of Enrollment and Discipline.

    Science.gov (United States)

    2010-07-01

    ... Enrollment and Discipline. 11.2 Section 11.2 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND... Discipline. (a) Appointment. The USPTO Director shall appoint a Director of the Office of Enrollment and Discipline (OED Director). In the event of a vacancy in the office of the OED Director, the USPTO Director...

  18. Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Butcher, Nancy J.; Kiehl, Tim-Rasmus; Hazrati, Lili-Naz; Chow, Eva W. C.; Rogaeva, Ekaterina; Lang, Anthony E.; Bassett, Anne S.

    2015-01-01

    IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical α-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological

  19. Movement Disorders and Other Motor Abnormalities in Adults With 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Boot, Erik; Butcher, Nancy J; van Amelsvoort, Thérèse AMJ; Lang, Anthony E; Marras, Connie; Pondal, Margarita; Andrade, Danielle M; Fung, Wai Lun Alan; Bassett, Anne S

    2015-01-01

    Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In addition to an increased susceptibility to neuropsychiatric disorders, seizures, and early-onset Parkinson disease, the underlying brain dysfunction associated with 22q11.2DS may give rise to an increased vulnerability to multiple movement abnormalities, including those influenced by medications. Movement abnormalities may also be secondary to treatable endocrine diseases and congenital musculoskeletal abnormalities. We propose that movement abnormalities may be common in adults with 22q11.2DS and discuss the implications and challenges important to clinical practice. PMID:25684639

  20. Congenital diaphragmatic hernia in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Unolt, Marta; DiCairano, Lauren; Schlechtweg, Kathryn; Barry, Jessica; Howell, Lori; Kasperski, Stefanie; Nance, Michael; Adzick, N Scott; Zackai, Elaine H; McDonald-McGinn, Donna M

    2017-01-01

    We report the important association of congenital diaphragmatic hernia (CDH) and 22q11.2 deletion syndrome (22q11.2DS). The prevalence of CDH in our cohort of patients with 22q11.2DS is 0.8% (10/1246), which is greater than in the general population (0.025%). This observation suggests that 22q11.2DS should be considered when a child or fetus presents with CDH, in particular when other clinical findings associated with the 22q11.2DS are present, such as congenital cardiac defects. Furthermore, this finding may lead to the identification of an additional locus for diaphragmatic hernia in the general population. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Wilms tumor in a patient with 22q11.2 microdeletion.

    Science.gov (United States)

    Finch, Paul T; Pivnick, Eniko K; Furman, Wayne; Odom, Christine C

    2011-05-01

    22q11.2 deletion syndrome is the most common microdeletion syndrome. Wilms tumor is one of the most common solid tumors in childhood yet 22q11.2 deletion and Wilms tumor only once have been reported in the same patient. Here we describe a young patient with subtle clinical findings suggestive of 22q11.2 at the time of diagnosis who subsequently developed Wilms tumor. We assert the importance of a low threshold for screening for 22q11.2 deletion and the associated phenotypes and maintaining vigilance in screening for common primary malignancies in patients with known 22q11.2 deletion. Copyright © 2011 Wiley-Liss, Inc.

  2. A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium

    Directory of Open Access Journals (Sweden)

    Berkhout Ben

    2005-02-01

    Full Text Available Abstract Background Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43 and 229E (HCoV-229E, SARS associated coronavirus (SARS-CoV and the recently identified human coronavirus NL63 (HCoV-NL63. In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. Methods Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. Results Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. Conclusions Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating.

  3. Social Impairments in Chromosome 22q11.2 Deletion Syndrome (22q11.2DS): Autism Spectrum Disorder or a Different Endophenotype?

    Science.gov (United States)

    Angkustsiri, Kathleen; Goodlin-Jones, Beth; Deprey, Lesley; Brahmbhatt, Khyati; Harris, Susan; Simon, Tony J.

    2014-01-01

    High prevalence of autism spectrum disorders (ASD) has been reported in 22q11.2DS, although this has been based solely on parent report measures. This study describes the presence of ASD using a procedure more similar to that used in clinical practice by incorporating history (Social Communication Questionnaire) AND a standardized observation…

  4. Measuring illness beliefs in patients with lower extremity injuries: reliability and validity of the Dutch version of the Somatic Pre-Occupation and Coping questionnaire (SPOC-NL).

    Science.gov (United States)

    Reininga, Inge H F; Brouwer, Sandra; Dijkstra, Anita; Busse, Jason W; Ebrahim, Shanil; Wendt, Klaus W; El Moumni, Mostafa

    2015-02-01

    Positive coping strategies, illness perceptions and recovery expectations are associated with better clinical outcomes and earlier return to work after injuries. The Somatic Pre-Occupation and Coping (SPOC) questionnaire captures illness beliefs and coping towards recovery of physical function and return to work after surgical treatment of tibial shaft fractures. The aim of this study was to translate and culturally adapt the SPOC into Dutch (SPOC-NL) and evaluate its reliability and validity in patients with lower extremity injuries. The SPOC-NL contains four subscales: Somatic complaints, Coping, Energy, and Optimism. Patients treated for lower extremity injuries (N=106) completed the SPOC-NL, Short Form-36 and Short Musculoskeletal Function Assessment (SMFA-NL) questionnaire, and reported their current work status and self-perceived work ability. To assess test-retest reliability, 56 patients completed the SPOC-NL for a second time two weeks after the first administration of the SPOC-NL. We calculated Cronbach's Alpha, intraclass correlation coefficients (ICCs) and G coefficients to measure internal consistency and overall reliability, and used the Bland and Altman method to assess bias between test and retest SPOC-NL scores. To determine construct validity, we explored 16 a priori hypotheses regarding correlations between SPOC-NL scores and subscale scores and SF-36, SMFA-NL, work status and work ability. Internal consistency was good to excellent, with Cronbach's Alpha values ranging between 0.79 and 0.94 and G coefficients ranging between 0.77 and 0.95. Test-retest reliability was also good, since high ICCs (0.72-0.91) and G coefficients (0.82-0.94) were found. Construct validity of the SPOC-NL was good, as 75% of the predefined hypotheses were confirmed. Compared to participants who were on sick leave or receiving disability benefits, participants with a paid job had significantly higher scores on the total score and the subscales Somatic complaints and

  5. Examining the Overlap between Autism Spectrum Disorder and 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Ousley, Opal; Evans, A Nichole; Fernandez-Carriba, Samuel; Smearman, Erica L; Rockers, Kimberly; Morrier, Michael J; Evans, David W; Coleman, Karlene; Cubells, Joseph

    2017-05-18

    22q11.2 deletion syndrome (22q11.2DS) is a genomic disorder reported to associate with autism spectrum disorders (ASDs) in 15-50% of cases; however, others suggest that individuals with 22q11.2DS present psychiatric or behavioral features associated with ASDs, but do not meet full criteria for ASD diagnoses. Such wide variability in findings may arise in part due to methodological differences across studies. Our study sought to determine whether individuals with 22q11.2DS meet strict ASD diagnostic criteria using research-based guidelines from the Collaborative Programs of Excellence in Autism (CPEA), which required a gathering of information from three sources: the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observational Schedule (ADOS), and a clinician's best-estimate diagnosis. Our study examined a cohort of children, adolescents, and young adults ( n = 56) with 22q11.2DS, who were ascertained irrespective of parents' behavioral or developmental concerns, and found that 17.9% ( n = 10) of the participants met CPEA criteria for an ASD diagnosis, and that a majority showed some level of social-communication impairment or the presence of repetitive behaviors. We conclude that strictly defined ASDs occur in a substantial proportion of individuals with 22q11.2DS, and recommend that all individuals with 22q11.2DS be screened for ASDs during early childhood.

  6. Prevalence of 22q11.2 microdeletion syndrome in Iranian patients with cleft palate.

    Science.gov (United States)

    Nouri, Narges; Memarzadeh, Mehrdad; Salehi, Mansoor; Nouri, Nayereh; Meamar, Rokhsareh; Behnam, Mahdiyeh; Derakhshandeh, Fatemeh; Kashkoolinejad, Tahereh; Abdali, Hossein

    2016-01-01

    22q11.2 microdeletion syndrome is the most common multiple genetic disorder associated with learning disabilities, developmental delays, immune deficiency, hypocalcemia, and cleft palate. Finding some valid criteria for screening of 22q11.2 deletion syndromes in infants would be very helpful in early diagnosis and treatment. Since 69% of individuals with 22q11.2 deletion have a palatal abnormality, we studied the prevalence of 22q11.2 deletion syndrome in 378 Iranian patients during a 5-year period, including 291 patients affected with cleft palate only without cleft lip (CPO) and 87 patients affected with velopharyngeal incompetence (VPI) and/or submucous cleft palate (SMCP). DNA copy number was analyzed with multiplex ligation-dependent probe amplification (MLPA) technique. In our study, 15/378 (3.97%) patients with palatal anomalies showed 22q11.2 deletion. Interestingly, this prevalence between syndromic patients was 15/104 (14.42%). It seems that SMCP or VPI, in addition to one or more another features of 22q11.2 deletions, especially developmental delay, may be good criteria for molecular investigation of 22q11.2 region.

  7. Examining the Overlap between Autism Spectrum Disorder and 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Opal Ousley

    2017-05-01

    Full Text Available 22q11.2 deletion syndrome (22q11.2DS is a genomic disorder reported to associate with autism spectrum disorders (ASDs in 15–50% of cases; however, others suggest that individuals with 22q11.2DS present psychiatric or behavioral features associated with ASDs, but do not meet full criteria for ASD diagnoses. Such wide variability in findings may arise in part due to methodological differences across studies. Our study sought to determine whether individuals with 22q11.2DS meet strict ASD diagnostic criteria using research-based guidelines from the Collaborative Programs of Excellence in Autism (CPEA, which required a gathering of information from three sources: the Autism Diagnostic Interview-Revised (ADI-R, the Autism Diagnostic Observational Schedule (ADOS, and a clinician’s best-estimate diagnosis. Our study examined a cohort of children, adolescents, and young adults (n = 56 with 22q11.2DS, who were ascertained irrespective of parents’ behavioral or developmental concerns, and found that 17.9% (n = 10 of the participants met CPEA criteria for an ASD diagnosis, and that a majority showed some level of social-communication impairment or the presence of repetitive behaviors. We conclude that strictly defined ASDs occur in a substantial proportion of individuals with 22q11.2DS, and recommend that all individuals with 22q11.2DS be screened for ASDs during early childhood.

  8. Parkinson's disease associated with 22q11.2 deletion: Clinical characteristics and response to treatment.

    Science.gov (United States)

    Dufournet, B; Nguyen, K; Charles, P; Grabli, D; Jacquette, A; Borg, M; Danaila, T; Mutez, E; Drapier, S; Colin, O; Eusebio, A; Philip, N; Azulay, J P

    2017-06-01

    While it is known that 22q11.2 microdeletions (22q11.2-del) increase the risk of Parkinson's disease (PD), the characteristics of PD associated with 22q11.2-del have not been specifically explored. This report aimed to assess the clinical characteristics and treatment responses of PD patients with 22q11.2-del, and to describe any features that might lead neurologists to investigate the comorbidity. Nine PD patients (eight men, one woman) with 22q11.2-del were followed at seven centers of the French PD Expert Network (Ns-Park). PD diagnosis was made before 22q11.2-del diagnosis in seven cases; their main characteristics were early onset (32-48 years) and good initial levodopa sensitivity, but with a course characterized by severe and early-onset levodopa-induced motor complications and psychiatric manifestations. Three patients received deep brain stimulation (DBS) that was effective. Searching for 22q11.2-del in PD patients presenting with suggestive features is relevant as the clinical presentation is similar to idiopathic PD, but with other associated characteristics, including a severe evolution. Results with DBS are similar to those reported for idiopathic PD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Psychopathology and cognition in children with 22q11.2 deletion syndrome

    Science.gov (United States)

    Niarchou, Maria; Zammit, Stanley; van Goozen, Stephanie H. M.; Thapar, Anita; Tierling, Hayley M.; Owen, Michael J.; van den Bree, Marianne B. M.

    2014-01-01

    Background Children with 22q11.2 deletion syndrome (22q11.2DS) have been reported to have high rates of cognitive and psychiatric problems. Aims To establish the nature and prevalence of psychiatric disorder and neurocognitive impairment in children with 22q11.2DS and test whether risk of psychopathology is mediated by the children’s intellectual impairment. Method Neurocognition and psychopathology were assessed in 80 children with 22q11.2DS (mean age 10.2 years, s.d. = 2.1) and 39 sibling controls (mean age 10.9 years, s.d. = 2.0). Results More than half (54%) of children with 22q11.2DS met diagnostic criteria for one or more DSM-IV-TR psychiatric disorder. These children had lower IQ (mean 76.8, s.d. = 13.0) than controls (mean 108.6, s.d. = 15.2) (Ppsychopathology was not mediated by intellectual impairment. Conclusions 22q11.2DS is not related to a specific psychiatric phenotype in children. Moreover, the deletion has largely independent effects on IQ and risk of psychopathology, indicating that psychopathology in 22q11.2DS is not a non-specific consequence of generalised cognitive impairment. PMID:24115343

  10. High prevalence of fatigue in adults with a 22q11.2 deletion syndrome.

    Science.gov (United States)

    Vergaelen, Elfi; Claes, Stephan; Kempke, Stefan; Swillen, Ann

    2017-04-01

    The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with high phenotypic variability, including somatic disorders like congenital heart disease and psychiatric disorders such as schizophrenia, anxiety disorders, and mood disorders. Clinical observations suggest that many patients with 22q11.2DS suffer from severe fatigue. However, to the best of our knowledge, no previous study has investigated the potential association between 22q11.2DS and fatigue. Twenty-nine patients (mean age 26.8, 18-38 y) with 22q11.2DS completed the multidimensional fatigue inventory (MFI) measuring severity of fatigue. The results of the study group were compared with published population norms. In addition, cross-sectional associations between fatigue, depression (Beck Depression Inventory-BDI), and a quality of life questionnaire (WHO) in patients with 22q11.2 DS were examined. Subscales and total MFI scores were significantly higher in adults with 22q11.2DS. Approximately 80% of the study group had a total MFI score above the mean of the norms. A significant correlation between depressive symptoms and fatigue was found. Fatigue was also significantly associated with quality of life scores, specifically the general score, psychological health, and environment. This is the first report of high levels of fatigue in adults with the 22q11.2DS. Fatigue is a frequent complaint in this age group and should get the necessary attention given its association with quality of life and depression severity. Taking into account the multisystem nature of the 22q11.2DS, we recommend a systematic clinical examination to exclude underlying somatic or psychiatric causes of fatigue. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. The dimensional structure of psychopathology in 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Niarchou, Maria; Moore, Tyler M; Tang, Sunny X; Calkins, Monica E; McDonald-McGuinn, Donna M; Zackai, Elaine H; Emanuel, Beverly S; Gur, Ruben C; Gur, Raquel E

    2017-09-01

    22q11.2 Deletion Syndrome (22q11.2DS) is one of the strongest known genetic risk factors for developing schizophrenia. Individuals with 22q11.2DS have high rates of neurodevelopmental disorders in childhood, while in adulthood ∼25% develop schizophrenia. Similar to the general population, high rates of comorbidity are common in 22q11.2DS. Employing a dimensional approach where psychopathology is examined at the symptom-level as complementary to diagnostic categories in a population at such high genetic risk for schizophrenia can help gain a better understanding of how psychopathology is structured as well as its genetic underpinnings. This is the first study to examine the dimensional structure of a wide spectrum of psychopathology in the context of a homogeneous genetic etiology like 22q11.2DS. We evaluated 331 individuals with 22q11.2DS, mean age (SD) = 16.9(8.7); 51% males, who underwent prospective comprehensive phenotyping. We sought to replicate previous findings by examining a bi-factor model that derives a general factor of psychopathology in addition to more specific dimensions of psychopathology (i.e., internalizing, externalizing and thought disorder). Psychopathology in 22q11.2DS was divided into one 'general psychopathology' factor and four specific dimensions (i.e., 'anxiety', 'mood', 'ADHD' and 'psychosis'). The 'psychosis' symptoms loaded strongly on the 'general psychopathology' factor. The similarity of the symptom structure of psychopathology between 22q11.2DS and community and clinical populations without the deletion indicate that 22q11.2DS can provide a model to explore alternative approaches to our current nosology. Our findings add to a growing literature indicating the need to reorganize current diagnostic classification systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Practical guidelines for managing adults with 22q11.2 deletion syndrome

    OpenAIRE

    Fung, Wai Lun Alan; Butcher, Nancy J.; Costain, Gregory; Andrade, Danielle M.; Boot, Erik; Chow, Eva W.C.; Chung, Brian; Cytrynbaum, Cheryl; Faghfoury, Hanna; Fishman, Leona; García-Miñaúr, Sixto; George, Susan; Lang, Anthony E.; Repetto, Gabriela; Shugar, Andrea

    2015-01-01

    22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existin...

  13. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah L. Pachtman

    2016-01-01

    Full Text Available Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia.

  14. [Diagnosis of 22q11.2 deletion syndrome in the context of newly developed psychosis].

    Science.gov (United States)

    Kaltenboeck, Alexander; Friedrich, Fabian; Hinterbuchinger, Barbara; Litvan, Zsuzsa; Mossaheb, Nilufar

    2016-12-01

    22q11.2 deletion syndrome (clinically also known as velocardiofacial or DiGeorge syndrome) is the most common human microdeletion syndrome and can be associated with a multitude of clinical features. In this article we report the case of a 22-year-old patient from Austria who was diagnosed with previously unknown 22q11.2 deletion syndrome in the context of newly developed psychosis. Using this case as an example, we then discuss the implications of 22q11.2 deletion syndrome for clinical psychiatric practice.

  15. A rare association of interrupted aortic arch type C and microdeletion 22q11.2.

    Science.gov (United States)

    Cuturilo, Goran; Drakulic, Danijela; Stevanovic, Milena; Jovanovic, Ida; Djukic, Milan; Miletic-Grkovic, Slobodanka; Atanaskovic-Markovic, Marina

    2008-10-01

    Microdeletion 22q11.2 is associated with a variety of findings, and the most common are cardiac defects. It is very frequently associated with interrupted aortic arch (IAA) type B and very rarely with type A and type C. Here we report the first case of IAA type C associated with 22q11.2 deletion in Serbia and, to the best of our knowledge, the fourth case described worldwide so far. By this report we would like to point out that all patients with IAA type C who have additional features specific for 22q11.2 microdeletion syndrome should be screened for the presence of this deletion.

  16. Practical guidelines for managing adults with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Fung, Wai Lun Alan; Butcher, Nancy J; Costain, Gregory; Andrade, Danielle M; Boot, Erik; Chow, Eva W C; Chung, Brian; Cytrynbaum, Cheryl; Faghfoury, Hanna; Fishman, Leona; García-Miñaúr, Sixto; George, Susan; Lang, Anthony E; Repetto, Gabriela; Shugar, Andrea; Silversides, Candice; Swillen, Ann; van Amelsvoort, Therese; McDonald-McGinn, Donna M; Bassett, Anne S

    2015-08-01

    22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities.Genet Med 17 8, 599-609.

  17. Mouse Models of 22q11.2-Associated Autism Spectrum Disorder

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    Hiroi, Noboru; Hiramoto, Takeshi; Harper, Kathryn M.; Suzuki, Go; Boku, Shuken

    2013-01-01

    Copy number variation (CNV) of human chromosome 22q11.2 is associated with an elevated rate of autism spectrum disorder (ASD) and represents one of syndromic ASDs with rare genetic variants. However, the precise genetic basis of this association remains unclear due to its relatively large hemizygous and duplication region, including more than 30 genes. Previous studies using genetic mouse models suggested that although not all 22q11.2 genes contribute to ASD symptomatology, more than one 22q11.2 genes have distinct phenotypic targets for ASD symptoms. Our data show that deficiency of the two 22q11.2 genesTbx1 and Sept5 causes distinct phenotypic sets of ASD symptoms. PMID:25089229

  18. Practical guidelines for managing adults with 22q11.2 deletion syndrome

    Science.gov (United States)

    Fung, Wai Lun Alan; Butcher, Nancy J.; Costain, Gregory; Andrade, Danielle M.; Boot, Erik; Chow, Eva W.C.; Chung, Brian; Cytrynbaum, Cheryl; Faghfoury, Hanna; Fishman, Leona; García-Miñaúr, Sixto; George, Susan; Lang, Anthony E.; Repetto, Gabriela; Shugar, Andrea; Silversides, Candice; Swillen, Ann; van Amelsvoort, Therese; McDonald-McGinn, Donna M.; Bassett, Anne S.

    2015-01-01

    22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities. PMID:25569435

  19. The importance of understanding cognitive trajectories: the case of 22q11.2 deletion syndrome

    Science.gov (United States)

    Swillen, Ann

    2017-01-01

    Purpose of review 22q11.2 deletion syndrome (DS) (velocardiofacial syndrome or DiGeorge syndrome) is the most common known contiguous gene deletion syndrome and is associated with neurodevelopmental problems and diverse neuropsychiatric disorders across the life span. In this review, we discuss the wide variability in intelligence, the developmental phenotypic transitions regarding cognitive development (intelligence) from preschool to adolescence, and the importance of understanding these cognitive trajectories in 22q11.2 DS for care/management and research. Recent findings Longitudinal data on the cognitive development of children and adolescents with 22q11.2 DS reveal divergent cognitive trajectories. A decline in verbal IQ precedes the onset of psychosis in 22q11.2 DS. Summary Understanding these cognitive trajectories is important since it can guide clinicians to develop adequate support, tailored remediation, and psychiatric care and individualized follow-up. PMID:26779858

  20. FAMILIAL CASE OF CHROMOSOME 22q11.2 DELETION SYNDROME

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    I. A. Tuzankina

    2017-01-01

    Full Text Available The work represents a family which includes two siblings with chromosome 22q11.2 deletion syndrome. Their mother carries the same chromosome anomaly, but with apparently normal phenotype. Hence, this interesting case of 22q11.2 deletion syndrome exists in 2 generations of the same family. The aim of this study was analysis of phenotypic manifestations in the family members with 22q11.2 deletion syndrome. Clinical examination of the patients, their life story and pedigree and, along with routine clinical and biochemical analysis, and immune state testing, along with ultrasound imaging of thymus and thyroid glands, heart and abdominal cavity. We made conclusions that the phenotypic features associated with chromosome 22q11.2 deletion may be different for distinct family members. Further studies are required to determine length of deleted segment and the genes affected, as well as to establish the genotype-phenotype interactions and disease prognosis.

  1. [22q11.2DS Syndrome as a Genetic Subtype of Schizophrenia].

    Science.gov (United States)

    Huertas-Rodríguez, Cindy Katherin; Payán-Gómez, César; Forero-Castro, Ruth Maribel

    2015-01-01

    The 22q11.2 deletion syndrome (22q11.2DS) is associated with the microdeletion of this chromosomal region, and represents the second most common genetic syndrome after Down's syndrome. In patients with schizophrenia, 22q11.2DS has a prevalence of 2%, and in selected groups can be increased to between 32-53%. To describe the generalities of 22q11.2DS syndrome as a genetic subtype of schizophrenia, its clinical characteristics, molecular genetic aspects, and frequency in different populations. A review was performed from 1967 to 2013 in scientific databases, compiling articles about 22q11.2DS syndrome and its association with schizophrenia. The 22q11.2 DS syndrome has a variable phenotype associated with other genetic syndromes, birth defects in many tissues and organs, and a high rate of psychiatric disorders, particularly schizophrenia. Likewise, it has been identified in clinical populations with schizophrenia selected by the presence of common syndromic characteristics. FISH, qPCR and MLPA techniques, and recently, aCGH and NGS technologies, are being used to diagnose this microdeletion. It is important in clinical practice to remember that people suffering the 22q11.2DS have a high genetic risk for developing schizophrenia, and it is considered that the simultaneous presence of this disease and 22q11.2DS represents a genetic subtype of schizophrenia. There are clear phenotypic criteria, molecular and cytogenetic methods to diagnose this group of patients, and to optimize a multidisciplinary approach in their monitoring. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  2. Prevalence and Nature of Hearing Loss in 22q11.2 Deletion Syndrome

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    Van Eynde, Charlotte; Swillen, Ann; Lambeens, Elien; Verhaert, Nicolas; Desloovere, Christian; Luts, Heleen; Vander Poorten, Vincent; Devriendt, Koenraad; Hens, Greet

    2016-01-01

    Purpose: The purpose of this study was to clarify the prevalence, type, severity, and age-dependency of hearing loss in 22q11.2 deletion syndrome. Method: Extensive audiological measurements were conducted in 40 persons with proven 22q11.2 deletion (aged 6-36 years). Besides air and bone conduction thresholds in the frequency range between 0.125…

  3. Variety of prenatally diagnosed congenital heart disease in 22q11.2 deletion syndrome

    Science.gov (United States)

    Lee, Mi-Young; Baek, Ju Won; Cho, Jae-Hyun; Shim, Jae-Yoon; Lee, Pil-Ryang; Kim, Ahm

    2014-01-01

    Objective To analyze the spectrum of prenatally diagnosed congenital heart disease in a Korean population with 22q11.2 deletion syndrome, and to provide guidelines for screening 22q11.2 deletion prenatally. Methods This retrospective study evaluated 1,137 consecutive fetuses that had prenatal genetic testing for 22q11.2 deletion because of suspected congenital heart disease between September 2002 and December 2012, at Asan Medical Center, Seoul, Korea. Results Main cardiovascular diseases in the 53 fetuses with confirmed 22q11.2 deletions were tetralogy of Fallot (n = 24, 45%), interrupted aortic arch (n = 10, 19%), ventricular septal defect (n = 5, 9%), double outlet right ventricle (n = 4, 8%), and coarctation of the aorta (n = 4, 8%). Other cardiac defects were rarely associated with 22q11.2 deletion. One fetus had persistent truncus arteriosus, one had aortic stenosis, and one had hypoplastic right heart syndrome. Two fetuses had normal intracardiac anatomy with an isolated right aortic arch, and one had an isolated bilateral superior vena cava. Conclusion A variety of congenital heart diseases were seen during the prenatal period. Conotruncal cardiac defects except transposition of great arteries were strongly associated with 22q11.2 deletion. When such anomalies are diagnosed by fetal echocardiography, genetic testing for 22q11.2 deletion should be offered. Even if less frequent deletion-related cardiac defects are detected, other related anomalies, such as thymic hypoplasia or aplasia, should be evaluated to rule out a 22q11.2 deletion. PMID:24596813

  4. Altered auditory processing and effective connectivity in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Larsen, Kit Melissa; Mørup, Morten; Birknow, Michelle Rosgaard; Fischer, Elvira; Hulme, Oliver; Vangkilde, Anders; Schmock, Henriette; Baaré, William Frans Christiaan; Didriksen, Michael; Olsen, Line; Werge, Thomas; Siebner, Hartwig R; Garrido, Marta I

    2018-01-30

    22q11.2 deletion syndrome (22q11.2DS) is one of the most common copy number variants and confers a markedly increased risk for schizophrenia. As such, 22q11.2DS is a homogeneous genetic liability model which enables studies to delineate functional abnormalities that may precede disease onset. Mismatch negativity (MMN), a brain marker of change detection, is reduced in people with schizophrenia compared to healthy controls. Using dynamic causal modelling (DCM), previous studies showed that top-down effective connectivity linking the frontal and temporal cortex is reduced in schizophrenia relative to healthy controls in MMN tasks. In the search for early risk-markers for schizophrenia we investigated the neural basis of change detection in a group with 22q11.2DS. We recorded high-density EEG from 19 young non-psychotic 22q11.2 deletion carriers, as well as from 27 healthy non-carriers with comparable age distribution and sex ratio, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Despite finding no significant reduction in the MMN responses, whole-scalp spatiotemporal analysis of responses to the tones revealed a greater fronto-temporal N1 component in the 22q11.2 deletion carriers. DCM showed reduced intrinsic connection within right primary auditory cortex as well as in the top-down, connection from the right inferior frontal gyrus to right superior temporal gyrus for 22q11.2 deletion carriers although not surviving correction for multiple comparison. We discuss these findings in terms of reduced adaptation and a general increased sensitivity to tones in 22q11.2DS. Copyright © 2018. Published by Elsevier B.V.

  5. Visual processing deficits in 22q11.2 Deletion Syndrome.

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    Biria, Marjan; Tomescu, Miralena I; Custo, Anna; Cantonas, Lucia M; Song, Kun-Wei; Schneider, Maude; Murray, Micah M; Eliez, Stephan; Michel, Christoph M; Rihs, Tonia A

    2018-01-01

    Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task. Significant differences between groups emerged at early and late stages of visual processing. In 22q11.2DS, we first observed reduced amplitudes over occipital channels and reduced source activations within dorsal and ventral visual stream areas during the P1 (100-125 ms) and within ventral visual cortex during the N1 (150-170 ms) visual evoked components. During a later window implicated in visual completion (240-285 ms), we observed an increase in global amplitudes in 22q11.2DS. The increased surface amplitudes for illusory contours at this window were inversely correlated with positive subscales of prodromal symptoms in 22q11.2DS. The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia.

  6. Incidence of the 22q11.2 deletion in a large cohort of miscarriage samples.

    Science.gov (United States)

    Maisenbacher, Melissa K; Merrion, Katrina; Pettersen, Barbara; Young, Michael; Paik, Kiyoung; Iyengar, Sushma; Kareht, Stephanie; Sigurjonsson, Styrmir; Demko, Zachary P; Martin, Kimberly A

    2017-01-01

    The 22q11.2 deletion syndrome is the most common microdeletion syndrome in livebirths, but data regarding its incidence in other populations is limited and also include ascertainment bias. This study was designed to determine the incidence of the 22q11.2 deletion in miscarriage samples sent for clinical molecular cytogenetic testing. Twenty-six thousand one hundred one fresh product of conception (POC) samples were sent to a CLIA- certified, CAP-accredited laboratory from April 2010--May 2016 for molecular cytogenetic miscarriage testing using a single-nucleotide polymorphism (SNP)-based microarray platform. A retrospective review determined the incidence of the 22q11.2 deletion in this sample set. Fetal results were obtained in 22,451 (86%) cases, of which, 15 (0.07%) had a microdeletion in the 22q11.2 region (incidence, 1/1497). Of those, 12 (80%) cases were found in samples that were normal at the resolution of traditional karyotyping (i.e., had no chromosome abnormalities above 10 Mb in size) and three (20%) cases had additional findings (Trisomy 15, Trisomy 16, XXY). Ten (67%) cases with a 22q11.2 deletion had the common ~3 Mb deletion; the remaining 5 cases had deletions ranging in size from 0.65 to 1.5 Mb. A majority (12/15) of cases had a deletion on the maternally inherited chromosome. No significant relationship between maternal age and presence of a fetal 22q11.2 deletion was observed. The observed incidence of 1/1497 for the 22q11.2 deletion in miscarriage samples is higher than the reported general population prevalence (1/4000-1/6000). Further research is needed to determine whether the 22q11.2 deletion is a causal factor for miscarriage.

  7. The Development of Cognitive Control in Children with Chromosome 22q11.2 Deletion Syndrome

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    Heather M Shapiro

    2014-06-01

    Full Text Available Chromosome 22q11.2 Deletion Syndrome (22q11.2DS is caused by the most common human microdeletion, and it is associated with cognitive impairments across many domains. While impairments in cognitive control have been described in children with 22q11.2DS, the nature and development of these impairments are not clear. Children with 22q11.2DS and typically developing children (TD were tested on four well-validated tasks aimed at measuring specific foundational components of cognitive control: response inhibition, cognitive flexibility, and working memory. Molecular assays were also conducted in order to examine genotype of catechol-O-methyltransferase (COMT, a gene located within the deleted region in 22q11.2DS and hypothesized to play a role in cognitive control. Mixed model regression analyses were used to examine group differences, as well as age-related effects on cognitive control component processes in a cross-sectional analysis. Regression models with COMT genotype were also conducted in order to examine potential effects of the different variants of the gene. Response inhibition, cognitive flexibility, and working memory were impaired in children with 22q11.2DS relative to TD children, even after accounting for global intellectual functioning (as measured by full-scale IQ. When compared with TD individuals, children with 22q11.2DS demonstrated atypical age-related patterns of response inhibition and cognitive flexibility. Both groups demonstrated typical age-related associations with working memory. The results of this cross-sectional analysis suggest a specific aberration in the development of systems mediating response inhibition in a sub-set of children with 22q11.2DS. It will be important to follow up with longitudinal analyses to directly examine these developmental trajectories, and correlate neurocognitive variables with clinical and adaptive outcome measures.

  8. Obesity in adults with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Voll, Sarah L; Boot, Erik; Butcher, Nancy J; Cooper, Samantha; Heung, Tracy; Chow, Eva W C; Silversides, Candice K; Bassett, Anne S

    2017-02-01

    To characterize the prevalence of and contributing factors to adult obesity in the most common recurrent copy-number variation (CNV), 22q11.2 deletion, given that other rare CNVs are known to have obesity phenotypes. In 207 adults with 22q11.2 deletion syndrome (22q11.2DS), we used available height and weight measurements to calculate body mass index (BMI) and recorded associated factors that could play a role in obesity. We used the maximum BMI per subject and logistic regression to test a model predicting obesity class. The prevalence of obesity (BMI ≥30) in 22q11.2DS (n = 90, 43.5%; at median age of 26.7 years) was significantly greater than for Canadian norms (odds ratio (OR) 2.30, 95% confidence interval (CI) = 1.74-3.02, P obesity level. Ten (4.8%) individuals were diagnosed with type 2 diabetes at a median age of 39.5 years; the prevalence was higher in those with obesity (P adult obesity is related to the 22q11.2 deletion. The findings expand the potential genetic causes of obesity and have important implications for management of 22q11.2DS.Genet Med 19 2, 204-208.

  9. PWS/AS MS-MLPA Confirms Maternal Origin of 15q11.2 Microduplication

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    Angelika J. Dawson

    2015-01-01

    Full Text Available The proximal region of the long arm of chromosome 15q11.2-q13 is associated with various neurodevelopmental disorders, including Prader-Willi (PWS and Angelman (AS syndromes, autism, and other developmental abnormalities resulting from deletions and duplications. In addition, this region encompasses imprinted genes that cause PWS or AS, depending on the parent-of-origin. This imprinting allows for diagnosis of PWS or AS based on methylation status using methylation sensitive (MS multiplex ligation dependent probe amplification (MLPA. Maternally derived microduplications at 15q11.2-q13 have been associated with autism and other neuropsychiatric disorders. Multiple methods have been used to determine the parent-of-origin for 15q11.2-q13 microdeletions and microduplications. In the present study, a four-year-old nondysmorphic female patient with developmental delay was found to have a de novo ~5 Mb duplication within 15q11.2 by oligonucleotide genomic array. In order to determine the significance of this microduplication to the clinical phenotype, the parent-of-origin needed to be identified. The PWS/AS MS-MLPA assay is generally used to distinguish between deletion and uniparental disomy (UPD of 15q11.2-q13, resulting in either PWS or AS. However, our study shows that PWS/AS MS-MLPA can also efficiently distinguish the parental origin of duplications of 15q11.2-q13.

  10. Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.

    Science.gov (United States)

    Demaerel, Wolfram; Hestand, Matthew S; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Morrow, Bernice E; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R

    2017-10-05

    Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders. Copyright © 2017. Published by Elsevier Inc.

  11. Distal 22q11.2 Microduplication: Case Report and Review of the Literature.

    Science.gov (United States)

    Pinchefsky, Elana; Laneuville, Laurence; Srour, Myriam

    2017-01-01

    Distal chromosome 22q11.2 microduplications are associated with a wide range of phenotypes and unclear pathogenicity. The authors report on a 3-year-old girl with global developmental delay harboring a de novo 1.24 Mb distal chromosome 22q11.2 microduplication and a paternally inherited 0.25 Mb chromosome 4p14 microduplication. The authors review clinical features of 30 reported cases of distal 22q11.2 duplications. Common features include developmental delay (93%), neuropsychiatric features (26%), and nonspecific facial dysmorphisms (74%). In 70% of cases, the distal 22q11.2 duplications were inherited, and the majority of the carrier parents were phenotypically normal. Furthermore, 30% of probands carried an additional copy number variant. Review of the phenotype in individuals carrying microduplications involving similar low copy repeats (LCR) failed to establish any clear genotype-phenotype correlations. Distal 22q11.2 duplications represent a major challenge for genetic counseling and prediction of clinical consequences. Our report suggests a pathogenic role of distal 22q11.2 duplications and supports a "multiple hit" hypothesis underlying its variable expressivity and phenotypic severity.

  12. Failure to detect the 22q11.2 duplication syndrome rearrangement among patients with schizophrenia

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    Vallès Vicenç

    2008-02-01

    Full Text Available Abstract Chromosome aberrations have long been studied in an effort to identify susceptibility genes for schizophrenia. Chromosome 22q11.2 microdeletion is associated with DiGeorge and Velocardiofacial syndromes (DG/VCF and provides the most convincing evidence of an association between molecular cytogenetic abnormality and schizophrenia. In addition, this region is one of the best replicated linkage findings for schizophrenia. Recently, the reciprocal microduplication on 22q11.2 has been reported as a new syndrome. Preliminary data indicates that individuals with these duplications also suffer from neuropsychiatric disorders. In this study we have investigated the appropriateness of testing schizophrenia patients for the 22q11.2 microduplication. We used multiplex ligation-dependent probe amplification (MLPA to measure copy number changes on the 22q11.2 region in a sample of 190 patients with schizophrenia. Our results corroborate the prevalence of the 22q11.2 microdeletion in patients with schizophrenia and clinical features of DG/VCFS and do not suggest an association between 22q11.2 microduplication and schizophrenia.

  13. [Prenatal diagnosis of 22q11.2 microdeletion by multiplex ligation-dependent probe amplification].

    Science.gov (United States)

    Luo, Chun-yu; Ma, Ding-yuan; Zhang, Jing-jing; Hu, Ping; Cao, Li; Ji, Xiu-qing; Zhou, Jing; Liu, An; Wu, Yun; Cheng, Jian; Lin, Ying; Xu, Zheng-feng

    2013-11-01

    To explore the clinical value of multiplex ligation-dependent probe amplification (MLPA) technique performed in prenatal diagnosis of chromosome 22q11.2 microdeletion. MLPA was performed to detect chromosome 22q11.2 mircodeletion in 62 fetuses with congenital heart defects by fetal echocardiography and a normal karyotype by standard G-banding analysis.For a 22q11.2 mircodeletion fetus, his parents were detected to know if it is inherited or de novo. The microdeletion was confirmed by array-based comparative genomic hybridization (arrayCGH). MLPA revealed five 22q11.2 mircodeletions in the 62 fetuses, and the positive detection rate was 8% (5/62). Among these, 4 cases carried the 3M typically deletion which all are de novo, and 1 case carried the 1.5M non-typically deletion which was inherited from his father.arrayCGH confirmed the 22q11.2 microdeletions and delineated the precise location and size of microdeletions. MLPA has clinical value in prenatal diagnosis of 22q11.2 mircodeletion, which could provide important genetic information for genetic consulting, pregnancy management and intervention after birth.

  14. Neuroanatomical phenotypes in a mouse model of the 22q11.2 microdeletion.

    Science.gov (United States)

    Ellegood, J; Markx, S; Lerch, J P; Steadman, P E; Genç, C; Provenzano, F; Kushner, S A; Henkelman, R M; Karayiorgou, M; Gogos, J A

    2014-01-01

    Recurrent deletions at the 22q11.2 locus have been established as a strong genetic risk factor for the development of schizophrenia and cognitive dysfunction. Individuals with 22q11.2 deletions have a range of well-defined volumetric abnormalities in a number of critical brain structures. A mouse model of the 22q11.2 deletion (Df(16)A(+/-)) has previously been utilized to characterize disease-associated abnormalities on synaptic, cellular, neurocircuitry, and behavioral levels. We performed a high-resolution MRI analysis of mutant mice compared with wild-type littermates. Our analysis revealed a striking similarity in the specific volumetric changes of Df(16)A(+/-) mice compared with human 22q11.2 deletion carriers, including in cortico-cerebellar, cortico-striatal and cortico-limbic circuits. In addition, higher resolution magnetic resonance imaging compared with neuroimaging in human subjects allowed the detection of previously unknown subtle local differences. The cerebellar findings in Df(16)A(+/-) mice are particularly instructive as they are localized to specific areas within both the deep cerebellar nuclei and the cerebellar cortex. Our study indicates that the Df(16)A(+/-)mouse model recapitulates most of the hallmark neuroanatomical changes observed in 22q11.2 deletion carriers. Our findings will help guide the design and interpretation of additional complementary studies and thereby advance our understanding of the abnormal brain development underlying the emergence of 22q11.2 deletion-associated psychiatric and cognitive symptoms.

  15. Disrupted fornix integrity in children with chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Deng, Yi; Goodrich-Hunsaker, Naomi J; Cabaral, Margarita; Amaral, David G; Buonocore, Michael H; Harvey, Danielle; Kalish, Kristopher; Carmichael, Owen T; Schumann, Cynthia M; Lee, Aaron; Dougherty, Robert F; Perry, Lee M; Wandell, Brian A; Simon, Tony J

    2015-04-30

    The fornix is the primary subcortical output fiber system of the hippocampal formation. In children with 22q11.2 deletion syndrome (22q11.2DS), hippocampal volume reduction has been commonly reported, but few studies as yet have evaluated the integrity of the fornix. Therefore, we investigated the fornix of 45 school-aged children with 22q11.2DS and 38 matched typically developing (TD) children. Probabilistic diffusion tensor imaging (DTI) tractography was used to reconstruct the body of the fornix in each child׳s brain native space. Compared with children, significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) was observed bilaterally in the body of the fornix in children with 22q11.2DS. Irregularities were especially prominent in the posterior aspect of the fornix where it emerges from the hippocampus. Smaller volumes of the hippocampal formations were also found in the 22q11.2DS group. The reduced hippocampal volumes were correlated with lower fornix FA and higher fornix RD in the right hemisphere. Our findings provide neuroanatomical evidence of disrupted hippocampal connectivity in children with 22q11.2DS, which may help to further understand the biological basis of spatial impairments, affective regulation, and other factors related to the ultra-high risk for schizophrenia in this population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Validity and reliability of the Dutch version of the Copenhagen Hip And Groin Outcome Score (HAGOS-NL in patients with hip pathology.

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    Hilde Giezen

    Full Text Available The Copenhagen Hip And Groin Outcome Score (HAGOS was developed to assess disease-specific consequences in young to middle-aged, physically active hip and/or groin patients. The study aimed to determine validity and reliability of the Dutch version of the HAGOS (HAGOS-NL for middle-aged patients with hip complaints.To assess validity, 117 participants completed five questionnaires: HAGOS-NL, international Hip Outcome Tool (iHOT-12NL, Hip disability and Osteoarthritis Outcome Score (HOOS, RAND-36 Health Survey and Tegner activity scale. Structural validity was determined by conducting confirmatory factor analysis. Construct validity was analyzed by formulating predefined hypotheses regarding relationships between the HAGOS-NL and subscales of the iHOT-12NL, HOOS, RAND-36 and Tegner activity scale. The HAGOS-NL was filled out again by 67 patients to explore test-retest reliability. Reliability was assessed in terms of Cronbach's alpha, Intraclass Correlation Coefficient (ICC, Standard Error of Measurement (SEM and Minimal Detectable Change (MDC. The Bland and Altman method was used to explore absolute agreement.Factor analysis confirmed that the HAGOS-NL consists of six subscales. All hypotheses were confirmed, indicating good construct validity. Internal consistency was good, with Cronbach's alpha values ranging from 0.89 to 0.98. Test-retest reliability was considered good, with ICC values of 0.80 and higher. The SEM ranged from 6.6 to 12.3, and MDC at individual level from 18.3 to 34.1 and at group level from 2.3 to 4.4. Bland and Altman analyses showed no bias.The HAGOS-NL is a reliable and valid instrument for measuring pain, physical functioning and quality of life in middle-aged patients with hip complaints.

  17. Cardiac sympathetic activity in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Verschure, Derk O; Boot, Erik; van Amelsvoort, Thérèse A; Booij, Jan; van Eck-Smit, Berthe L F; Somsen, G Aernout; Verberne, Hein J

    2016-06-01

    22q11.2 deletion syndrome (22q11.2DS) affects catechol-O-methyl-transferase (COMT), which involves the degradation of norepinephrine (NE). Clinically, adults with 22q11.2DS are at increased risk for sudden unexpected death. Although the causes are likely multifactorial, increased cardiac sympathetic activity with subsequent fatal arrhythmia, due to increased levels of NE, should be considered as a possible mechanism predisposing to this premature death. The purpose of this study was to determine whether cardiac sympathetic activity is increased in 22q11.2DS, both at baseline and following an acute NE depletion with alpha-methyl-para-tyrosine (AMPT). Five adults with 22q11.2DS and five age- and sex-matched healthy controls underwent 2 sessions with either AMPT or placebo administration before (123)I-mIBG scintigraphy. Heart-to-mediastinum ratios (H/M) were determined from the images 15min (early) and 4h (late) after administration of (123)I-mIBG and the washout (WO) was calculated as an indicator of adrenergic drive. At baseline there were no significant differences in both early and late H/M between 22q11.2DS and controls. However, there was a significant difference in WO between 22q11.2DS and controls (-4.92±2.8 and -10.44±7.2, respectively; p=0.027), but a "negative WO" does not support an increased sympathetic drive. In addition there was a trend towards a higher late H/M after AMPT administration compared to baseline which was more pronounced in 22q11.2DS. This study for the first time suggests normal cardiac sympathetic activity in adults with 22q11.2DS assessed by (123)I-mIBG scintigraphy. Although there is a small difference in adrenergic drive compared to healthy subjects, this most likely does not explain the increased unexpected death rate in the 22q11.2 DS population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Attention Deficit Hyperactivity Disorder Symptoms and Psychosis in 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Niarchou, Maria; Calkins, Monica E; Moore, Tyler M; Tang, Sunny X; McDonald-McGinn, Donna M; Zackai, Elaine H; Emanuel, Beverly S; Gur, Ruben C; Gur, Raquel E

    2017-10-10

    22q11.2 Deletion Syndrome (22q11.2DS) is associated with increased risk for schizophrenia in adulthood while Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent diagnosis in childhood. Inattention symptoms are pronounced in 22q11.2DS and given that attentional impairment is a core feature of schizophrenia, inattention symptoms may reflect underlying ADHD, psychosis, or both. We investigate whether inattention is associated with psychosis in 22q11.2DS and in other groups at risk for psychosis but without the deletion (ND) (idiopathic clinical risk and first degree family members of individuals with schizophrenia). One hundred thirty-seven individuals with 22q11.2DS (mean age: 14.0), 84 ND individuals with subthreshold psychosis (mean age: 16.9) and 31 ND individuals with family history of psychosis (mean age: 17.0) were included in the study. Psychopathology was assessed using research diagnostic assessments. ADHD total symptoms were associated with overall levels of subthreshold psychosis symptoms in 22q11.2DS (β = .8, P = .04). Inattention symptoms were specifically associated with positive (β = .5, P = .004), negative (β = .5, P = .03), and disorganized (β = .5, P hyperactivity-impulsivity symptoms were associated with disorganized symptoms (β = .5, P = .01). The prevalence of ADHD inattention symptoms was higher in 22q11.2DS with subthreshold psychosis compared to ND individuals with subthreshold psychosis (P < .001), even when adjusting for cognitive impairment and overall psychopathology. The pattern was similar when comparing individuals with 22q11.2DS and ND individuals with family history of psychosis. This is the first study to examine the associations between ADHD symptoms and psychosis in 22q11.2DS. Our findings support a potentially important role of ADHD inattention symptoms in psychosis in 22q11.2DS. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights

  19. 22q11.2 deletion syndrome: attitudes towards disclosing the risk of psychiatric illness.

    Science.gov (United States)

    Martin, Nicole; Mikhaelian, Marina; Cytrynbaum, Cheryl; Shuman, Cheryl; Chitayat, David A; Weksberg, Rosanna; Bassett, Anne S

    2012-12-01

    22q11.2 Deletion Syndrome (22q11.2DS) is a common microdeletion syndrome with multisystem features. There is a strong association with psychiatric disorders. One in every four to five patients develop schizophrenia. Despite studies showing that early diagnosis and treatment are likely to lead to improved outcome, genetic counselors may be reluctant to discuss the risk of psychiatric illness. The aim of this research was to explore parental attitudes and genetic counselors' perspectives and practice regarding disclosure of the clinical manifestations of 22q11.2DS, particularly the risk of psychiatric illness. We delivered a questionnaire to genetic counselors via established list-serves, 54 of which were completed. We also conducted interviews with four parents of adults with 22q11.2DS and schizophrenia. The majority of counselors and parents felt that the increased risk to develop a psychiatric illness is important to disclose. However, in the initial counseling session when the diagnosis was made in infancy genetic counselors were significantly less likely to discuss the risk of psychiatric disorders compared to other later onset features such as hypothyroidism (41 % vs. 83 %, p = 0.001). When the diagnosis of 22q11.2DS was made in infancy, counselors' responses in regard to timing of disclosure about psychiatric illnesses were fairly evenly divided between infancy, childhood and adolescence. In contrast, for other major features of 22q11.2DS, disclosure would predominantly be in infancy. The respondents reported that the discussion of psychiatric issues with parents was challenging due to the stigma associated with mental illness. Some also noted limited knowledge about psychiatric illness and treatment. These results suggest that genetic counselors could benefit from further education regarding psychiatric illness in 22q11.2DS and best strategies for discussing this important subject with parents and patients.

  20. 22q11.2 deletion syndrome lowers seizure threshold in adult patients without epilepsy.

    Science.gov (United States)

    Wither, Robert G; Borlot, Felippe; MacDonald, Alex; Butcher, Nancy J; Chow, Eva W C; Bassett, Anne S; Andrade, Danielle M

    2017-06-01

    Previous studies examining seizures in patients with 22q11.2 deletion syndrome (22q11.2DS) have focused primarily on children and adolescents. In this study we investigated the prevalence and characteristics of seizures and epilepsy in an adult 22q11.2DS population. The medical records of 202 adult patients with 22q11.2DS were retrospectively reviewed for documentation of seizures, electroencephalography (EEG) reports, and magnetic resonance imaging (MRI) findings. Epilepsy status was assigned in accordance with 2010 International League Against Epilepsy Classification. Of 202 patients, 32 (15.8%) had a documented history of seizure. Of these 32, 23 (71.8%) had acute symptomatic seizures, usually associated with hypocalcemia and/or antipsychotic or antidepressant use. Nine patients (9/32, 28%; 9/202, 4%) met diagnostic criteria for epilepsy. Two patients had genetic generalized epilepsy; two patients had focal seizures of unknown etiology; two had epilepsy due to malformations of cortical development; in two the epilepsy was due to acquired structural changes; and in one patient the epilepsy could not be further classified. Similarly to children, the prevalence of epilepsy and acute symptomatic seizures in adults with 22q11.2DS is higher than in the general population. Hypocalcemia continues to be a risk factor for adults, but differently from kids, the main cause of seizures in adults with 22q11.2DS is exposure to antipsychotics and antidepressants. Further prospective studies are warranted to investigate how 22q11.2 microdeletion leads to an overall decreased seizure threshold. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  1. The clinical learning environment and supervision instrument (CLES): validity and reliability of the Dutch version (CLES+NL).

    Science.gov (United States)

    De Witte, Nico; Labeau, Sonia; De Keyzer, Willem

    2011-05-01

    The clinical learning environment and supervision scale (CLES) is a valid and reliable tool that was developed to assess the quality of nursing students' clinical placements. To obtain a reliable and valid Dutch version of the CLES that is in line with the Flemish culture and educational context. Scale validation study on data provided by a cross-sectional survey. 190 wards in 31 institutions for healthcare in Flanders, Belgium. 768 student nurses enrolled in the 3 year bachelor programme at University College Ghent, Faculty of Healthcare Vesalius. Face and content validation was followed by data collection. Factor analysis was performed using varimax rotation. Subsequently, internal consistency reliability was tested on the total scale and its subdimensions using Cronbach's alpha. We gathered 768 questionnaires. Factor analysis revealed 5 subdimensions with an eigenvalue greater than 1, explaining 71.281% of the variance. The overall internal consistency and the consistency of the five subdimensions is high. Our data supports face, content and construct validity of the CLES+NL. The CLES+NL is a valid and reliable instrument that can be used to evaluate the quality of nursing wards as learning environments in Flanders. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

    Science.gov (United States)

    Lin, Amy; Ching, Christopher R K; Vajdi, Ariana; Sun, Daqiang; Jonas, Rachel K; Jalbrzikowski, Maria; Kushan-Wells, Leila; Pacheco Hansen, Laura; Krikorian, Emma; Gutman, Boris; Dokoru, Deepika; Helleman, Gerhard; Thompson, Paul M; Bearden, Carrie E

    2017-06-28

    Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development. SIGNIFICANCE STATEMENT Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly

  3. Opitz GBBB syndrome and the 22q11.2 deletion

    Energy Technology Data Exchange (ETDEWEB)

    Lacassie, Y.; Arriaza, M.I. [Louisiani State Univ. Medical Center and Children`s Hospital, New Orleans, LA (United States)

    1996-03-29

    Recently, McDonald-McGinn et al. reported the presence of a deletion 22q11.2 in a family with autosomal dominant inheritance and in a sporadic case with the Opitz GBBB syndrome. The presence of a vascular ring in these patients prompted them to look for this deletion, since this anomaly may be associated with the 22q11.2 deletion. They reviewed the Opitz GBBB syndrome and the 22q11.2 microdeletion syndrome, finding considerable overlap of manifestations. They proposed that, in some patients, the Opitz GBBB syndrome may be due to a 22q11.2 deletion. We recently examined a newborn boy referred because of MCA. The cardinal findings in this patient (hypertelorism, hypospadias with descended testicles, characteristic nose and truncus arteriosus type I) were suggestive of the Opitz GBBB syndrome and of the velocardiofacial syndrome. The chromosomes were apparently normal (46,XY), but the FISH study showed a 22q11.2 deletion. The patient developed hypocalcemia with very low level of PTH and heart failure requiring surgery. His immunological status was normal except that CD4 cells were mildly low and natural killer cells were increased in number. The family history was noncontributory, but the full evaluation of the family is pending. The mother at first glance presents apparent hypertelorism. 3 refs.

  4. Congenital respiratory tract disorders in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Verheij, Emmy; Speleman, Lucienne; Mink van der Molen, Aebele B; Thomeer, Henricus G X M

    2018-01-01

    Respiratory tract disorders have been reported in patients with 22q11.2 deletion syndrome, however infrequently. This study describes the respiratory tract disorders encountered in a cohort of 278 patients with 22q11.2 deletion syndrome. We conducted a retrospective, cross-sectional, study at a single tertiary referral center. We identified the patients with 22q11.2 deletion syndrome and with an upper and/or lower respiratory tract disorder at our otorhinolaryngologic department. The different disorders were described. Out of 278 patients referred to the otorhinolaryngologic department, we identified 14 patients with a laryngeal and/or tracheal disorder. Nine patients had more than one congenital disorder in this anatomical area. Disorders included a choanal stenosis (n = 1), laryngeal web (n = 5), laryngeal cleft (n = 2), subglottic stenosis (n = 3), pharyngo-, laryngo-, tracheo- and/or bronchomalacia (n = 11) and tracheal stenosis (n = 1). Different types of respiratory tract disorders can be present in patients with 22q11.2 deletion syndrome. Clinicians should be aware of this clinical association for timely and accurate diagnosis and treatment. In addition, the diagnosis 22q11.2 deletion syndrome should be considered in patients presenting with a congenital respiratory tract disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Neuropsychiatric aspects of 22q11.2 deletion syndrome: considerations in the prenatal setting

    Science.gov (United States)

    Bassett, Anne S.; Costain, Gregory; Marshall, Christian R.

    2016-01-01

    Most major neuropsychiatric outcomes of concern to families are not detectable by prenatal ultrasound. The introduction of genome-wide chromosomal microarray analysis to prenatal clinical diagnostic testing has increased the detection of pathogenic 22q11.2 deletions, which cause the most common genomic disorder. The recent addition of this and other microdeletions to non-invasive prenatal screening methods using cell-free fetal DNA has further propelled interest in outcomes. Conditions associated with 22q11.2 deletions include intellect ranging from intellectual disability to average, schizophrenia and other treatable psychiatric conditions, epilepsy, and early-onset Parkinson’s disease. However, there is currently no way to predict how severe the lifetime expression will be. Available evidence suggests no major role in these neuropsychiatric outcomes for the congenital cardiac or most other structural anomalies that may be detectable on ultrasound. This article provides an outline of the lifetime neuropsychiatric phenotype of 22q11.2 deletion syndrome that will be useful to clinicians involved in prenatal diagnosis and related genetic counselling. The focus is on information that will be most relevant to two common situations: detection of a 22q11.2 deletion in a fetus or newborn, and new diagnosis of 22q11.2 deletion syndrome in a parent without a previous molecular diagnosis. PMID:27718271

  6. Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype and deletion size.

    Science.gov (United States)

    Halder, Ashutosh; Jain, Manish; Chaudhary, Isha; Varma, Binuja

    2012-03-13

    We report on a pair of male monozygotic twins with 22q11.2 microdeletion, discordant phenotype and discordant deletion size. The second twin had findings suggestive of DiGeorge syndrome, while the first twin had milder anomalies without any cardiac malformation. The second twin had presented with intractable convulsion, cyanosis and cardiovascular failure in the fourth week of life and expired on the sixth week of life, whereas the first twin had some characteristic facial appearance with developmental delay but no other signs of the 22q11.2 microdeletion syndrome including cardiovascular malformation. The fluorescence in situ hybridization (FISH) analysis had shown a microdeletion on the chromosome 22q11.2 in both twins. The interphase FISH did not find any evidence for the mosaicism. The genomic DNA microarray analysis, using HumanCytoSNP-12 BeadChip (Illumina), was identical between the twins except different size of deletion of 22q11.2. The zygosity using HumanCytoSNP-12 BeadChip (Illumina) microarray analysis suggested monozygosity. This observation indicates that altered size of the deletion may be the underlying etiology for the discordance in phenotype in monozygotic twins. We think early post zygotic events (mitotic non-allelic homologous recombination) could have been played a role in the alteration of 22q11.2 deletion size and, thus phenotypic variability in the monozygotic twins.

  7. Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome.

    Science.gov (United States)

    Choi, Jin-Ho; Shin, Young-Lim; Kim, Gu-Hwan; Seo, Eul-Ju; Kim, Youngho; Park, In-Sook; Yoo, Han-Wook

    2005-01-01

    Endocrine abnormalities, including hypocalcemia, thyroid dysfunction, and short stature, are associated with chromosome 22q11.2 microdeletion syndrome. This study was undertaken to examine the frequencies and clinical features of endocrine abnormalities in patients with 22q11.2 microdeletion syndrome. We analyzed 61 patients with 22q11.2 microdeletion syndrome diagnosed based on the verification of microdeletion by fluorescent in situ hybridization (FISH) using a probe of the DiGeorge syndrome critical region (TUPLE1) at 22q11.2 and a control probe, ARSA at 22q13. Serum total calcium, phosphorus, and intact parathyroid hormone (PTH) levels were measured, thyroid function test was performed, and serum IGF-1 and IGFBP-3 levels were also estimated. Height and weight of patients were compared with individual chronological ages. Hypocalcemia was found in 20 patients (32.8%), and overt hypoparathyroidism in 8 (13.1%). Two patients (3.3%) showed autoimmune thyroid diseases, 1 each with Graves' disease and Hashimoto thyroiditis. Ten patients (16.4%) were below the third percentile in height, but the serum IGF-1 level was normal in 9 out of these 10 patients. Our findings show that patients with chromosome 22q11.2 microdeletion syndrome present with variable endocrine manifestations and variable clinical phenotypes. In addition to FISH analysis, careful endocrine evaluations are required in patients with this microdeletion syndrome, particularly for those with hypoparathyroidism or thyroid dysfunction. Copyright 2005 S. Karger AG, Basel.

  8. Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype and deletion size

    Directory of Open Access Journals (Sweden)

    Halder Ashutosh

    2012-03-01

    Full Text Available Abstract We report on a pair of male monozygotic twins with 22q11.2 microdeletion, discordant phenotype and discordant deletion size. The second twin had findings suggestive of DiGeorge syndrome, while the first twin had milder anomalies without any cardiac malformation. The second twin had presented with intractable convulsion, cyanosis and cardiovascular failure in the fourth week of life and expired on the sixth week of life, whereas the first twin had some characteristic facial appearance with developmental delay but no other signs of the 22q11.2 microdeletion syndrome including cardiovascular malformation. The fluorescence in situ hybridization (FISH analysis had shown a microdeletion on the chromosome 22q11.2 in both twins. The interphase FISH did not find any evidence for the mosaicism. The genomic DNA microarray analysis, using HumanCytoSNP-12 BeadChip (Illumina, was identical between the twins except different size of deletion of 22q11.2. The zygosity using HumanCytoSNP-12 BeadChip (Illumina microarray analysis suggested monozygosity. This observation indicates that altered size of the deletion may be the underlying etiology for the discordance in phenotype in monozygotic twins. We think early post zygotic events (mitotic non-allelic homologous recombination could have been played a role in the alteration of 22q11.2 deletion size and, thus phenotypic variability in the monozygotic twins.

  9. DiGeorge anomaly in the absence of chromosome 22q11.2 deletion.

    Science.gov (United States)

    Rope, Alan F; Cragun, Deborah L; Saal, Howard M; Hopkin, Robert J

    2009-10-01

    To test the hypothesis that the prevalence of deletion 22q11.2 among individuals who meet criteria for DiGeorge anomaly (DGA) is lower than the 90% commonly cited. Participants were identified through retrospective chart reviews on all patients who underwent testing for deletion 22q11.2 and all patients with a diagnosis of "DiGeorge" or any of the major criteria associated with DGA at a large pediatric hospital over a period of 6 years. DGA was confirmed in 64 individuals, based on the presence of at least 2 of the following features: (1) cellular immune deficiency and/or absence of part or all of the thymus; (2) hypocalcemia and/or parathyroid deficiency; (3) congenital heart disease. Of the 64 individuals with DGA, 29 (45%) did not have a chromosome 22q11.2 deletion. Among this deletion-negative subset, diabetic embryopathy and other chromosome abnormalities were the most commonly recognized underlying etiologies. These findings challenge a widely held belief that nearly 90% of DGA is due to chromosome 22q11.2 deletion. This study also calls attention to the heterogeneity of DGA, highlights similarities and differences between those with and without a chromosome 22q11.2 deletion, and attempts to resolve some confusing features of conditions associated with DGA.

  10. Reciprocal Deletion and Duplication of 17p11.2-11.2: Korean Patients with Smith-Magenis Syndrome and Potocki-Lupski Syndrome

    OpenAIRE

    Lee, Cha Gon; Park, Sang-Jin; Yun, Jun-No; Yim, Shin-Young; Sohn, Young Bae

    2012-01-01

    Deletion and duplication of the -3.7-Mb region in 17p11.2 result in two reciprocal syndrome, Smith-Magenis syndrome and Potocki-Lupski syndrome. Smith-Magenis syndrome is a well-known developmental disorder. Potocki-Lupski syndrome has recently been recognized as a microduplication syndrome that is a reciprocal disease of Smith-Magenis syndrome. In this paper, we report on the clinical and cytogenetic features of two Korean patients with Smith-Magenis syndrome and Potocki-Lupski syndrome. Pat...

  11. Diversity and Evolutionary Histories of Human Coronaviruses NL63 and 229E Associated with Acute Upper Respiratory Tract Symptoms in Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Al-Khannaq, Maryam Nabiel; Ng, Kim Tien; Oong, Xiang Yong; Pang, Yong Kek; Takebe, Yutaka; Chook, Jack Bee; Hanafi, Nik Sherina; Kamarulzaman, Adeeba; Tee, Kok Keng

    2016-05-04

    The human alphacoronaviruses HCoV-NL63 and HCoV-229E are commonly associated with upper respiratory tract infections (URTI). Information on their molecular epidemiology and evolutionary dynamics in the tropical region of southeast Asia however is limited. Here, we analyzed the phylogenetic, temporal distribution, population history, and clinical manifestations among patients infected with HCoV-NL63 and HCoV-229E. Nasopharyngeal swabs were collected from 2,060 consenting adults presented with acute URTI symptoms in Kuala Lumpur, Malaysia, between 2012 and 2013. The presence of HCoV-NL63 and HCoV-229E was detected using multiplex polymerase chain reaction (PCR). The spike glycoprotein, nucleocapsid, and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. A total of 68/2,060 (3.3%) subjects were positive for human alphacoronavirus; HCoV-NL63 and HCoV-229E were detected in 45 (2.2%) and 23 (1.1%) patients, respectively. A peak in the number of HCoV-NL63 infections was recorded between June and October 2012. Phylogenetic inference revealed that 62.8% of HCoV-NL63 infections belonged to genotype B, 37.2% was genotype C, while all HCoV-229E sequences were clustered within group 4. Molecular dating analysis indicated that the origin of HCoV-NL63 was dated to 1921, before it diverged into genotype A (1975), genotype B (1996), and genotype C (2003). The root of the HCoV-229E tree was dated to 1955, before it diverged into groups 1-4 between the 1970s and 1990s. The study described the seasonality, molecular diversity, and evolutionary dynamics of human alphacoronavirus infections in a tropical region. © The American Society of Tropical Medicine and Hygiene.

  12. Transposition of the great arteries - a phenotype associated with 16p11.2 duplications?

    Science.gov (United States)

    Karunanithi, Zarmiga; Vestergaard, Else Marie; Lauridsen, Mette H

    2017-12-26

    Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations, suggesting that they may be significant to the aetiology of the disease. This paper reports the identification of a 16p11.2 microduplication, a variation that has yet to be reported in association with transposition of the great arteries. The 16p11.2 microduplication is associated with autism spectrum disorder and developmental delay, but with highly variable phenotypic effects. Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population. Neonatal surgery is proposed as a risk factor, but as yet unidentified genetic abnormalities should also be taken into account. Thus, congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16p11.2. We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.

  13. Autism Spectrum Disorder, Developmental and Psychiatric Features in 16p11.2 Duplication.

    Science.gov (United States)

    Green Snyder, LeeAnne; D'Angelo, Debra; Chen, Qixuan; Bernier, Raphael; Goin-Kochel, Robin P; Wallace, Arianne Stevens; Gerdts, Jennifer; Kanne, Stephen; Berry, Leandra; Blaskey, Lisa; Kuschner, Emily; Roberts, Timothy; Sherr, Elliot; Martin, Christa L; Ledbetter, David H; Spiro, John E; Chung, Wendy K; Hanson, Ellen

    2016-08-01

    The 16p11.2 duplication (BP4-BP5) is associated with Autism Spectrum Disorder (ASD), although significant heterogeneity exists. Quantitative ASD, behavioral and neuropsychological measures and DSM-IV diagnoses in child and adult carriers were compared with familial non-carrier controls, and to published results from deletion carriers. The 16p11.2 duplication phenotype ranges widely from asymptomatic presentation to significant disability. The most common diagnoses were intellectual disability, motor delays and Attention Deficit Hyperactivity Disorder in children, and anxiety in adults. ASD occurred in nearly 20 % of child cases, but a majority of carriers did not show the unique social features of ASD. The 16p11.2 duplication phenotype is characterized by wider variability than the reciprocal deletion, likely reflecting contributions from additional risk factors.

  14. Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland

    OpenAIRE

    Wozniak, Anna; Wolnik-Brzozowska, Danuta; Wisniewska, Marzena; Glazar, Renata; Materna-Kiryluk, Anna; Moszura, Tomasz; Badura-Stronka, Magdalena; Skolozdrzy, Joanna; Krawczynski, Maciej R; Zeyland, Joanna; Bobkowski, Waldemar; Slomski, Ryszard; Latos-Bielenska, Anna; Siwinska, Aldona

    2010-01-01

    Abstract Background The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering...

  15. Reciprocal deletion and duplication of 17p11.2-11.2: Korean patients with Smith-Magenis syndrome and Potocki-Lupski syndrome.

    Science.gov (United States)

    Lee, Cha Gon; Park, Sang-Jin; Yun, Jun-No; Yim, Shin-Young; Sohn, Young Bae

    2012-12-01

    Deletion and duplication of the -3.7-Mb region in 17p11.2 result in two reciprocal syndrome, Smith-Magenis syndrome and Potocki-Lupski syndrome. Smith-Magenis syndrome is a well-known developmental disorder. Potocki-Lupski syndrome has recently been recognized as a microduplication syndrome that is a reciprocal disease of Smith-Magenis syndrome. In this paper, we report on the clinical and cytogenetic features of two Korean patients with Smith-Magenis syndrome and Potocki-Lupski syndrome. Patient 1 (Smith-Magenis syndrome) was a 2.9-yr-old boy who showed mild dysmorphic features, aggressive behavioral problems, and developmental delay. Patient 2 (Potocki-Lupski syndrome), a 17-yr-old boy, had only intellectual disabilities and language developmental delay. We used array comparative genomic hybridization (array CGH) and found a 2.6 Mb-sized deletion and a reciprocal 2.1 Mb-sized duplication involving the 17p11.2. These regions overlapped in a 2.1 Mb size containing 11 common genes, including RAI1 and SREBF.

  16. Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Levy-Shraga, Yael; Gothelf, Doron; Goichberg, Zohar; Katz, Uriel; Somech, Raz; Pinhas-Hamiel, Orit; Modan-Moses, Dalit

    2017-05-01

    22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features including endocrine abnormalities. We aimed to characterize growth patterns, hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS. Anthropometric and laboratory measurements were obtained from the charts of 48 individuals (males=28, 8.0±6.8 visits/participant) followed at a national 22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3±4.9 years and age at last evaluation 11.2±7.2 years. Median height-SDS was negative at all ages. Height-SDS at last visit was correlated to the midparental height-SDS (r=0.52 P=0.002). Yet, participants did not reach their target height, with a difference of 1.06±1.07 SD (P <0.0001). Height-SDS at last visit of participants with a heart defect was lower compared to participants with a normal heart (-1.5±1.4 vs. -0.6±0.8, P=0.036), with lower height-SDS in the subgroup of participants with severe heart defects (-2.1±1.6, P=0.009). Mean IGF1-SDS was low (-0.99±1.68) but was not correlated with height-SDS. Thirteen patients (27%) had hypoparathyroidism: 10 presented during infancy and 3 during adolescence. Five patients (10.4%, female=4) had thyroid abnormalities. In conclusions, individuals with 22q11.2 DS have a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Hypoparathyroidism is common and may present during the neonatal period as well as later in life. Thyroid abnormalities may present during childhood, adolescence, or adulthood. © 2017 Wiley Periodicals, Inc.

  17. Genotype-phenotype correlation in 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Michaelovsky Elena

    2012-12-01

    Full Text Available Abstract Background The 22q11.2 deletion syndrome (22q11.2DS is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion. Methods Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation. Results Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2% carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted. Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes. Conclusions MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms. Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.

  18. Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome.

    Science.gov (United States)

    Koczkowska, Magdalena; Wierzba, Jolanta; Śmigiel, Robert; Sąsiadek, Maria; Cabała, Magdalena; Ślężak, Ryszard; Iliszko, Mariola; Kardaś, Iwona; Limon, Janusz; Lipska-Ziętkiewicz, Beata S

    2017-02-01

    Chromosome 22q11.2 deletion syndrome, one of the most common human genomic syndromes, has highly heterogeneous clinical presentation. Patients usually harbor a 1.5 to 3 Mb hemizygous deletion at chromosome 22q11.2, resulting in pathognomic TBX1, CRKL and/or MAPK1 haploinsufficiency. However, there are some individuals with clinical features resembling the syndrome who are eventually diagnosed with genomic disorders affecting other chromosomal regions. The objective of this study was to evaluate the additive value of high-resolution array-CGH testing in the cohort of 41 patients with clinical features of 22q11.2 deletion syndrome and negative results of standard cytogenetic diagnostic testing (karyotype and FISH for 22q11.2 locus). Array-CGH analysis revealed no aberrations at chromosomes 22 or 10 allegedly related to the syndrome. Five (12.2 %) patients were found to have other genomic imbalances, namely 17q21.31 microdeletion syndrome (MIM#610443), 1p36 deletion syndrome (MIM#607872), NF1 microduplication syndrome (MIM#613675), chromosome 6pter-p24 deletion syndrome (MIM#612582) and a novel interstitial deletion at 3q26.31 of 0.65 Mb encompassing a dosage-dependent gene NAALADL2. Our study demonstrates that the implementation of array-CGH into the panel of classic diagnostic procedures adds significantly to their efficacy. It allows for detection of constitutional genomic imbalances in 12 % of subjects with negative result of karyotype and FISH targeted for 22q11.2 region. Moreover, if used as first-tier genetic test, the method would provide immediate diagnosis in ∼40 % phenotypic 22q11.2 deletion subjects.

  19. Clinical variability of chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Boyarchuk, Oksana; Volyanska, Liubov; Dmytrash, Liubov

    2017-01-01

    22q11.2 deletion syndrome (22q11.2 DS) is a disorder that has multiple symptoms and affects various organs and systems. Despite the great variability of clinical manifestations, common 22q11.2 DS includes congenital heart defect, immunodeficiency, characteristic facial features, palatal defects, developmental and/or learning disabilities, and hypocalcaemia. We present the cases of three patients with 22q11.2 DS that we have observed. Heart defects were revealed in all cases, and tetralogy of Fallot in one of them. Immune system disorders in these cases were highly variable and did not correlate with aplasia or hypoplasia of the thymus. Cleft palate was diagnosed only in one case. Characteristic facial features were presented in all cases but they were not significant and varied from subtle to mild. Developmental disability was presented by motor delays in two cases. Hypocalcaemia was revealed in one patient, and seizures were absent. Only one case completely fit CATCH-22 syndrome (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcaemia caused by22q11.2 deletion). The other cases had three out of the five main features, with some other, less significant signs also presented. In some cases, even just a few signs should be the reason for further examination to exclude 22q11.2 deletion syndrome. Currently, immunological disorders are not a significant determinant in the diagnosis of this syndrome, and timely correction of heart defects can reduce the number of recurrent respiratory infections. A multidisciplinary approach to the management of these patients and providing timely, complex medical care will prevent serious complications.

  20. Neuroanatomical Phenotypes in a Mouse Model of the 22q11.2 Microdeletion

    Science.gov (United States)

    Lerch, J.P.; Steadman, P.E.; Genç, C.; Provenzano, F; Kushner, S.A.; Henkelman, R.M.; Karayiorgou, M.; Gogos, J.A.

    2013-01-01

    Recurrent deletions at the 22q11.2 locus have been established as a strong genetic risk factor for the development of schizophrenia and cognitive dysfunction. Individuals with 22q11.2 deletions have a range of well-defined volumetric abnormalities in a number of critical brain structures. A mouse model of the 22q11.2 deletion (Df(16)A+/−) has previously been utilized to characterize disease-associated abnormalities on synaptic, cellular, neurocircuitry, and behavioral levels. We performed a high-resolution MRI analysis of mutant mice compared with wild-type (WT) littermates. Our analysis revealed a striking similarity in the specific volumetric changes of Df(16)A+/− mice compared with human 22q11.2 deletion carriers, including in cortico-cerebellar, cortico-striatal, and cortico-limbic circuits. In addition, higher resolution compared with neuroimaging in human subjects allowed detection of previously unknown subtle local differences. The cerebellar findings in Df(16)A+/− mice are particularly instructive as they are localized to specific areas within both the deep cerebellar nuclei and the cerebellar cortex. Our study indicates that the Df(16)A+/− mouse model recapitulates most of the hallmark neuroanatomical changes observed in 22q11.2 deletion carriers. Our findings will help guide the design and interpretation of additional complementary studies and thereby advance our understanding of the abnormal brain development underlying the emergence of 22q11.2 deletion-associated psychiatric and cognitive symptoms. PMID:23999526

  1. 22q11.2 deletion (DiGeorge syndrome: a mother’s open letter

    Directory of Open Access Journals (Sweden)

    Antonio Baldini

    2011-07-01

    Full Text Available Dear E.G., this is an open letter on 22q11.2 deletion syndrome (DiGeorge syndrome. You are the mother of a beautiful 3 year old child. And you are one of the most active members of Aidel22, the Italian Association of 22q deletion syndrome patients and families. We would like to hear your story and learn from you. But before that, we asked some scholars in the field to help us understand what 22q11.2 deletion syndrome is.

  2. Chromosome 22q11.2 deletion in a boy with Opitz (G/BBB) syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Fryburg, J.S.; Lin, K.Y.; Golden, W.L. [Univ. of Virginia Health Sciences Center, Charlottesville, VA (United States)

    1996-03-29

    This report is on a 14-month-old boy with manifestations of Opitz (G/BBB) syndrome in whom a 22q11.2 deletion was found. Deletion analysis was requested because of some findings in this patient reminiscent of velocardiofacial (VCF) syndrome. The extent of aspiration and of respiratory symptoms in this child is not usually seen in VCF syndrome. Opitz syndrome maps to at least two loci, one on Xp, the other on 22q11.2. 12 refs., 2 figs.

  3. 22q11.2 deletion carriers and schizophrenia-associated novel variants.

    Science.gov (United States)

    Balan, S; Iwayama, Y; Toyota, T; Toyoshima, M; Maekawa, M; Yoshikawa, T

    2014-01-01

    The penetrance of schizophrenia risk in carriers of the 22q11.2 deletion is high but incomplete, suggesting the possibility of additional genetic defects. We performed whole exome sequencing on two individuals with 22q11.2 deletion, one with schizophrenia and the other who was psychosis-free. The results revealed novel genetic variants related to neuronal function exclusively in the person with schizophrenia (frameshift: KAT8, APOH and SNX31; nonsense: EFCAB11 and CLVS2). This study paves the way towards a more complete understanding of variant dose and genetic architecture in schizophrenia.

  4. Visual processing deficits in 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Marjan Biria

    2018-01-01

    The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia.

  5. Detailed analysis of 22q11.2 with a high density MLPA probe set

    NARCIS (Netherlands)

    Jalali, G. R.; Vorstman, J. A. S.; Errami, Ab; Vijzelaar, R.; Biegel, J.; Shaikh, T.; Emanuel, B. S.

    The presence of chromosome-specific low-copy repeats (LCRs) predisposes chromosome 22 to deletions and duplications. The current diagnostic procedure for detecting aberrations at 22q11.2 is chromosomal analysis coupled with fluorescence in situ hybridization (FISH) or PCR-based multiplex ligation

  6. Yadav et al., Afr J Tradit Complement Altern Med. (2014) 11(2):249 ...

    African Journals Online (AJOL)

    cadewumi

    Yadav et al., Afr J Tradit Complement Altern Med. (2014) 11(2):249-256 ..... In recent years the popularity of complementary medicine has increased. Much interest has been focused on exploring ... delayed the induction of glucose intolerance and euglycemia in high fructose diet fed rats. Diabegon treatment inhibits the ...

  7. Prevalence of 22q11.2 deletions in 311 Dutch patients with schizophrenia

    NARCIS (Netherlands)

    Hoogendoorn, Mechteld L C; Vorstman, Jacob A S; Jalali, Gholam R; Selten, Jean-Paul; Sinke, Richard J; Emanuel, Beverly S; Kahn, René S

    UNLABELLED: The objectives of this study were 1) to examine whether the prevalence of 22q11.2 deletion syndrome (22q11DS) in schizophrenia patients with the Deficit syndrome is higher than the reported approximately 2% for the population of schizophrenia patients as a whole, and 2) to estimate the

  8. XP11.2 Translocation renal cell carcinoma: Clinical experience of Taipei Veterans General Hospital

    Directory of Open Access Journals (Sweden)

    Chia-Chen Hung

    2011-11-01

    Conclusion: Although RT-PCR and DNA sequencing are the final diagnoses of the molecular identity of Xp11.2 translocation RCC, experienced pathologists could confirm the histologic diagnosis based on the distinctive morphologic features with positive TFE3 immunochemical nuclear stain. Surgical resection is the only treatment. The role of systemic therapy for local recurrence and metastasis remains to be determined.

  9. Persistent Fifth Aortic Arch Associated with 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Meng-Luen Lee

    2006-01-01

    Conclusion: Congenital conotruncal malformations, including tetralogy of Fallot with pulmonary atresia or stenosis, and aortic arch anomalies including a persistent fifth aortic arch or a right aortic arch, should lead to suspicion of chromosome 22q11.2 deletion when manifested together with any one of the other four cardinal phenotypic features.

  10. Neuroimaging Correlates of 22q11.2 Deletion Syndrome: Implications for Schizophrenia Research

    NARCIS (Netherlands)

    Boot, E.; van Amelsvoort, T. A. M. J.

    2012-01-01

    22q11.2 Deletion syndrome (22q11DS) is the most common known recurrent copy-number variant disorder. It is also the most common known genetic risk factor for schizophrenia. The greater homogeneity of subjects with schizophrenia in 22q11DS compared with schizophrenia in the wider non-deleted

  11. Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions.

    Science.gov (United States)

    Demopoulos, Carly; Kothare, Hardik; Mizuiri, Danielle; Henderson-Sabes, Jennifer; Fregeau, Brieana; Tjernagel, Jennifer; Houde, John F; Sherr, Elliott H; Nagarajan, Srikantan S

    2018-01-19

    Speech and motor deficits are highly prevalent (>70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals.

  12. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

    DEFF Research Database (Denmark)

    Reinthaler, Eva M; Lal, Dennis; Lebon, Sebastien

    2014-01-01

    Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q1...

  13. Differentiated psychopharmacological treatment in three genetic subtypes of 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Egger, J.I.M.; Leeuw, N. de

    2017-01-01

    Introduction: The 22q11.2 deletion syndrome (22q11DS), mostly caused by the common deletion including the TBX- and COMT-genes (LCR22A-D), is highly associated with somatic anomalies. The distal deletion (distal of LCR22D) comprises the MAPK1-gene and is associated with specific heart defects. The

  14. Subtypes in 22q11.2 Deletion Syndrome Associated with Behaviour and Neurofacial Morphology

    Science.gov (United States)

    Sinderberry, Brooke; Brown, Scott; Hammond, Peter; Stevens, Angela F.; Schall, Ulrich; Murphy, Declan G. M.; Murphy, Kieran C.; Campbell, Linda E.

    2013-01-01

    22q11.2 deletion syndrome (22q11DS) has a complex phenotype with more than 180 characteristics, including cardiac anomalies, cleft palate, intellectual disabilities, a typical facial morphology, and mental health problems. However, the variable phenotype makes it difficult to predict clinical outcome, such as the high prevalence of psychosis among…

  15. Childhood Predictors of Young Adult Social Functioning in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Wagner, Kayla E.; Kates, Wendy R.; Fremont, Wanda; Antshel, Kevin M.

    2017-01-01

    The primary objectives of the current prospective longitudinal study were to (a) describe social functioning outcomes and (b) identify childhood predictors of social functioning in young adults with (22q11.2DS). Childhood predictors of young adult social functioning were examined. Family environment and parental stress in adolescence were…

  16. Primary lymphedema and other lymphatic anomalies are associated with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Unolt, Marta; Barry, Jessica; Digilio, Maria Cristina; Marino, Bruno; Bassett, Anne; Oechslin, Erwin; Low, David W; Belasco, Jean B; Kallish, Staci; Sullivan, Kathleen; Zackai, Elaine H; McDonald-McGinn, Donna M

    2018-02-12

    Lymphedema is an abnormal accumulation of interstitial fluid within the tissues. Primary lymphedema is caused by aberrant lymphangiogenesis and it has been historically classified based on age at presentation. Although most cases are sporadic, primary lymphedema may be familial or present in association with chromosomal abnormalities and syndromic disorders. To the best of our knowledge, primary lymphedema has never been described in patients with 22q11.2 deletion syndrome. We identified 4 patients with 22q11.2 deletion syndrome and primary lymphedema via our International 22q11.2 Deletion Syndrome Consortium. All patients underwent comprehensive clinical, laboratory and imaging assessments to rule out other causes of lymphedema. All patients had de novo typical deletions and family histories were negative for lymphedema. We report the novel association of primary lymphedema with 22q11.2 deletion syndrome. Importantly, animal models demonstrated Tbx1 playing a critical role in lymphangiogenesis by reducing Vegfr3 expression in lymphatic endothelial cells. Moreover, the VEGFR3 pathway is essential for lymphangiogenesis with mutations identified in hereditary primary lymphedema. Accordingly, our findings provide a new insight into understanding cellular mechanisms of lymphangiogenesis disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. Communication Disorders in the 22Q11.2 Microdeletion Syndrome.

    Science.gov (United States)

    Solot, Cynthia B.; Knightly, Carol; Handler, Steven D.; Gerdes, Marsha; McDonald-McGinn, Donna M.; Moss, Edward; Wang, Paul; Cohen, Marilyn; Randall, Peter; Larossa, Don; Driscoll, Deborah; Emanuel, Beverly S.; Zackai, Elaine H.

    2000-01-01

    The 22q11.2 microdeletion syndrome is a genetic disorder in children with many concomitant medical and developmental problems. Communication disorders are among the most common features of this syndrome and include articulation, language, resonance, and voice problems. Awareness of these features and a multidisciplinary approach are necessary for…

  18. Domain Specific Attentional Impairments in Children with Chromosome 22Q11.2 Deletion Syndrome

    Science.gov (United States)

    Bish, Joel P.; Chiodo, Renee; Mattei, Victoria; Simon, Tony J.

    2007-01-01

    One of the defining cognitive characteristics of the chromosome 22q deletion syndrome (DS22q11.2) is visuospatial processing impairments. The purpose of this study was to investigate and extend the specific attentional profile of children with this disorder using both an object-based attention task and an inhibition of return task. A group of…

  19. Core Neuropsychological Characteristics of Children and Adolescents with 22q11.2 Deletion

    Science.gov (United States)

    Jacobson, C.; Shearer, J.; Habel, A.; Kane, F.; Tsakanikos, E.; Kravariti, E.

    2010-01-01

    Background: The 22q11.2 deletion syndrome (22qDS) confers high risk for intellectual disability and neuropsychological/academic impairment, although a minority of patients show average intelligence. Intellectual heterogeneity and the high prevalence of psychiatric diagnoses in earlier studies may have obscured the prototypical neuropsychological…

  20. Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia.

    Science.gov (United States)

    Bassett, J K; Chandler, K E; Douzgou, S

    2016-08-01

    Chromosome 22q11.2 deletion syndrome is a clinically heterogeneous condition of intellectual disability, parathyroid and thyroid hypoplasia, palatal abnormalities, cardiac malformations and psychiatric symptoms. Hyperphagia and childhood obesity is widely reported in Prader-Willi Syndrome (PWS) but there is only one previous report of this presentation in chromosome 22q11.2 deletion syndrome. We describe two further cases of chromosome 22q11.2 deletion syndrome in which hyperphagia and childhood obesity were the presenting features. This may be a manifestation of obsessive behaviour secondary to some of the psychiatric features commonly seen in chromosome 22q11.2 deletion syndrome. Serious complications may result from hyperphagia and childhood obesity therefore early recognition and intervention is crucial. Due to the similar clinical presentation of these two patients to patients with PWS, it is suggested that the hyperphagia seen here should be managed in a similar way to how it is managed in PWS. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Mapping Cortical Morphology in Youth with Velocardiofacial (22q11.2 Deletion) Syndrome

    Science.gov (United States)

    Kates, Wendy R.; Bansal, Ravi; Fremont, Wanda; Antshel, Kevin M.; Hao, Xuejun; Higgins, Anne Marie; Liu, Jun; Shprintzen, Robert J.; Peterson, Bradley S.

    2011-01-01

    Objective: Velocardiofacial syndrome (VCFS; 22q11.2 deletion syndrome) represents one of the highest known risk factors for schizophrenia. Insofar as up to 30% of individuals with this genetic disorder develop schizophrenia, VCFS constitutes a unique, etiologically homogeneous model for understanding the pathogenesis of schizophrenia. Method:…

  2. Ocular Findings in Children With 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Gokturk, Bahar; Topcu-Yilmaz, Pinar; Bozkurt, Banu; Yildirim, Mahmut Selman; Guner, Sukru Nail; Sayar, Esra Hazar; Reisli, Ismail

    2016-07-01

    To identify the ocular features of children diagnosed as having 22q11.2 deletion syndrome in a Turkish population, which is the most common microdeletion syndrome with a wide range of facial and ocular abnormalities. Sixteen children aged between 4 months and 18 years with a microdeletion in chromosome 22q11.2 underwent a detailed ophthalmological examination including uncorrected and best corrected visual acuity testing, stereoscopic vision examination, biomicroscopic and indirect fundus examination, and ocular motility testing. All patients had at least one ocular abnormality. The major abnormalities were eyelid abnormalities (eye hooding, narrow palpebral fissure, telecanthus, hypertelorism, sparse and thin eyebrows and eyelashes, blepharitis, and distichiasis), posterior embryotoxon, and tortuous retinal vessels in at least half of the patients. Other ophthalmological disorders were refractive errors, iris remnants, and strabismus. The chromosome 22q11.2 deletion syndrome is associated with a wide range of ocular disorders, which necessitates a comprehensive eye examination for appropriate treatment and follow-up. Ocular findings sometimes can provide a clue to the diagnosis of 22q11.2 deletion. [J Pediatr Ophthalmol Strabismus. 2016;53(4):218-222]. Copyright 2016, SLACK Incorporated.

  3. Ocular findings in children with a microdeletion in chromosome 22q11.2.

    Science.gov (United States)

    Casteels, Ingele; Casaer, Patricia; Gewillig, Marc; Swillen, Ann; Devriendt, Koenraad

    2008-07-01

    A microdeletion in chromosome 22q11.2 is one of the most frequent genetic syndromes. The phenotypic manifestations vary widely, which has led to its initial description as apparently different clinical entities, such as the velocardiofacial syndrome (VCFS) and DiGeorge syndrome. Characteristic features include cleft palate, conotruncal heart malformations, thymus hypoplasia, hypoparathyroidism, a characteristic facial phenotype and learning difficulties. Ocular abnormalities are frequently seen in this patient population. We describe the ophthalmological findings in 36 children between the age of 3 and 14 years with a microdeletion in chromosome 22q11.2. They underwent a full ophthalmological examination with assessment of visual acuity, eye position and motility, stereoscopic vision, biomicroscopic examination, refraction and fundoscopy. If necessary amblyopia treatment was started and follow-up was planned. The presence of a cardiovascular malformation was noted. In conclusion, refractive errors, strabismus, amblyopia and structural ocular abnormalities are frequently encountered in children with a microdeletion in chromosome 22q11.2. Ophthalmological examination at a young age and refractive correction in those children is warranted. On the other hand, ocular findings can give a clue to the diagnosis of del 22q11.2.

  4. Co-occurrence of a de novo Williams and 22q11.2 microdeletion syndromes.

    Science.gov (United States)

    Shukla, Anju; Mandal, Kausik; Patil, Siddaramappa J; Kishore, Yougal; Phadke, Shubha R; Girisha, Katta M

    2015-08-01

    We report on a child with de novo deletions involving the 7q11.23 (Williams syndrome) and 22q11.2 (Velocardiofacial/DiGeorge syndrome) regions. We describe the clinical features of this rare double microdeletion syndrome reported here for the first time. © 2015 Wiley Periodicals, Inc.

  5. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Cascella, Marco; Muzio, Maria Rosaria

    2015-01-01

    Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Mathematical Learning Disabilities in Children with 22q11.2 Deletion Syndrome: A Review

    Science.gov (United States)

    De Smedt, Bert; Swillen, Ann; Verschaffel, Lieven; Ghesquiere, Pol

    2009-01-01

    Mathematical learning disabilities (MLD) occur frequently in children with specific genetic disorders, like Turner syndrome, fragile X syndrome and neurofibromatosis. This review focuses on MLD in children with chromosome 22q11.2 deletion syndrome (22q11DS). This syndrome is the most common known microdeletion syndrome with a prevalence of at…

  7. The cognitive development of children with the 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Duijff, S.N.

    2012-01-01

    Background: The 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with palatal abnormalities, cardiac defects and characteristic facial features. On a behavioural/ psychiatric level, children with 22q11DS are at an increased risk for various psychiatric problems, including Autism

  8. Genomic analysis of a xylose operon and characterization of novel xylose isomerase and xylulokinase from Bacillus coagulans NL01.

    Science.gov (United States)

    Zheng, Zhaojuan; Lin, Xi; Jiang, Ting; Ye, Weihua; Ouyang, Jia

    2016-08-01

    To investigate the xylose operon and properties of xylose isomerase and xylulokinase in Bacillus coagulans that can effectively ferment xylose to lactic acid. The xylose operon is widely present in B. coagulans. It is composed of four putative ORFs. Novel xylA and xylB from B. coagulans NL01 were cloned and expressed in Escherichia coli. Sequence of xylose isomerase was more conserved than that of xylulokinase. Both the enzymes exhibited maximum activities at pH 7-8 but with a high temperature maximum of 80-85 °C, divalent metal ion was prerequisite for their activation. Xylose isomerase and xylulokinase were most effectively activated by Ni(2+) and Co(2+), respectively. Genomic analysis of xylose operon has contributed to understanding xylose metabolism in B. coagulans and the novel xylose isomerase and xylulokinase might provide new alternatives for metabolic engineering of other strains to improve their fermentation performance on xylose.

  9. [Neurocognitive and psychiatric management of the 22q11.2 deletion syndrome].

    Science.gov (United States)

    Demily, C; Rossi, M; Schneider, M; Edery, P; Leleu, A; d'Amato, T; Franck, N; Eliez, S

    2015-06-01

    The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22. 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). The inheritance of the syndrome (10%) is autosomal dominant. Most people with 22q11.2DS are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. A small percentage of affected individuals have shorter deletions in the same region (contiguous gene deletion syndrome). The general features of 22q11.2DS vary widely (more than 180 phenotypic presentations) and the syndrome is under diagnosed. Characteristic symptoms may include congenital heart disease, defects in the palate, neuromuscular problems, velo-pharyngeal insufficiency, hypoparathyroidism, craniofacial features and problems with the immune system T-cell mediated response (caused by hypoplasia of the thymus). The neurocognitive phenotype of the 22q11.2DS is complex. Cognitive deficits are seen in the majority (80-100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory and visual-spatial perception. Borderline intellectual function (IQ: 70-75) is most common, mild intellectual disability (IQ: 55-75) is slightly less frequent and a small percentage of children fall into the low average intelligence range. Most children with 22q11.2DS achieve higher scores in verbal tasks than in non-verbal tasks, although this pattern of dysfunction being not universal. Brain MRI studies have shown volumetric changes in multiple cortical and subcortical regions in individuals with 22q11DS that could be related to both cognition and psychoses. General psychiatric features included anxiety disorders, attention deficit disorder and poor social skills (40-50%). An elevated risk of

  10. Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2-2q11.2.

    Science.gov (United States)

    Henden, Lyndal; Freytag, Saskia; Afawi, Zaid; Baldassari, Sara; Berkovic, Samuel F; Bisulli, Francesca; Canafoglia, Laura; Casari, Giorgio; Crompton, Douglas Ewan; Depienne, Christel; Gecz, Jozef; Guerrini, Renzo; Helbig, Ingo; Hirsch, Edouard; Keren, Boris; Klein, Karl Martin; Labauge, Pierre; LeGuern, Eric; Licchetta, Laura; Mei, Davide; Nava, Caroline; Pippucci, Tommaso; Rudolf, Gabrielle; Scheffer, Ingrid Eileen; Striano, Pasquale; Tinuper, Paolo; Zara, Federico; Corbett, Mark; Bahlo, Melanie

    2016-10-01

    Familial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder characterized by adult onset, involuntary muscle jerks, cortical myoclonus and occasional seizures. FAME is genetically heterogeneous with more than 70 families reported worldwide and five potential disease loci. The efforts to identify potential causal variants have been unsuccessful in all but three families. To date, linkage analysis has been the main approach to find and narrow FAME critical regions. We propose an alternative method, pedigree free identity-by-descent (IBD) mapping, that infers regions of the genome between individuals that have been inherited from a common ancestor. IBD mapping provides an alternative to linkage analysis in the presence of allelic and locus heterogeneity by detecting clusters of individuals who share a common allele. Succeeding IBD mapping, gene prioritization based on gene co-expression analysis can be used to identify the most promising candidate genes. We performed an IBD analysis using high-density single nucleotide polymorphism (SNP) array data followed by gene prioritization on a FAME cohort of ten European families and one Australian/New Zealander family; eight of which had known disease loci. By identifying IBD regions common to multiple families, we were able to narrow the FAME2 locus to a 9.78 megabase interval within 2p11.2-q11.2. We provide additional evidence of a founder effect in four Italian families and allelic heterogeneity with at least four distinct founders responsible for FAME at the FAME2 locus. In addition, we suggest candidate disease genes using gene prioritization based on gene co-expression analysis.

  11. 22q11.2 Deletion syndrome is associated with perioperative outcome in tetralogy of Fallot.

    Science.gov (United States)

    Mercer-Rosa, Laura; Pinto, Nelangi; Yang, Wei; Tanel, Ronn; Goldmuntz, Elizabeth

    2013-10-01

    We sought to investigate the impact of 22q11.2 deletion on perioperative outcome in tetralogy of Fallot. We conducted a retrospective review of patients with tetralogy of Fallot who underwent complete surgical reconstruction at The Children's Hospital of Philadelphia between 1995 and 2006. Inclusion criteria included diagnosis of tetralogy of Fallot and known genotype. Fisher exact and Mann-Whitney tests were used for categoric and continuous variables, respectively. Regression analysis was used to determine whether deletion status predicts outcome. We studied 208 subjects with tetralogy of Fallot, 164 (79%) without and 44 (20%) with 22q11.2 deletion syndrome. There were no differences in sex, race, gestational age, age at diagnosis, admission weight, and duration of mechanical ventilation. Presenting anatomy, survival, complications and reoperations were also comparable between patients with and without 22q11.2 deletion syndrome. Those with 22q11.2 deletion syndrome had more aortopulmonary shunts preceding complete surgical repair (21% vs 7%, P = .02). This association was present after adjustment for presenting anatomy (stenosis, atresia, or absence of pulmonary valve and common atrioventricular canal) and surgical era. In addition, those with 22q11.2 deletion syndrome had longer cardiopulmonary bypass time (84 vs 72 minutes, P = .02) and duration of intensive care (6 vs 4 days, P = .007). Genotype affects early operative outcomes in tetralogy of Fallot resulting, in particular, in longer duration of intensive care. Future studies are required to determine factors contributing to such differences in this susceptible population. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  12. Fluency aspects of oral narrative task in del22q11.2 syndrome.

    Science.gov (United States)

    Santos, Amanda Oliveira; Rossi, Natalia Freitas; Tandel, Maria da Conceição Faria Freitas; Richieri-Costa, Antonio; Giacheti, Célia Maria

    2016-01-01

    To investigate the fluency aspects of the oral narrative task in individuals with del22q11.2 syndrome and compare them with those of individuals with typical language development. Fifteen individuals diagnosed with del22q11.2 syndrome, both genders, aged 7-17 years participated in this study. They were compared with 15 individuals with typical language development, with similar gender and chronological age profiles. The oral narrative was elicited using the book "Frog, Where Are You?", and the fluency aspects were analyzed according to speech rate and type and frequency of disfluency (typical and stuttering). The number and duration of pauses were also investigated. The data were statistically analyzed. The group with del22q11.2 syndrome showed a higher average when compared with the group without the syndrome for the percentage of typical disfluencies, mainly hesitation and revision. The group presenting the syndrome also showed a higher average for stuttering disfluencies, with pause as the most frequent disfluency. With respect to speech rate, the group with the syndrome presented a lower average for the number of words and syllables per minute. Individuals with del22q11.2 syndrome showed greater difficulties of narration than their peers. The fluency aspects of the oral narrative task in subjects with del22q11.2 syndrome were similar to those of individuals with typical language development regarding the presence of hesitation, revision, and pause, but they were different with respect to frequency of disfluency, which was higher in individuals with the syndrome.

  13. Otologic and audiologic findings in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Verheij, E; Kist, A L; Mink van der Molen, A B; Stegeman, I; van Zanten, G A; Grolman, W; Thomeer, H G X M

    2017-02-01

    Hearing loss is frequently present in the 22q11.2 deletion syndrome. Our aim was to describe the audiologic and otologic features of patients with 22q11.2 deletion syndrome. We conducted a retrospective cohort study in a single tertiary referral center. We reviewed medical files of all patients with 22q11.2 deletion syndrome who visited an otolaryngologist, plastic surgeon or speech therapist, for audiologic or otologic features. Hearing loss was defined as a pure tone average (of 0.5, 1, 2, and 4 kHz) of >20 decibel hearing level. Audiograms were available for 102 of 199 included patients, out of which 163 ears were measured in the required frquencies (0.5-4 kHz). Median age at time of most recent audiogram was 7 years (range 3-29 years). In 62 out of 163 ears (38%), hearing loss was present. Most ears had conductive hearing loss (n = 58) and 4 ears had mixed hearing loss. The severity of hearing loss was most frequently mild (pure tone average of ≤40 decibel hearing level). In 22.5% of ears, otitis media with effusion was observed at time of most recent audiogram. Age was not related to mean air conduction hearing thresholds or to otitis media with effusion (p = 0.43 and p = 0.11, respectively). In conclusion, hearing loss and otitis media are frequently present in patients with 22q11.2 deletion syndrome. Moreover, our results suggest that children with 22q11.2 deletion syndrome remain susceptible for otitis media as they age.

  14. The Impact of 22q11.2 Microdeletion on Cardiac Surgery Postoperative Outcome.

    Science.gov (United States)

    Cuturilo, Goran; Drakulic, Danijela; Jovanovic, Ida; Ilic, Slobodan; Kalanj, Jasna; Vulicevic, Irena; Raus, Misela; Skoric, Dejan; Mijovic, Marija; Medjo, Biljana; Rsovac, Snezana; Stevanovic, Milena

    2017-12-01

    22q11.2 microdeletion is the most common microdeletion in humans. The purpose of this study was to evaluate postoperative outcome in children with 22q11.2 microdeletion who had undergone complete surgical correction of a congenital heart defect. The study included 34 patients who underwent complete correction of conotruncal heart defects. Of these, 17 patients diagnosed with 22q11.2 microdeletion represent the investigated group. Another 17 patients without 22q11.2 microdeletion represent the control group. Investigated and control groups differ significantly for total length of stay in the hospital (average 37.35 and 14.12 days, respectively); length of postoperative stay in the intensive care unit (average 10.82 and 6.76 days, respectively); sepsis (eight and two patients, respectively); administration of antibiotics (15 and seven patients, respectively); duration of antibiotic therapy (average 17.65 and 14.59 days, respectively); occurrence of hypocalcemia (16 and 0 patients, respectively); and initiation of peroral nutrition during the postoperative course (average 10.29 and 3.88 days, respectively). No difference was found for duration of ventilatory support (average 6.12 and 4.24 days, respectively), administration of total parenteral nutrition, and postoperative mortality rate. The study results suggest that genotype of 22q11.2 microdeletion affects postoperative outcome after cardiac surgery. Possible targets for intervention in postoperative intensive care management are prevention and treatment of systemic infections, monitoring, and treatment of hypocalcemias, rational administration of antibiotics and careful planning of nutrition. Consequently, this could shorten patients' intensive care stay and overall duration of hospitalization.

  15. 19 CFR 11.2a - Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers...

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Release from Customs custody without payment of tax on cigars, cigarettes and cigarette papers and tubes. 11.2a Section 11.2a Customs Duties U.S... STAMPING; MARKING Packing and Stamping § 11.2a Release from Customs custody without payment of tax on...

  16. 16p11.2 Deletion Mice Display Cognitive Deficits in Touchscreen Learning and Novelty Recognition Tasks

    Science.gov (United States)

    Yang, Mu; Lewis, Freeman C.; Sarvi, Michael S.; Foley, Gillian M.; Crawley, Jacqueline N.

    2015-01-01

    Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2

  17. Maladaptive Conflict Monitoring as Evidence for Executive Dysfunction in Children with Chromosome 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Bish, Joel P.; Ferrante, Samantha M.; McDonald-McGinn, Donna; Zackai, Elaine; Simon, Tony J.

    2005-01-01

    Using an adaptation of the Attentional Networks Test, we investigated aspects of executive control in children with chromosome 22q11.2 deletion syndrome (DS22q11.2), a common but not well understood disorder that produces non-verbal cognitive deficits and a marked incidence of psychopathology. The data revealed that children with DS22q11.2

  18. Fen Bilgisi Öğretmen Adaylarının Kimya Bilgilerini Günlük Hayatla İlişkilendirebilme Düzeyleri

    OpenAIRE

    Yadigaroğlu, Yrd. Doç. Dr. Mustafa; DEMİRCİOĞLU, Doç. Dr. Gökhan; DEMİRCİOĞLU, Doç. Dr. Hülya

    2017-01-01

    Fen eğitiminin temel amaçlarındanbiri, öğrencilerin fen okur-yazarı olmalarını sağlayarak onları günlükyaşantılarında karşılaştıkları fen olaylarına anlam vermelerine yardımcıolmaktır. Günlük hayatla ya da bağlamı ile ilişkilendirilmeyen bilgi öğrencininzihninde her zaman eksik olacaktır. Bunun gerçekleştirilmesinde fen dersleriiçerisinde yer alan kimya önemli bir yere sahiptir. Bu düşünceden hareketleçalışmada, fen bilgisi öğretmen adaylarının kimya bilgilerini günlük hayatlailişkilendirebil...

  19. Evans syndrome and antibody deficiency: an atypical presentation of chromosome 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Gloria Colarusso

    2010-06-01

    Full Text Available We report a case of an 8-year-old male patient with Evans syndrome and severe hypogammaglobulinemia, subsequently in whom the 22q11.2 deletion syndrome (22q11.2 DS was diagnosed. No other clinical sign of 22q11.2 DS was present with the exception of slight facial dysmorphism. The case is of particular interest because it suggests the need to research chromosome 22q11.2 deletion in patients who present with autoimmune cytopenia and peculiar facial abnormalities, which could be an atypical presentation of an incomplete form of 22q11.2 DS.

  20. How to diagnose the 22q11.2 deletion syndrome in patients with schizophrenia: a case report

    OpenAIRE

    Ohi, Kazutaka; Hashimoto, Ryota; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Nakatani, Noriko; Kamino, Kouzin; Takeda, Masatoshi

    2013-01-01

    The 22q11.2 deletion syndrome is caused by a microdeletion of chromosome 22. One third of all patients with 22q11.2 deletion develop schizophrenia-like symptoms. In general, the prevalence of 22q11.2 deletion in patients with schizophrenia is 1%?2%. The 22q11.2 deletion is one of the major known genetic risk factors for schizophrenia. However, clinical differences in the phenotypes between patients with schizophrenia who are 22q11.2 deletion carriers and those who are not are still unknown. T...

  1. [Identification of 22q11.2 microdeletion among patients with congenital heart diseases using droplet digital PCR].

    Science.gov (United States)

    Zhou, Xiangcheng; Zhang, Cuicui; Li, Mi; Ma, Jian; Chen, Qiuping; Sun, Shanquan; Zhang, Liang

    2018-02-10

    OBJECTIVE To develop a new method for detecting 22q11.2 deletion syndrome (22q11.2 DS) in clinical settings. METHODS Specific primers and fluorescence probes were designed to target the TBX1 gene within the 22q11.2 deletion region and a reference gene RPP30. Multiplexed droplet digital PCR (ddPCR) was run to detect the 22q11.2 microdeletion by calculating the ratio of positive droplet number of TBX1/RPP30. RESULTS Three cases of 22q11.2 microdeletion previously confirmed by array comparative genome hybridization were successfully identified. Subsequently, the ddPCR detected two further cases of 22q11.2 microdeletion among 14 children with congenital heart diseases. CONCLUSION The ddPCR technique has provided a rapid and cost-effective method for detecting 22q11.2 microdeletion in clinical settings.

  2. Multitasking Abilities in Adolescents With 22q11.2 Deletion Syndrome: Results From an Experimental Ecological Paradigm.

    Science.gov (United States)

    Schneider, Maude; Eliez, Stephan; Birr, Julie; Menghetti, Sarah; Debbané, Martin; Van der Linden, Martial

    2016-03-01

    The 22q11.2 deletion syndrome (22q11.2DS) is associated with cognitive and functional impairments and increased risk for schizophrenia. We characterized multitasking abilities of adolescents with 22q11.2DS using an experimental naturalistic setting and examined whether multitasking impairments were associated with real-world functioning and negative symptoms. Thirty-nine adolescents (19 with 22q11.2DS and 20 controls) underwent the Multitasking Evaluation for Adolescents. Real-world functioning and clinical symptoms were assessed in participants with 22q11.2DS. Adolescents with 22q11.2DS performed poorly in the multitasking evaluation. Our data also suggest that multitasking abilities are related to adaptive functioning in the practical domain and negative symptoms. This study shows that adolescents with 22q11.2DS are characterized by multitasking impairments, which may be relevant for several aspects of the clinical phenotype.

  3. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

    DEFF Research Database (Denmark)

    Horne, Hisani N; Chung, Charles C; Zhang, Han

    2016-01-01

    The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking...... rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120......,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry...

  4. Altered auditory processing and effective connectivity in 22q11.2 deletion syndrome

    DEFF Research Database (Denmark)

    Larsen, Kit Melissa; Mørup, Morten; Birknow, Michelle Rosgaard

    2018-01-01

    11.2 deletion carriers. DCM showed reduced intrinsic connection within right primary auditory cortex as well as in the top-down, connection from the right inferior frontal gyrus to right superior temporal gyrus for 22q11.2 deletion carriers although not surviving correction for multiple comparison....... Mismatch negativity (MMN), a brain marker of change detection, is reduced in people with schizophrenia compared to healthy controls. Using dynamic causal modelling (DCM), previous studies showed that top-down effective connectivity linking the frontal and temporal cortex is reduced in schizophrenia......-carriers with comparable age distribution and sex ratio, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Despite finding no significant reduction in the MMN responses, whole-scalp spatiotemporal analysis of responses to the tones revealed a greater fronto-temporal N1 component in the 22q...

  5. A child with chromosome 22q11.2 deletion syndrome and a bilobed gallbladder

    Energy Technology Data Exchange (ETDEWEB)

    Clarke, James R.; Macken, Marian B. [Dalhousie University, Department of Radiology, Halifax, Nova Scotia (Canada); Schmidt, Matthias H. [Dalhousie University, Department of Radiology, Halifax, Nova Scotia (Canada); IWK Health Centre, Department of Diagnostic Imaging, 5850/5980 University Ave., P.O. Box 9700, Halifax, Nova Scotia (Canada); Morley, Charlotte; Cummings, Elizabeth A. [Dalhousie University, Department of Pediatrics, Halifax, Nova Scotia (Canada)

    2007-02-15

    We present an 11-year-old girl with a chromosome 22q11.2 microdeletion, velocardiofacial syndrome (VCFS), and a bilobed gallbladder as an incidental finding on abdominal sonography. The finding was confirmed by magnetic resonance cholangiopancreatography (MRCP).This is the first report of a gallbladder anomaly associated with a chromosome 22q11.2 deletion and the second report of a biliary tract anomaly associated with a mutation in the chromosome 22q11 region. We suggest that close attention be paid to the anatomy of the biliary tree in patients with mutations in the chromosome 22q11 region. Further study is warranted to determine the range and prevalence of biliary tract anomalies in this population. (orig.)

  6. A Turkish patient with large 17p11.2 deletion presenting with Smith Magenis syndrome.

    Science.gov (United States)

    Tug, E; Cine, N; Aydin, H

    2011-01-01

    Smith-Magenis syndrome (SMS), which occurs as a result of an interstitial deletion within chromosome 17p11.2-p12, is a disorder that presents itself with minor dysmorphic features, brachydactyly, short stature, hypotonia, delayed speech, cognitive deficits and neurobehavioral problems including sleep disturbances and maladaptive repetitive and self-injurious behavior. We present a girl with full SMS phenotype. G-banding cytogenetic analysis showed normal 46,XX karyotype. Whole-genome array comparative genomic hybridization (CGH) was performed due to the severity of the phenotype and the unusual features present in the patient. An interstitial deletion in 17p11.2-p12, approximately 4.73 Mb in size was determined. Characteristic physical and behavioral phenotype strongly suggested SMS. This, to the best of our knowledge is the first patient with SMS reported in Turkey. We emphasize the need for whole genome analysis in multiple congenital abnormalities/mental retardation disorders with unusual and severe phenotypes.

  7. Social Cognition as a Predictor of Psychotic Symptoms in 22q11.2 Microdeletion Syndrome

    OpenAIRE

    Jalbrzikowski, Maria Elizabeth

    2013-01-01

    22q11.2 Microdeletion syndrome (22qDS) is caused by a recurrent genetic mutation associated with a high degree of social impairment, and also represents one of the greatest known genetic risk factors for schizophrenia. This syndrome therefore represents an excellent model for investigating how a known genetic "lesion" may lead to abnormal development of social behavior and to the expression of a diagnosable psychotic disorder. However, little is known about vulnerabilities that contribute to...

  8. Association and mutation analyses of 16p11.2 autism candidate genes.

    Directory of Open Access Journals (Sweden)

    Ravinesh A Kumar

    Full Text Available Autism is a complex childhood neurodevelopmental disorder with a strong genetic basis. Microdeletion or duplication of a approximately 500-700-kb genomic rearrangement on 16p11.2 that contains 24 genes represents the second most frequent chromosomal disorder associated with autism. The role of common and rare 16p11.2 sequence variants in autism etiology is unknown.To identify common 16p11.2 variants with a potential role in autism, we performed association studies using existing data generated from three microarray platforms: Affymetrix 5.0 (777 families, Illumina 550 K (943 families, and Affymetrix 500 K (60 families. No common variants were identified that were significantly associated with autism. To look for rare variants, we performed resequencing of coding and promoter regions for eight candidate genes selected based on their known expression patterns and functions. In total, we identified 26 novel variants in autism: 13 exonic (nine non-synonymous, three synonymous, and one untranslated region and 13 promoter variants. We found a significant association between autism and a coding variant in the seizure-related gene SEZ6L2 (12/1106 autism vs. 3/1161 controls; p = 0.018. Sez6l2 expression in mouse embryos was restricted to the spinal cord and brain. SEZ6L2 expression in human fetal brain was highest in post-mitotic cortical layers, hippocampus, amygdala, and thalamus. Association analysis of SEZ6L2 in an independent sample set failed to replicate our initial findings.We have identified sequence variation in at least one candidate gene in 16p11.2 that may represent a novel genetic risk factor for autism. However, further studies are required to substantiate these preliminary findings.

  9. Periventricular nodular heterotopia and bilateral intraventricular xanthogranulomas in 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Moogeh Baharnoori

    2017-09-01

    Full Text Available 22q11.2 deletion syndrome (22q11DS is the most common pathogenic copy number variant in humans. Neuropsychiatric phenotypes, including schizophrenia, are prominent. Imaging studies of individuals with this syndrome show a variety of abnormalities that may indicate abnormal neuronal migration. Here we present the neuroimaging and neuropathologic features of a 22q11DS patient with bilateral periventricular nodular heterotopias (PNH and intraventricular xanthogranulomas that were identified by post-mortem examination.

  10. Subthreshold Psychosis in 22q11.2 Deletion Syndrome: Multisite Naturalistic Study.

    Science.gov (United States)

    Weisman, Omri; Guri, Yael; Gur, Raquel E; McDonald-McGinn, Donna M; Calkins, Monica E; Tang, Sunny X; Emanuel, Beverly; Zackai, Elaine H; Eliez, Stephan; Schneider, Maude; Schaer, Marie; Kates, Wendy R; Antshel, Kevin M; Fremont, Wanda; Shashi, Vandana; Hooper, Stephen R; Armando, Marco; Vicari, Stefano; Pontillo, Maria; Kushan, Leila; Jalbrzikowski, Maria; Bearden, Carrie E; Cubells, Joseph F; Ousley, Opal Y; Walker, Elaine F; Simon, Tony J; Stoddard, Joel; Niendam, Tara A; van den Bree, Marianne B M; Gothelf, Doron

    2017-09-01

    Nearly one-third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop a psychotic disorder during life, most of them by early adulthood. Importantly, a full-blown psychotic episode is usually preceded by subthreshold symptoms. In the current study, 760 participants (aged 6-55 years) with a confirmed hemizygous 22q11.2 microdeletion have been recruited through 10 medical sites worldwide, as part of an international research consortium. Of them, 692 were nonpsychotic and with complete measurement data. Subthreshold psychotic symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). Nearly one-third of participants met criteria for positive subthreshold psychotic symptoms (32.8%), less than 1% qualified for acute positive subthreshold symptoms, and almost a quarter met criteria for negative/disorganized subthreshold symptoms (21.7%). Adolescents and young adults (13-25 years) showed the highest rates of subthreshold psychotic symptoms. Additionally, higher rates of anxiety disorders and attention deficit/hyperactivity disorder (ADHD) were found among the study participants with subthreshold psychotic symptoms compared to those without. Full-scale IQ, verbal IQ, and global functioning (GAF) scores were negatively associated with participants' subthreshold psychotic symptoms. This study represents the most comprehensive analysis reported to date on subthreshold psychosis in 22q11.2DS. Novel findings include age-related changes in subthreshold psychotic symptoms and evidence that cognitive deficits are associated with subthreshold psychosis in this population. Future studies should longitudinally follow these symptoms to detect whether and how early identification and treatment of these manifestations can improve long-term outcomes in those that eventually develop a psychotic disorder. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For

  11. Evaluation of 22q11.2 deletion in Cleft Palate patients

    Science.gov (United States)

    Prabodha, L. B. Lahiru; Dias, Dayanath Kumara; Nanayakkara, B. Ganananda; de Silva, Deepthi C.; Chandrasekharan, N. Vishvanath; Ileyperuma, Isurani

    2012-01-01

    Background: Cleft palate is the commonest multifactorial epigenetic disorder with a prevalence of 0.43-2.45 per 1000. The objectives of this study were to evaluate the clinical features and identify the 22q11.2 deletion in patients with cleft palate in Sri Lanka. Materials and Methods: Cleft patients attending a Teaching Hospital in Sri Lanka were recruited for this study. The relevant data were obtained from review of case notes, interviews, and examination of patients according to a standard evaluation sheet. Quantitative multiplex polymerase chain reaction (PCR) was performed to identify the 22q11.2 deletion. A gel documentation system (Bio-Doc) was used to quantify the PCR product following electrophoresis on 0.8% agarose gel. Results and Conclusion: There were 162 cleft palate patients of whom 59% were females. A total of 92 cleft palate subjects (56.2%) had other associated clinical features. Dysmorphic features (25.27%) and developmental delays (25.27%) were the commonest medical problems encountered. The cleft was limited to the soft palate in 125 patients, while in 25 patients it involved both the hard and the soft palate. There were seven subjects with bifid uvula and five subjects with submucous cleft palate. None of the patients had 22q11.2 deletion in this study population. A multicentered large population-based study is needed to confirm the results of this study and to develop guidelines on the appropriate use of 22q11.2 deletion testing, which are valid for cleft palate patients in Sri Lanka. PMID:23483617

  12. 16p11.2 Locus modulates response to satiety before the onset of obesity.

    Science.gov (United States)

    Maillard, A M; Hippolyte, L; Rodriguez-Herreros, B; Chawner, S J R A; Dremmel, D; Agüera, Z; Fagundo, A B; Pain, A; Martin-Brevet, S; Hilbert, A; Kurz, S; Etienne, R; Draganski, B; Jimenez-Murcia, S; Männik, K; Metspalu, A; Reigo, A; Isidor, B; Le Caignec, C; David, A; Mignot, C; Keren, B; van den Bree, M B M; Munsch, S; Fernandez-Aranda, F; Beckmann, J S; Reymond, A; Jacquemont, S

    2016-05-01

    The 600 kb BP4-BP5 copy number variants (CNVs) at the 16p11.2 locus have been associated with a range of neurodevelopmental conditions including autism spectrum disorders and schizophrenia. The number of genomic copies in this region is inversely correlated with body mass index (BMI): the deletion is associated with a highly penetrant form of obesity (present in 50% of carriers by the age of 7 years and in 70% of adults), and the duplication with being underweight. Mechanisms underlying this energy imbalance remain unknown. This study aims to investigate eating behavior, cognitive traits and their relationships with BMI in carriers of 16p11.2 CNVs. We assessed individuals carrying a 16p11.2 deletion or duplication and their intrafamilial controls using food-related behavior questionnaires and cognitive measures. We also compared these carriers with cohorts of individuals presenting with obesity, binge eating disorder or bulimia. Response to satiety is gene dosage-dependent in pediatric CNV carriers. Altered satiety response is present in young deletion carriers before the onset of obesity. It remains altered in adolescent carriers and correlates with obesity. Adult deletion carriers exhibit eating behavior similar to that seen in a cohort of obesity without eating disorders such as bulimia or binge eating. None of the cognitive measures are associated with eating behavior or BMI. These findings suggest that abnormal satiety response is a strong contributor to the energy imbalance in 16p11.2 CNV carriers, and, akin to other genetic forms of obesity, altered satiety responsiveness in children precedes the increase in BMI observed later in adolescence.

  13. Epilepsy in 22q11.2 Deletion Syndrome: A Case Series and Literature Review.

    Science.gov (United States)

    Mudigoudar, Basanagoud; Nune, Sunitha; Fulton, Stephen; Dayyat, Ehab; Wheless, James W

    2017-11-01

    The 22q11.2 deletion syndrome affects multiple organ systems, and the neurological manifestations are an important aspect of this disorder. Many are aware of cardiac anomalies associated with this uncommon genetic disorder. However, the different types of seizures, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) findings seen in this condition are not appreciated. Medical records of four patients with epilepsy due to 22q11.2 deletion syndrome were retrospectively reviewed for documentation of seizure types, EEG, and brain MRI findings. In addition, we also did a literature review of previously reported individuals with unprovoked seizures in this condition. A review of all published cases including our patients reveals that focal epilepsy (39 of 88, 44%) is the most common type followed by genetic generalized epilepsy (24 of 88, 27%). Diffuse cerebral atrophy and polymicrogyria were the most frequent MRI findings. Patients with structural brain abnormalities, especially polymicrogyria and associated epilepsy should have a chromosomal microarray (CMA) performed to screen for the 22q11.2 deletion syndrome. Focal epilepsy and genetic generalized epilepsy are the most frequent epilepsy types reported in this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. SNP Microarray in FISH Negative Clinically Suspected 22q11.2 Microdeletion Syndrome

    Science.gov (United States)

    Jain, Manish; Kalsi, Amanpreet Kaur

    2016-01-01

    The present study evaluated the role of SNP microarray in 101 cases of clinically suspected FISH negative (noninformative/normal) 22q11.2 microdeletion syndrome. SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or CytoScan 750 K array. SNP microarray identified 8 cases of 22q11.2 microdeletions and/or microduplications in addition to cases of chromosomal abnormalities and other pathogenic/likely pathogenic CNVs. Clinically suspected specific deletions (22q11.2) were detectable in approximately 8% of cases by SNP microarray, mostly from FISH noninformative cases. This study also identified several LOH/AOH loci with known and well-defined UPD (uniparental disomy) disorders. In conclusion, this study suggests more strict clinical criteria for FISH analysis. However, if clinical criteria are few or doubtful, in particular newborn/neonate in intensive care, SNP microarray should be the first screening test to be ordered. FISH is ideal test for detecting mosaicism, screening family members, and prenatal diagnosis in proven families. PMID:27051557

  15. Variable immune deficiency related to deletion size in chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Crowley, Blaine; Ruffner, Melanie; McDonald McGinn, Donna M; Sullivan, Kathleen E

    2018-01-17

    The clinical features of 22q11.2 deletion syndrome include virtually every organ of the body. This review will focus on the immune system and the differences related to deletion breakpoints. A hypoplastic thymus was one of the first features described in this syndrome and low T cell counts, as a consequence of thymic hypoplasia, are the most commonly described immunologic feature. These are most prominently seen in early childhood and can be associated with increased persistence of viruses. Later in life, evidence of T cell exhaustion may be seen and secondary deficiencies of antibody function have been described. The relationship of the immunodeficiency to the deletion breakpoints has been understudied due to the infrequent analysis of people carrying smaller deletions. This manuscript will review the immune deficiency in 22q11.2 deletion syndrome and describe differences in the T cell counts related to the deletion breakpoints. Distal, non-TBX1 inclusive deletions, were found to be associated with better T cell counts. Another new finding is the relative preservation of T cell counts in those patients with a 22q11.2 duplication. © 2018 Wiley Periodicals, Inc.

  16. SNP Microarray in FISH Negative Clinically Suspected 22q11.2 Microdeletion Syndrome.

    Science.gov (United States)

    Halder, Ashutosh; Jain, Manish; Kalsi, Amanpreet Kaur

    2016-01-01

    The present study evaluated the role of SNP microarray in 101 cases of clinically suspected FISH negative (noninformative/normal) 22q11.2 microdeletion syndrome. SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or CytoScan 750 K array. SNP microarray identified 8 cases of 22q11.2 microdeletions and/or microduplications in addition to cases of chromosomal abnormalities and other pathogenic/likely pathogenic CNVs. Clinically suspected specific deletions (22q11.2) were detectable in approximately 8% of cases by SNP microarray, mostly from FISH noninformative cases. This study also identified several LOH/AOH loci with known and well-defined UPD (uniparental disomy) disorders. In conclusion, this study suggests more strict clinical criteria for FISH analysis. However, if clinical criteria are few or doubtful, in particular newborn/neonate in intensive care, SNP microarray should be the first screening test to be ordered. FISH is ideal test for detecting mosaicism, screening family members, and prenatal diagnosis in proven families.

  17. 22q11.2 microdeletion in two adolescent patients who presented with convulsion.

    Science.gov (United States)

    Özkale, Murat; Erol, İlknur

    2014-03-01

    22q11.2 microdeletion which involves DiGeorge syndrome, velo-cardiofacial syndrome and conotruncal anomaly face syndrome occurs as a result of a deletion in the short segment of the long arm of the 22th chromosome. Patients with this syndrome have a wide clinical spectrum including learning difficulty, dysmorphic face, cardiac anomalies, hypocalcemia, hypoparathyroidism, cleft palate, thymus anomalies, immune failure and speech and feeding problems. The number of clinical characteristics which have been reported to be related with this syndrome is higher than 180. All anomalies may not be present in all patients. In this article, a 12-year old female patient who was found to have 22q11.2 microdeletion with mild mental retardation and dysmorphic face and who presented to our hospital because of convulsion and a 13-year old male patient who was found to have 22q11.2 microdeletion with hypocalcemia, hypoparathyroidism, dysmorphic face and mental retardation and who presented to our hospital because of convulsion (it was learned from his history that he was being followed up in another center because of autism) were presented.

  18. Abnormal auditory and language pathways in children with 16p11.2 deletion

    Directory of Open Access Journals (Sweden)

    Jeffrey I. Berman

    2015-01-01

    Full Text Available Copy number variations at chromosome 16p11.2 contribute to neurodevelopmental disorders, including autism spectrum disorder (ASD. This study seeks to improve our understanding of the biological basis of behavioral phenotypes common in ASD, in particular the prominent and prevalent disruption of spoken language seen in children with the 16p11.2 BP4–BP5 deletion. We examined the auditory and language white matter pathways with diffusion MRI in a cohort of 36 pediatric deletion carriers and 45 age-matched controls. Diffusion MR tractography of the auditory radiations and the arcuate fasciculus was performed to generate tract specific measures of white matter microstructure. In both tracts, deletion carriers exhibited significantly higher diffusivity than that of controls. Cross-sectional diffusion parameters in these tracts changed with age with no group difference in the rate of maturation. Within deletion carriers, the left-hemisphere arcuate fasciculus mean and radial diffusivities were significantly negatively correlated with clinical language ability, but not non-verbal cognitive ability. Diffusion metrics in the right-hemisphere arcuate fasciculus were not predictive of language ability. These results provide insight into the link between the 16p11.2 deletion, abnormal auditory and language pathway structures, and the specific behavioral deficits that may contribute to neurodevelopmental disorders such as ASD.

  19. SNP Microarray in FISH Negative Clinically Suspected 22q11.2 Microdeletion Syndrome

    Directory of Open Access Journals (Sweden)

    Ashutosh Halder

    2016-01-01

    Full Text Available The present study evaluated the role of SNP microarray in 101 cases of clinically suspected FISH negative (noninformative/normal 22q11.2 microdeletion syndrome. SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or CytoScan 750 K array. SNP microarray identified 8 cases of 22q11.2 microdeletions and/or microduplications in addition to cases of chromosomal abnormalities and other pathogenic/likely pathogenic CNVs. Clinically suspected specific deletions (22q11.2 were detectable in approximately 8% of cases by SNP microarray, mostly from FISH noninformative cases. This study also identified several LOH/AOH loci with known and well-defined UPD (uniparental disomy disorders. In conclusion, this study suggests more strict clinical criteria for FISH analysis. However, if clinical criteria are few or doubtful, in particular newborn/neonate in intensive care, SNP microarray should be the first screening test to be ordered. FISH is ideal test for detecting mosaicism, screening family members, and prenatal diagnosis in proven families.

  20. Ras Labs-CASIS-ISS NL experiment for synthetic muscle returned to Earth: resistance to ionizing radiation

    Science.gov (United States)

    Rasmussen, Lenore; Albers, Leila N.; Rodriguez, Simone; Gentile, Charles; Meixler, Lewis D.; Ascione, George; Hitchner, Robert; Taylor, James; Hoffman, Dan; Cylinder, David; Gaza, Ramona; Moy, Leon; Mark, Patrick S.; Prillaman, Daniel L.; Nodarse, Robert; Menegus, Michael J.; Ratto, Jo Ann; Thellen, Christopher T.; Froio, Danielle; Valenza, Logan; Poirier, Catherine; Sinkler, Charles; Corl, Dylan; Hablani, Surbhi; Fuerst, Tyler; Gallucci, Sergio; Blocher, Whitney; Liffland, Stephanie

    2017-04-01

    In anticipation of deep space travel, new materials are being explored to assist and relieve humans in dangerous environments, such as high radiation, extreme temperature, and extreme pressure. Ras Labs Synthetic Muscle™ - electroactive polymers (EAPs) that contract and expand at low voltages - which mimic the unique gentle-yet-strong nature of human tissue, is a potential asset to manned space travel through protective gear and human assist robotics and for unmanned space exploration through deep space. Gen 3 Synthetic Muscle™ was proven to be resistant to extreme temperatures, and there were indications that these materials would also be radiation resistant. The purpose of the Ras Labs-CASIS-ISS Experiment was to test the radiation resistivity of the third and fourth generation of these EAPs, as well as to make them even more radiation resistant. On Earth, exposure of the Generation 3 and Generation 4 EAPs to a Cs-137 radiation source for 47.8 hours with a total dose of 305.931 kRad of gamma radiation was performed at the US Department of Energy's Princeton Plasma Physics Laboratory (PPPL) at Princeton University, followed by pH, peroxide, Shore Hardness durometer, and electroactivity testing to determine the inherent radiation resistivity of these contractile EAPs, and to determine whether the EAPs could be made even more radiation resistant through the application of appropriate additives and coatings. The on Earth preliminary tests determined that selected Ras Labs EAPs were not only inherently radiation resistant, but with the appropriate coatings and additives, could be made even more radiation resistant. G-force testing to over 10 G's was performed at US Army's ARDEC Labs, with excellent results, in preparation for space flight to the International Space Station National Laboratory (ISS-NL). Selected samples of Generation 3 and Generation 4 Synthetic Muscle™, with various additives and coatings, were launched to the ISS-NL on April 14, 2015 on the

  1. 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening.

    Science.gov (United States)

    Wenger, Tara L; Miller, Judith S; DePolo, Lauren M; de Marchena, Ashley B; Clements, Caitlin C; Emanuel, Beverly S; Zackai, Elaine H; McDonald-McGinn, Donna M; Schultz, Robert T

    2016-01-01

    Widespread use of microarray technology has led to increasing identification of 22q11.2 duplication syndrome (22q11.2DupS), the reciprocal syndrome of the well-characterized 22q11.2 deletion syndrome (22q11.2DS). Individuals with 22q11.2DS have elevated rates of community diagnoses of autism spectrum disorder (ASD), schizophrenia, and a range of medical problems and birth defects that necessitate extensive medical screening. Case reports of 22q11.2DupS include patients with ASD, fewer medical problems, and no schizophrenia; however, no prospective cohort study has been reported. The goals of the study were to (1) characterize the neuropsychiatric functioning of a cohort of individuals with 22q11.2DupS in comparison to large samples of typically developing controls (TDCs), ASD and 22q11.2DS; (2) estimate the prevalence of ASD in 22q11.2DupS; (3) determine whether the indications that prompted the genetic testing in 22q11.2DupS differ from 22q11.2DS and (4) determine whether comprehensive medical screening should be recommended for those diagnosed with 22q11.2DupS. Medical characterization was done by parental questionnaire and medical chart review of individuals with 22q11.2DupS (n = 37) and 22q11.2DS (n = 101). Neuropsychiatric characterization of children with 22.11.2DupS, 22q11.2DS, TDCs, and ASD was done by parent-report questionnaires; in addition, the ASD and 22q11.2DupS groups received the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Individuals with 22q11.2DupS, 22q11.2DS, and ASD had significantly impaired social interaction and adaptive behavior skills compared to TDCs. Overall, 38% of children aged 2-18 with 22q11.2DupS had community diagnoses of ASD, but fewer (14-25%) met on the basis of best clinical judgment that included ADI-R and ADOS data. Indications for genetic testing were significantly different for 22q11.2DupS and 22q11.2DS, with the deletions more commonly tested because of birth defects or medical problems

  2. Characterization of an L-arabinose isomerase from Bacillus coagulans NL01 and its application for D-tagatose production.

    Science.gov (United States)

    Mei, Wending; Wang, Lu; Zang, Ying; Zheng, Zhaojuan; Ouyang, Jia

    2016-06-30

    L-arabinose isomerase (AI) is a crucial catalyst for the biotransformation of D-galactose to D-tagatose. In previous reports, AIs from thermophilic bacterial strains had been wildly researched, but the browning reaction and by-products formed at high temperatures restricted their applications. By contrast, AIs from mesophilic Bacillus strains have some different features including lower optimal temperatures and lower requirements of metallic cofactors. These characters will be beneficial to the development of a more energy-efficient and safer production process. However, the relevant data about the kinetics and reaction properties of Bacillus AIs in D-tagatose production are still insufficient. Thus, in order to support further applications of these AIs, a comprehensive characterization of a Bacillus AI is needed. The coding gene (1422 bp) of Bacillus coagulans NL01 AI (BCAI) was cloned and overexpressed in the Escherichia coli BL21 (DE3) strain. The enzymatic property test showed that the optimal temperature and pH of BCAI were 60 °C and 7.5 respectively. The raw purified BCAI originally showed high activity in absence of outsourcing metallic ions and its thermostability did not change in a low concentration (0.5 mM) of Mn(2+) at temperatures from 70 °C to 90 °C. Besides these, the catalytic efficiencies (k cat/K m) for L-arabinose and D-galactose were 8.7 mM(-1) min(-1) and 1.0 mM(-1) min(-1) respectively. Under optimal conditions, the recombinant E. coli cell containing BCAI could convert 150 g L(-1) and 250 g L(-1) D-galactose to D-tagatose with attractive conversion rates of 32 % (32 h) and 27 % (48 h). In this study, a novel AI from B. coagulans NL01was cloned, purified and characterized. Compared with other reported AIs, this AI could retain high proportions of activity at a broader range of temperatures and was less dependent on metallic cofactors such as Mn(2+). Its substrate specificity was understood deeply by carrying out molecular

  3. Bouwstenen voor alarmberichten in het kader van NL-Alert : Rapportage over de ontwikkeling van berichtgeving voor burgeralarmering via cell broadcast

    NARCIS (Netherlands)

    Jagtman, H.M.; Sillem, S.; Ale, B.J.M.

    2011-01-01

    In dit rapport zijn de resultaten beschreven van de opdracht van het Ministerie van Veiligheid en Justitie aan de TU Delft om een aanzet te leveren tot een berichtendatabase ten behoeve van de implementatie van NL-Alert. In het kader van deze opdracht zijn opgesteld en onderzocht: • Een

  4. Reliability of the modified Paediatric Evaluation of Disability Inventory, Dutch version (PEDI-NL) for children with cerebral palsy and cerebral visual impairment.

    Science.gov (United States)

    Salavati, M; Waninge, A; Rameckers, E A A; de Blécourt, A C E; Krijnen, W P; Steenbergen, B; van der Schans, C P

    2015-02-01

    The aims of this study were to adapt the Paediatric Evaluation of Disability Inventory, Dutch version (PEDI-NL) for children with cerebral visual impairment (CVI) and cerebral palsy (CP) and determine test-retest and inter-respondent reliability. The Delphi method was used to gain consensus among twenty-one health experts familiar with CVI. Test-retest and inter-respondent reliability were assessed for parents and caregivers of 75 children (aged 50-144 months) with CP and CVI. The percentage identical scores of item scores were computed, as well as the interclass coefficients (ICC) and Cronbach's alphas of scale scores over the domains self-care, mobility, and social function. All experts agreed on the adaptation of the PEDI-NL for children with CVI. On item score, for the Functional Skills scale, mean percentage identical scores variations for test-retest reliability were 73-79 with Caregiver Assistance scale 73-81, and for inter-respondent reliability 21-76 with Caregiver Assistance scale 40-43. For all scales over all domains ICCs exceeded 0.87. For the domains self-care, mobility, and social function, the Functional Skills scale and the Caregiver Assistance scale have Cronbach's alpha above 0.88. The adapted PEDI-NL for children with CP and CVI is reliable and comparable to the original PEDI-NL. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Reliability of the modified Paediatric Evaluation of Disability Inventory, Dutch version (PEDI-NL) for children with cerebral palsy and cerebral visual impairment

    NARCIS (Netherlands)

    Salavati, M.; Waninge, A.; Rameckers, E. A. A.; de Blecourt, A. C. E.; Krijnen, W. P.; Steenbergen, B.; van der Schans, C. P.

    Purpose: The aims of this study were to adapt the Paediatric Evaluation of Disability Inventory, Dutch version (PEDI-NL) for children with cerebral visual impairment (CVI) and cerebral palsy (CP) and determine test-retest and inter-respondent reliability. Method: The Delphi method was used to gain

  6. An adenylyl cyclase like-9 gene (NlAC9 influences growth and fecundity in the brown planthopper, Nilaparvata lugens (Stål (Hemiptera: Delphacidae.

    Directory of Open Access Journals (Sweden)

    LinQuan Ge

    Full Text Available The cAMP/PKA intracellular signaling pathway is launched by adenylyl cyclase (AC conversion of adenosine triphosphate (ATP to 3', 5'-cyclic AMP (cAMP and cAMP-dependent activation of PKA. Although this pathway is very well known in insect physiology, there is little to no information on it in some very small pest insects, such as the brown planthopper (BPH, Nilaparvata lugens Stål. BPH is a destructive pest responsible for tremendous crop losses in rice cropping systems. We are investigating the potentials of novel pest management technologies from RNA interference perspective. Based on analysis of transcriptomic data, the BPH AC like-9 gene (NlAC9 was up-regulated in post-mating females, which led us to pose the hypothesis that NlAC9 is a target gene that would lead to reduced BPH fitness and populations. Targeting NlAC9 led to substantially decreased soluble ovarian protein content, yeast-like symbiont abundance, and vitellogenin gene expression, accompanied with stunted ovarian development and body size. Eggs laid were decreased and oviposition period shortened. Taken together, our findings indicated that NlAC9 exerted pronounced effects on female fecundity, growth and longevity, which strongly supports our hypothesis.

  7. An adenylyl cyclase like-9 gene (NlAC9) influences growth and fecundity in the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae).

    Science.gov (United States)

    Ge, LinQuan; Gu, HaoTian; Huang, Bo; Song, Qisheng; Stanley, David; Liu, Fang; Yang, Guo-Qing; Wu, Jin-Cai

    2017-01-01

    The cAMP/PKA intracellular signaling pathway is launched by adenylyl cyclase (AC) conversion of adenosine triphosphate (ATP) to 3', 5'-cyclic AMP (cAMP) and cAMP-dependent activation of PKA. Although this pathway is very well known in insect physiology, there is little to no information on it in some very small pest insects, such as the brown planthopper (BPH), Nilaparvata lugens Stål. BPH is a destructive pest responsible for tremendous crop losses in rice cropping systems. We are investigating the potentials of novel pest management technologies from RNA interference perspective. Based on analysis of transcriptomic data, the BPH AC like-9 gene (NlAC9) was up-regulated in post-mating females, which led us to pose the hypothesis that NlAC9 is a target gene that would lead to reduced BPH fitness and populations. Targeting NlAC9 led to substantially decreased soluble ovarian protein content, yeast-like symbiont abundance, and vitellogenin gene expression, accompanied with stunted ovarian development and body size. Eggs laid were decreased and oviposition period shortened. Taken together, our findings indicated that NlAC9 exerted pronounced effects on female fecundity, growth and longevity, which strongly supports our hypothesis.

  8. Mosaic 22q11.2 deletion and tetralogy of Fallot with absent pulmonary valve: an unreported association.

    Science.gov (United States)

    Prabhu, Sudesh; Jenny, Bryan; James, Harraway; Provenzano, Sylvio

    2015-04-01

    Chromosome 22q11.2 microdeletion is the most common microdeletion syndrome. Mosaic 22q11.2 deletions are very rare and only a few have been reported. We describe a case of a neonate with tetralogy of Fallot with absent pulmonary valve with mosaic 22q11.2 deletion. Fluorescent in situ hybridization analysis of lymphocytes showed a hemizygous 22q11.2 microdeletion in 66% of interphase nuclei. Microarray testing confirmed a 1.66 Mb deletion at 22q11.2. The child did not have any clinical manifestations of 22q11.2 deletion other than the cardiac malformation. © The Author(s) 2014.

  9. Degree of urbanization and mammographic density in Dutch breast cancer screening participants: results from the EPIC-NL cohort.

    Science.gov (United States)

    Emaus, Marleen J; Bakker, Marije F; Beelen, Rob M J; Veldhuis, Wouter B; Peeters, Petra H M; van Gils, Carla H

    2014-12-01

    It has been observed that women living in urban areas have a higher mammographic density (MD) compared to women living in rural areas. This association might be explained by regional differences in reproductive and lifestyle factors or perhaps by variation in exposure to ambient air pollution as air pollution particles have been described to show estrogenic activity. We investigated the association between degree of urbanization and MD, and aimed to unravel the underlying etiology. 2,543 EPIC-NL participants were studied, and general linear models were used. Urbanization was categorized into five categories according to the number of addresses/km(2). Information on reproductive and lifestyle factors was obtained from the recruitment questionnaire. Air pollution exposure was estimated using land-use regression models. MD was expressed as percent density (PD) and dense area (DA), and was quantified using Cumulus. Women living in extremely urbanized areas had a higher PD (21.4%, 95% confidence interval (CI) 20.5-22.3%) compared to women living in not urbanized areas (16.1, 95% CI 14.5-17.8%, P trend air pollution (adjusted PDextremely_urbanized = 22.1%, 95% CI 18.0-26.5% versus adjusted PDnot_urbanized = 16.9%, 95% CI 13.0-21.2, P trend urbanization is associated with MD. The association could not be explained by differences in reproductive and lifestyle factors or by variation in air pollution exposure.

  10. Effects of Inhibitors on the Transcriptional Profiling of Gluconobater oxydans NL71 Genes after Biooxidation of Xylose into Xylonate

    Directory of Open Access Journals (Sweden)

    Yong Xu

    2017-04-01

    Full Text Available D-Xylonic acid belongs to the top 30 biomass-based platform chemicals and represents a promising application of xylose. Until today, Gluconobacter oxydans NL71 is the most efficient microbe capable of fermenting xylose into xylonate. However, its growth is seriously inhibited when concentrated lignocellulosic hydrolysates are used as substrates due to the presence of various degraded compounds formed during biomass pretreatment. Three critical lignocellulosic inhibitors were thereby identified, i.e., formic acid, furfural, and 4-hydroxybenzaldehyde. As microbe fermentation is mostly regulated at the genome level, four groups of cell transcriptomes were obtained for a comparative investigation by RNA sequencing of a control sample with samples treated separately with the above-mentioned inhibitors. The digital gene expression profiles screened 572, 714 genes, and 408 DEGs was obtained by the comparisons among four transcriptomes. A number of genes related to the different functional groups showed characteristic expression patterns induced by three inhibitors, in which 19 genes were further tested and confirmed by qRT-PCR. We extrapolated many differentially expressed genes that could explain the cellular responses to the inhibitory effects. We provide results that enable the scientific community to better define the molecular processes involved in the microbes' responses to lignocellulosic inhibitors during the cellular biooxidation of xylose into xylonic acid.

  11. HowNutsAreTheDutch (HoeGekIsNL): A crowdsourcing study of mental symptoms and strengths.

    Science.gov (United States)

    Krieke, Lian Van Der; Jeronimus, Bertus F; Blaauw, Frank J; Wanders, Rob B K; Emerencia, Ando C; Schenk, Hendrika M; Vos, Stijn De; Snippe, Evelien; Wichers, Marieke; Wigman, Johanna T W; Bos, Elisabeth H; Wardenaar, Klaas J; Jonge, Peter De

    2016-06-01

    HowNutsAreTheDutch (Dutch: HoeGekIsNL) is a national crowdsourcing study designed to investigate multiple continuous mental health dimensions in a sample from the general population (n = 12,503). Its main objective is to create an empirically based representation of mental strengths and vulnerabilities, accounting for (i) dimensionality and heterogeneity, (ii) interactivity between symptoms and strengths, and (iii) intra-individual variability. To do so, HowNutsAreTheDutch (HND) makes use of an internet platform that allows participants to (a) compare themselves to other participants via cross-sectional questionnaires and (b) to monitor themselves three times a day for 30 days with an intensive longitudinal diary study via their smartphone. These data enable for personalized feedback to participants, a study of profiles of mental strengths and weaknesses, and zooming into the fine-grained level of dynamic relationships between variables over time. Measuring both psychiatric symptomatology and mental strengths and resources enables for an investigation of their interactions, which may underlie the wide variety of observed mental states in the population. The present paper describes the applied methods and technology, and presents the sample characteristics. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Roles of NlAKTIP in the Growth and Eclosion of the Rice Brown Planthopper, Nilaparvata lugens Stål, as Revealed by RNA Interference

    Directory of Open Access Journals (Sweden)

    Peiying Hao

    2015-09-01

    Full Text Available AKT-interacting protein (AKTIP interacts with serine/threonine protein kinase B (PKB/AKT. AKTIP modulates AKT’s activity by enhancing the phosphorylation of the regulatory site and plays a crucial role in multiple biological processes. In this study, the full length cDNA of NlAKTIP, a novel AKTIP gene in the brown planthopper (BPH Nilaparvata lugens, was cloned. The reverse transcription quantitive PCR (RT-qPCR results showed that the NlAKTIP gene was strongly expressed in gravid female adults, but was relatively weakly expressed in nymphs and male adult BPH. In female BPH, treatment with dsAKTIP resulted in the efficient silencing of NlAKTIP, leading to a significant reduction of mRNA levels, about 50% of those of the untreated control group at day 7 of the study. BPH fed with dsAKTIP had reduced growth with lower body weights and smaller sizes, and the body weight of BPH treated with dsAKTIP at day 7 decreased to about 30% of that of the untreated control. Treatment of dsAKTIP significantly delayed the eclosion for over 7 days relative to the control group and restricted ovarian development to Grade I (transparent stage, whereas the controls developed to Grade IV (matured stage. These results indicated that NlAKTIP is crucial to the growth and development of female BPH. This study provided a valuable clue of a potential target NlAKTIP for inhibiting the BPH, and also provided a new point of view on the interaction between BPH and resistant rice.

  13. Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Juyal, R.C.; Figuera, L.E.; Hauge, X. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1996-05-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable, multiple congenital anomalies/mental retardation syndrome caused by an interstitial deletion involving band p11.2 of chromosome 17. Toward the molecular definition of the interval defining this microdeletion syndrome, 62 unrelated SMS patients in conjunction with 70 available unaffected parents were molecularly analyzed with respect to the presence or absence of 14 loci in the proximal region of the short arm of chromosome 17. A multifaceted approach was used to determine deletion status at the various loci that combined (1) FISH analysis, (2) PCR and Southern analysis of somatic cell hybrids retaining the deleted chromosome 17 from selected patients, and (3) genotype determination of patients for whom a parent(s) was available at four microsatellite marker loci and at four loci with associated RFLPs. The relative order of two novel anonymous markers and a new microsatellite marker was determined in 17p11.2. The results confirmed that the proximal deletion breakpoint in the majority of SMS patients is located between markers D17S58 (EW301) and D17S446 (FG1) within the 17p11.1-17p11.2 region. The common distal breakpoint was mapped between markers cCI17-638, which lies distal to D17S71, and cCI17-498, which lies proximal to the Charcot Marie-Tooth disease type 1A locus. The locus D17S258 was found to be deleted in all 62 patients, and probes from this region can be used for diagnosis of the SMS deletion by FISH. Ten patients demonstrated molecularly distinct deletions; of these, two patients had smaller deletions and will enable the definition of the critical interval for SMS. 49 refs.

  14. Excitation of isomeric states 1h11/2 in (γ, n) reactions

    International Nuclear Information System (INIS)

    Tonchev, A.P.; Gangrskij, Yu.P.; Belov, A.G.

    1995-01-01

    The cross sections of (γ, n) reactions were measured for ground and isomeric states 1h 11/2 in 16 isotopes of Pd, Cd, Sn, Te, Ba, Ce, Nd and Sm. The energy of γ-rays was placed in the region of Giant Dipole Resonance. An activation method of measurements has been used. IR dependence of neutron and proton number in nucleus was detected and of excitation energy of residual nucleus as well. Different factors influencing the values of the isomeric ratios are discussed. 20 refs., 5 figs., 2 tabs

  15. Critical region within 22q11.2 linked to higher rate of autism spectrum disorder.

    Science.gov (United States)

    Clements, Caitlin C; Wenger, Tara L; Zoltowski, Alisa R; Bertollo, Jennifer R; Miller, Judith S; de Marchena, Ashley B; Mitteer, Lauren M; Carey, John C; Yerys, Benjamin E; Zackai, Elaine H; Emanuel, Beverly S; McDonald-McGinn, Donna M; Schultz, Robert T

    2017-01-01

    Previous studies have reported no clear critical region for medical comorbidities in children with deletions or duplications of 22q11.2. The purpose of this study was to evaluate whether individuals with small nested deletions or duplications of the LCR-A to B region of 22q11.2 show an elevated rate of autism spectrum disorder (ASD) compared to individuals with deletions or duplications that do not include this region. We recruited 46 patients with nested deletions ( n  = 33) or duplications ( n  = 13) of 22q11.2, including LCR-A to B ( n del  = 11), LCR-A to C ( n del  = 4), LCR-B to D ( n del  = 14; n dup  = 8), LCR-C to D ( n del  = 4; n dup  = 2), and smaller nested regions ( n  = 3). Parent questionnaire, record review, and, for a subset, in-person evaluation were used for ASD diagnostic classification. Rates of ASD in individuals with involvement of LCR-B to LCR-D were compared with Fisher's exact test to LCR-A to LCR-B for deletions, and to a previously published sample of LCR-A to LCR-D for duplications. The rates of medical comorbidities and psychiatric diagnoses were determined from questionnaires and chart review. We also report group mean differences on psychiatric questionnaires. Individuals with deletions involving LCR-A to B showed a 39-44% rate of ASD compared to 0% in individuals whose deletions did not involve LCR-A to B. We observed similar rates of medical comorbidities in individuals with involvement of LCR-A to B and LCR-B to D for both duplications and deletions, consistent with prior studies. Children with nested deletions of 22q11.2 may be at greater risk for autism spectrum disorder if the region includes LCR-A to LCR-B. Replication is needed.

  16. Common variant at 16p11.2 conferring risk of psychosis

    DEFF Research Database (Denmark)

    Steinberg, S; de Jong, S; Mattheisen, M

    2014-01-01

    -wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel...... variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index...

  17. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies

    DEFF Research Database (Denmark)

    de Kovel, Carolien G F; Trucks, Holger; Helbig, Ingo

    2010-01-01

    at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic risk factor for common idiopathic generalized epilepsy...... syndromes, implicating that other recurrent microdeletions may also be involved in epileptogenesis. This study aimed to investigate the impact of five microdeletions at the genomic hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic risk to common idiopathic generalized epilepsy...... 10(-7)). Microdeletions were observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2 (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and 22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the microdeletions at 15q11...

  18. Characteristics of 22q 11.2 deletion syndrome undiagnosed until adulthood: an example suggesting the importance of psychiatric manifestations

    OpenAIRE

    Furuya, Kenta; Sasaki, Yosuke; Takeuchi, Taizo; Urita, Yoshihisa

    2015-01-01

    Patients with chromosome 22q11.2 deletion syndrome (22q11.2DS) exhibit various combinations of signs and symptoms including facial dysmorphism, thymus absence, hypoparathyroidism, cellular immunodeficiency and cardiac abnormalities caused by microdeletion of chromosome 22q11.2. Most cases are diagnosed during post-natal cardiac evaluation, though some are diagnosed at later stages. We report the case of a 39-year-old man with 22q11.2DS presenting with seizure due to tardily manifested hypocal...

  19. NL Kids online

    NARCIS (Netherlands)

    Jos de Haan

    2010-01-01

    In Nederland, maar ook elders, verkennen jongeren intensief de mogelijkheden van internet. Deze verkenning begint overal op steeds jongere leeftijd. Jongeren krijgen te maken met zowel de positieve als de negatieve kanten van internet. Dit rapport bestudeert de aangeboden kansen en risico's van

  20. Differences in speech and language abilities between children with 22q11.2 deletion syndrome and children with phenotypic features of 22q11.2 deletion syndrome but without microdeletion.

    Science.gov (United States)

    Rakonjac, Marijana; Cuturilo, Goran; Stevanovic, Milena; Jelicic, Ljiljana; Subotic, Misko; Jovanovic, Ida; Drakulic, Danijela

    2016-08-01

    22q11.2DS is the most common microdeletion syndrome in humans, usually associated with speech and language delay (SLD). Approximately 75% of children with 22q11.2 microdeletion have congenital heart malformations (CHM) which after infant open-heart surgery might lead to SLD. The purpose of this study was to determine whether factors associated with microdeletion contribute to SLD in children with 22q11.2DS. We compared speech and language abilities of two groups of school-aged children: those with 22q11.2 microdeletion (E1) and those with the phenotype resembling 22q11.2DS but without the microdeletion (E2). An age-matched group of typically developing children was also tested. The obtained results revealed that children from group E1 have lower level of speech and language abilities compared to children from group E2 and control group. Additionally, mild to moderate SLD was detected in children from group E2 compared to children from the control group. The obtained results imply that both CHM after infant open-heart surgery and other factors associated with 22q11.2 microdeletion, contribute to SLD in patients with 22q11.2 microdeletion. Based on this, we could postulate that there is/are some potential candidate gene(s), located in the 22q11.2 region, whose function could be important for speech and language development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The immune deficiency of chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Morsheimer, Megan; Brown Whitehorn, Terri F; Heimall, Jennifer; Sullivan, Kathleen E

    2017-09-01

    The syndrome originally described by Dr. Angelo DiGeorge had immunodeficiency as a central component. When a 22q11.2 deletion was identified as the cause in the majority of patients with DiGeorge syndrome, the clinical features of 22q11.2 deletion syndrome became so expansive that the immunodeficiency became less prominent in our thinking about the syndrome. This review will focus on the immune system and the changes in our understanding over the past 50 years. Initially characterized as a pure defect in T cell development, we now appreciate that many of the clinical features related to the immunodeficiency are well downstream of the limitation imposed by a small thymus. Dysfunctional B cells presumed to be secondary to compromised T cell help, issues related to T cell exhaustion, and high rates of atopy and autoimmunity are aspects of management that require consideration for optimal clinical care and for designing a cogent monitoring approach. New data on atopy are presented to further demonstrate the association. © 2017 Wiley Periodicals, Inc.

  2. B cell development in chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Derfalvi, Beata; Maurer, Kelly; McDonald McGinn, Donna M; Zackai, Elaine; Meng, Wenzhao; Luning Prak, Eline T; Sullivan, Kathleen E

    2016-02-01

    Chromosome 22q11.2 deletion syndrome is a common immune deficiency associated with thymic hypoplasia. Most patients did not survive until the mid-1980s and now there is a growing adult population. B cell and immunoglobulin defects have been described and appear to be increased in the adult population. We used flow cytometry, B cell stimulation and repertoire analysis to understand B cell function. B cell production at early stages appeared to be normal in patients but adult patients exhibited a deficit of switched memory B cells. Follicular helper T cells were present at higher percentages in patients and they exhibited a more activated phenotype in patients compared to controls. In spite of that, somatic hypermutation was decreased in patients compared to controls at all ages. Fewer mutations per clone were seen, strongly implicating aberrant T cell help. Therefore, patients with chromosome 22q11.2 deletion syndrome have a progressive decrease in switched memory B cells and evidence of compromised T cell help. In children, evidence of compromised T cell help is limited to decreased somatic hypermutation. With age, greater manifestations become apparent even though a minority of patients have hypogammaglobulinemia. As this population ages, this has important implications for management. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A patient with a de novo distal 22q11.2 microdeletion and anxiety disorder.

    Science.gov (United States)

    Verhoeven, Willem; Egger, Jos; Brunner, Han; de Leeuw, Nicole

    2011-02-01

    We report on a young female with normal intelligence evaluated for long-term anxiety. Her history includes prematurity, neonatal feeding problems, surgical correction of congenital heart defects, recurrent upper airway and urinary tract infections, and delayed motor and developmental milestones. Physical examination disclosed small stature and minor dysmorphisms. Chromosome analysis, 22q11.2 FISH analysis, and subtelomeric MLPA testing did not detect any abnormalities. Genome wide SNP Array analysis showed a de novo deletion in 22q11.21q11.22, the so-called distal 22q11 microdeletion that involves the MAPK1 gene. A diagnosis of panic disorder was made and the patient was successfully treated with a daily dose of 20 mg citalopram. To our knowledge, this is the first adolescent patient with a long history of complaints about anxiety and a distal 22q11 microdeletion. We speculate that genes from the deleted region, especially MAPK1, increase the neurobiological susceptibility to anxiety disorders that may be a part of the psychopathological phenotype of the distal 22q11.2 microdeletion syndrome. Copyright © 2010 Wiley-Liss, Inc.

  4. C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome.

    Science.gov (United States)

    Konen, Osnat; Armstrong, Derek; Clarke, Howard; Padfield, Nancy; Weksberg, Rosanna; Blaser, Susan

    2008-07-01

    Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS.

  5. C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan [Hospital for Sick Children, Diagnostic Imaging, Toronto (Canada); Clarke, Howard [Hospital for Sick Children, Plastic Surgery, Toronto (Canada); Weksberg, Rosanna [Hospital for Sick Children, Clinical and Metabolic Genetics, Toronto (Canada)

    2008-07-15

    Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

  6. C1-2 vertebral anomalies in 22q11.2 microdeletion syndrome

    International Nuclear Information System (INIS)

    Konen, Osnat; Armstrong, Derek; Padfield, Nancy; Blaser, Susan; Clarke, Howard; Weksberg, Rosanna

    2008-01-01

    Chromosome 22q11.2 microdeletion syndrome (22q11DS) is characterized by cleft palate, cardiac anomalies, characteristic facies, high prevalence of skeletal anomalies and learning disability. To evaluate the prevalence of craniovertebral junction anomalies in children with 22q11DS and compare these findings to those in nonsyndromic children with velopharyngeal insufficiency (VPI). Sequential CT scans performed for presurgical carotid assessment in 76 children (45 children positive for chromosome 22q11.2 deletion and 31 negative for the deletion) with VPI were retrospectively evaluated for assessment of C1-2 anomalies. C1-2 vertebral anomalies, specifically midline C1 defects, uptilted or upswept posterior elements of C2 and fusions of C2-3, were nearly universal in our cohort of 22q11DS patients with VPI. They were strikingly absent in the majority of non-22q11DS patients with VPI. C1-2 vertebral anomalies, particularly those listed above, are important radiographic markers for 22q11DS. (orig.)

  7. Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland

    Directory of Open Access Journals (Sweden)

    Zeyland Joanna

    2010-12-01

    Full Text Available Abstract Background The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted children's parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients. Methods The analysis of microdeletions was conducted using fluorescence in situ hybridization (FISH on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple specific to the HIRA (TUPLE1, DGCR1 region at 22q11 was used for the hybridisation. Results Microdeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group. Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25% without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated de novo. Conclusions Patients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics

  8. Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland.

    Science.gov (United States)

    Wozniak, Anna; Wolnik-Brzozowska, Danuta; Wisniewska, Marzena; Glazar, Renata; Materna-Kiryluk, Anna; Moszura, Tomasz; Badura-Stronka, Magdalena; Skolozdrzy, Joanna; Krawczynski, Maciej R; Zeyland, Joanna; Bobkowski, Waldemar; Slomski, Ryszard; Latos-Bielenska, Anna; Siwinska, Aldona

    2010-12-06

    The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal) coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted children's parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients. The analysis of microdeletions was conducted using fluorescence in situ hybridization (FISH) on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple) specific to the HIRA (TUPLE1, DGCR1) region at 22q11 was used for the hybridisation. Microdeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group). Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25%) without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated de novo. Patients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics, ranging from discreet to quite strong. The deletion was inherited

  9. Effects of Long-Term Developmental Patterns of Adiposity on Levels of C-Reactive Protein and Fibrinogen among North-American Men and Women: The Spokane Heart Study

    Directory of Open Access Journals (Sweden)

    Trynke Hoekstra

    2014-06-01

    Full Text Available This study examined the heterogeneity in BMI development by identifying distinct developmental trajectories. These trajectories were further investigated by relating them to markers of low-grade inflammation later in life. Data from approximately 400 healthy volunteers participating in the Spokane Heart Study were collected in 2-year intervals, and four waves of data were available for the current analyses. Body weight was measured by BMI and low-grade inflammation by high-sensitivity C-reactive protein (CRP and fibrinogen. Up to date statistical techniques, i.e. latent class growth models, were used to analyse heterogeneity in body weight, and linear regressions were run to analyse possible associations between trajectories of body weight and CRP/fibrinogen levels. Six trajectories were identified (three stable, two increasing, and one decreasing which differed significantly on CRP/fibrinogen levels, highlighting the importance of weight trajectories. The differences were only partly explained by variations in lifestyle habits.

  10. Selected trace-element and synthetic-organic compound data for streambed sediment from the Clark Fork-Pend Oreille and Spokane River basins, Montana, Idaho, and Washington, 1998

    Science.gov (United States)

    Beckwith, Michael A.

    2002-01-01

    Streambed-sediment samples were collected at 22 sites during the summer of 1998 as part of the U.S. Geological Survey National Water-Quality Assessment Program. Sampling sites in the Clark Fork-Pend Oreille and Spokane River basins represented a wide range of environmental conditions including pristine mountain streams and large rivers affected by mining-related and urban activities. Samples were analyzed for 45 inorganic major and trace elements, 109 syn­thetic organic compounds, and carbon. This report pre­sents the selected results of streambed-sediment sampling from the Clark Fork-Pend Oreille and Spo­kane River basins in Montana, Idaho, and Washington.

  11. Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes

    NARCIS (Netherlands)

    Delio, Maria; Guo, Tingwei; McDonald-McGinn, Donna M.; Zackai, Elaine; Herman, Sean; Kaminetzky, Mark; Higgins, Anne Marie; Coleman, Karlene; Chow, Carolyn; Jarlbrzkowski, Maria; Bearden, Carrie E.; Bailey, Alice; Vangkilde, Anders; Olsen, Line; Olesen, Charlotte; Skovby, Flemming; Werge, Thomas M.; Templin, Ludivine; Busa, Tiffany; Philip, Nicole; Swillen, Ann; Vermeesch, Joris R.; Devriendt, Koen; Schneider, Maude; Dahoun, Sophie; Eliez, Stephan; Schoch, Kelly; Hooper, Stephen R.; Shashi, Vandana; Samanich, Joy; Marion, Robert; van Amelsvoort, Therese; Boot, Erik; Klaassen, Petra; Duijff, Sasja N.; Vorstman, Jacob; Yuen, Tracy; Silversides, Candice; Chow, Eva; Bassett, Anne; Frisch, Amos; Weizman, Abraham; Gothelf, Doron; Niarchou, Maria; van den Bree, Marianne; Owen, Michael J.; Suñer, Damian Heine; Andreo, Jordi Rosell; Armando, Marco; Vicari, Stefano; Digilio, Maria Cristina; Auton, Adam; Kates, Wendy R.; Wang, Tao; Shprintzen, Robert J.; Emanuel, Beverly S.; Morrow, Bernice E.

    2013-01-01

    Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications.

  12. Comparing the Broad Socio-Cognitive Profile of Youth with Williams Syndrome and 22Q11.2 Deletion Syndrome

    Science.gov (United States)

    Weisman, O.; Feldman, R.; Burg-Malki, M.; Keren, M.; Geva, R.; Diesendruck, G.; Gothelf, D.

    2017-01-01

    Background: Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. Methods: Eighty-two children participated…

  13. Examining a New Method to Studying Velopharyngeal Structures in a Child with 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Kollara, Lakshmi; Schenck, Graham; Jaskolka, Michael; Perry, Jamie L.

    2017-01-01

    Purpose: To date, no studies have imaged the velopharynx in children with 22q11.2 deletion syndrome (22q11.2 DS) without the use of sedation. Dysmorphology in velopharyngeal structures has been shown to have significant negative implications on speech among these individuals. This single case study was designed to assess the feasibility of a…

  14. Working Memory Impairments in Chromosome 22q11.2 Deletion Syndrome: The Roles of Anxiety and Stress Physiology

    Science.gov (United States)

    Sanders, Ashley F.; Hobbs, Diana A.; Stephenson, David D.; Laird, Robert D.; Beaton, Elliott A.

    2017-01-01

    Stress and anxiety have a negative impact on working memory systems by competing for executive resources and attention. Broad memory deficits, anxiety, and elevated stress have been reported in individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS). We investigated anxiety and physiological stress reactivity in relation to visuospatial…

  15. Does Differential Visual Exploration Contribute to Visual Memory Impairments in 22Q11.2 Microdeletion Syndrome?

    Science.gov (United States)

    Bostelmann, M.; Glaser, B.; Zaharia, A.; Eliez, S.; Schneider, M.

    2017-01-01

    Background: Chromosome 22q11.2 microdeletion syndrome (22q11.2DS) is a genetic syndrome characterised by a unique cognitive profile. Individuals with the syndrome present several non-verbal deficits, including visual memory impairments and atypical exploration of visual information. In this study, we seek to understand how visual attention may…

  16. Influence of chromosome 22q11.2 microdeletion on postoperative calcium level after cardiac-correction surgery.

    Science.gov (United States)

    Shen, Li; Gu, Haitao; Wang, Dongjing; Yang, Chi; Xu, Zhengfeng; Jing, Hua; Jiang, Yongzhong; Ding, Yibing; Hou, Huacheng; Ge, Zhijuan; Chen, Shilin; Mo, Xuming; Yi, Long

    2011-10-01

    One of the most common constitutional chromosomal abnormalities, 22q11.2 microdeletion (del22q11.2) syndrome has diverse medical complications, such as congenital heart defect, hypocalcaemia, and immune deficiency, which require coordinated multidisciplinary care. Until now, the natural history of hypocalcaemia in chromosome del22q11.2 syndrome had been only partly documented, but there has been limited recognition of the importance of calcium status during the postoperative period when altered calcium status may be associated with serious complications. The goals of our study were (1) to delineate the clinical characteristics of serum calcium in patients with del22q11.2 during the postoperative period and (2) to make recommendations for the investigation and management of del22q11.2 patients after cardiac correction. This study included 22 children diagnosed with del22q11.2 syndrome and 110 children without del22q11.2 syndrome from Nanjing Children's Hospital. Clinical examinations and blood ionized calcium testing were reviewed retrospectively. A comparative study of postoperative calcium levels and complications of del22q11.2 patients with nondeletion patients was performed. Association between postoperative hypocalcaemia and adverse incidents after cardiac correction was also examined. Postoperative hypocalcaemia was observed among 86.4% of del22q11.2 patients and among only 47.3% of nondeletion subjects. The difference was statistically significant (P = 0.0017). Patients with del22q11.2 syndrome also had a much sharper decrease in serum calcium levels during the first 6 h after surgery than nondeletion patients. Postoperative clinical analysis showed that del22q11.2 patients with hypocalcaemia experience more postoperative complications (18 of 19) and greater mortality (5 of 19) after cardiac correction than del22q11.2 patients without normal calcium levels and nondeletion patients. Del22q11.2 children have high susceptibility of hypocalcaemia during the

  17. 22q11.2 Deletion Syndrome Is Associated With Impaired Auditory Steady-State Gamma Response

    DEFF Research Database (Denmark)

    Larsen, Kit Melissa; Pellegrino, Giovanni; Birknow, Michelle Rosgaard

    2017-01-01

    The 22q11.2 deletion syndrome confers a markedly increased risk for schizophrenia. 22q11.2 deletion carriers without manifest psychotic disorder offer the possibility to identify functional abnormalities that precede clinical onset. Since schizophrenia is associated with a reduced cortical gamma...... response to auditory stimulation at 40 Hz, we hypothesized that the 40 Hz auditory steady-state response (ASSR) may be attenuated in nonpsychotic individuals with a 22q11.2 deletion. Eighteen young nonpsychotic 22q11.2 deletion carriers and a control group of 27 noncarriers with comparable age range (12...... Hz click stimulation. Both gamma power and inter-trial phase coherence of the ASSR were markedly reduced in the 22q11.2 deletion group. The ability to phase lock cortical gamma activity to regular auditory 40 Hz stimulation correlated with the individual expression of negative symptoms in deletion...

  18. An interictal schizophrenia-like psychosis in an adult patient with 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Yasutaka Tastuzawa

    2015-01-01

    Full Text Available In addition to causing polymalformative syndrome, 22q11.2 deletion can lead to various neuropsychiatric disorders including mental retardation, psychosis, and epilepsy. However, few reports regarding epilepsy-related psychosis in 22q11.2 deletion syndrome (22q11.2DS exist. We describe the clinical characteristics and course of 22q11.2DS in a Japanese patient with comorbid mild mental retardation, childhood-onset localization-related epilepsy, and adult-onset, interictal schizophrenia-like psychosis. From a diagnostic viewpoint, early detection of impaired intellectual functioning and hyperprolinemia in patients with epilepsy with 22q11.2DS may be helpful in predicting the developmental timing of interictal psychosis. From a therapeutic viewpoint, special attention needs to be paid to phenytoin-induced hypocalcemia in this syndrome.

  19. Prevalence and clinical manifestations of 22q11.2 microdeletion in adults with selected conotruncal anomalies.

    Science.gov (United States)

    Beauchesne, Luc M; Warnes, Carole A; Connolly, Heidi M; Ammash, Naser M; Grogan, Martha; Jalal, Syed M; Michels, Virginia V

    2005-02-15

    This study was designed to determine the prevalence and clinical manifestations of 22q11.2 microdeletion in adults with selected conotruncal anomalies and to assess the clinician's ability to predict the presence or absence of 22q11.2 microdeletion on the basis of clinical features. It is known that 22q11.2 microdeletion is a chromosomal anomaly with cardiac and extracardiac manifestations. The prevalence and manifestations in adults have not been well characterized. A total of 103 consecutive adults with either tetralogy of Fallot (TOF), pulmonary atresia/ventricular septal defect (PA/VSD), or truncus arteriosus (TA) were prospectively screened for 22q11.2 microdeletion using a fluorescence in situ hybridization (FISH) assay. Clinicians were asked to predict 22q11.2 microdeletion status on the basis of clinical features. A geneticist blinded to FISH assay results reviewed photographs of the patients for typical dysmorphic features of 22q11.2 microdeletion. Six patients (prevalence 5.8%, 95% confidence interval 1.3 to 10.3) had 22q11.2 microdeletion (3 with TOF, 2 with PA/VSD, 1 with TA). In two of these patients, the clinician incorrectly predicted absence of the deletion. In three, typical dysmorphic features of 22q11.2 microdeletion were absent. Our work showed that 22q11.2 microdeletion is under-recognized in adults with congenital heart disease. The absence of typical phenotypic features makes it difficult to correctly predict if the deletion is present. Screening for 22q11.2 microdeletion should be considered in adults with high-risk cardiac lesions, as it has important implications in reproductive counseling and surveillance for associated extracardiac manifestations.

  20. Subthreshold social cognitive deficits may be a key to distinguish 22q11.2DS from schizophrenia.

    Science.gov (United States)

    Peyroux, Elodie; Rigard, Caroline; Saucourt, Guillaume; Poisson, Alice; Plasse, Julien; Franck, Nicolas; Demily, Caroline

    2018-03-25

    Social cognitive impairments are core features in 22q11.2 deletion syndrome (22q11.2DS) and schizophrenia (SCZ). Indeed, adults with 22q.11.2 DS often have poorer social competence as well as poorer performance on measures of social cognitive skills (emotion recognition and theory of mind, ToM) compared with typically developing people. However, studies comparing specific social cognitive components in 22q11.2DS and SCZ have not yet been widely conducted. In this study we compared performances of 22q11.2DS and SCZ on both facial emotion recognition and ToM. Patients with 22q11.2DS (n = 18) and matched SCZ patients were recruited. After neuropsychological testing, the facial emotion recognition test assessed the patients' ability to recognize six basic, universal emotions (joy, anger, sadness, fear, disgust, and contempt). The Versailles-situational intentional reading evaluated ToM with six scenes from movies showing characters in complex interactions (involving hints, lies, and indirect speech). We show that 22q11.2DS exhibited significantly lower performance in emotion recognition than SCZ patients did, especially for disgust, contempt, and fear. This impairment seems to be a core cognitive phenotype in 22q11.2DS, regardless of the presence of SCZ symptoms. Concerning ToM, our results may highlight the same impairment level in 22q11.2DS and SCZ but require to be replicated in a larger cohort. Our results document the existence of threshold social cognitive deficits distinguishing 22q11.2DS from SCZ. © 2018 John Wiley & Sons Australia, Ltd.

  1. Paroxysmal Kinesigenic Dyskinesia Caused by 16p11.2 Microdeletion

    Directory of Open Access Journals (Sweden)

    Pichet Termsarasab

    2014-11-01

    Full Text Available Background: Four cases of paroxysmal kinesigenic dyskinesia (PKD have been reported in individuals with proximal 16p11.2 microdeletions that include PRRT2. Case Report: We describe a fifth patient with PKD, features of Asperger’s syndrome, and mild language delays. Sanger sequencing of the PRRT2 gene did not identify any mutations implicated in PKD. However, microarray‐based comparative genomic hybridization (aCGH detected a 533.9‐kb deletion on chromosome 16, encompassing over 20 genes and transcripts. Discussion: This case underscores the importance of aCGH testing for individuals with PKD who do not have PRRT2 mutations, particularly when developmental delays, speech problems, intellectual disability, and/or autism spectrum disorder are present.

  2. Xp 11.2 translocation renal carcinoma in young adults; recently classified distinct subtype

    International Nuclear Information System (INIS)

    Kmetec, Andrej; Jeruc, Jera

    2014-01-01

    XP11.2 renal translocation carcinomas are often encountered in paediatric group of patients where they are believed to be rather indolent. They are rare but more aggressive in young adults. They are slow growing, sometimes without characteristic symptoms and their biologic behaviour is uncertain. We report two cases of this type of tumour in Slovenian young adult males with long and unusual history. Tumours were confirmed imunohistologically by positive reaction for CD10, P504S and TFE3. According to the indications in the literature prognosis of these tumours in young adults depends upon the stage. It seems that cysts, haematomas and necrosis around the kidney are often encountered in these tumours. In advanced stage with lymph nodes involvement or distant metastases, the prognosis is poor. Surgery seems to be basic mode of therapy

  3. The tyrosinase-positive oculocutaneous albinism locus maps to chromosome 15q11. 2-q12

    Energy Technology Data Exchange (ETDEWEB)

    Ramsay, M.; Colman, M.A.; Stevens, G.; Zwane, E.; Kromberg, J.; Jenkins, T. (South African Institute for Medical Research, Johannesburg (South Africa)); Garral, M.

    1992-10-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA), an autosomal recessive disorder of the melanin biosynthetic pathway, is the most common type of albinism occurring worldwide. In southern African Bantu-speaking negroids it has an overall prevalence of about 1/3,900. Since the basic biochemical defect is unknown, a linkage study with candidate loci, candidate chromosomal regions, and random loci was undertaken. The ty-pos OCA locus was found to be linked to two arbitrary loci, D15S10 and D15S13, in the Prader-Willi/Angelman chromosomal region on chromosome 15q11.2-q12. The pink-eyed dilute locus, p, on mouse chromosome 7, maps close to a region of homology on human chromosome 15q, and we postulate that the ty-pos OCA and p loci are homologous. 43 refs., 2 figs., 1 tab.

  4. Failure to thrive as presentation in a patient with 22q11.2 microdeletion.

    Science.gov (United States)

    Bossi, Grazia; Gertosio, Chiara; Meazza, Cristina; Farello, Giovanni; Bozzola, Mauro

    2016-02-11

    Abnormalities of chromosome 22q11, including deletions and translocations, have been described in association with different birth defects and malformations occurring in many combinations and degrees of severity. We describe the case of an 8 month-old infant with no dysmorphic signs who showed progressive postnatal growth failure and no chronic systemic diseases. We found a 22q11.2 microdeletion, inherited from the mother, suggesting the diagnosis of DiGeorge syndrome. The patient had an isolated growth hormone (GH) deficiency and a significant increase in linear growth during the first and the second year of GH therapy, and a recovery of weight was shown. Sometimes, in infants with growth failure a genetic analysis is strongly suggested, since chromosomal abnormalities may be present.

  5. The Creatine Transporter Gene Paralogous at 16p11.2 Is Expressed in Human Brain

    Directory of Open Access Journals (Sweden)

    Nadia Bayou

    2008-01-01

    We report on the clinical, cytogenetic, and molecular findings in a boy with autism carrying a de novo translocation t(7;16(p22.1;p11.2. The chromosome 16 breakpoint disrupts the paralogous SLC6A8 gene also called SLC6A10 or CT2. Predicted translation of exons and RT-PCR analysis reveal specific expression of the creatine transporter paralogous in testis and brain. Several studies reported on the role of X-linked creatine transporter mutations in individuals with mental retardation, with or without autism. The existence of disruption in SLC6A8 paralogous gene associated with idiopathic autism suggests that this gene may be involved in the autistic phenotype in our patient.

  6. Completion Report for Model Evaluation Well ER-11-2: Corrective Action Unit 98: Frenchman Flat

    Energy Technology Data Exchange (ETDEWEB)

    NSTec Underground Test Area and Boreholes Programs and Operations

    2013-01-22

    Model Evaluation Well ER-11-2 was drilled for the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office in support of Nevada Environmental Management Operations at the Nevada National Security Site (formerly known as the Nevada Test Site). The well was drilled in August 2012 as part of a model evaluation program in the Frenchman Flat area of Nye County, Nevada. The primary purpose of the well was to provide detailed geologic, hydrogeologic, chemical, and radionuclide data that can be used to test and build confidence in the applicability of the Frenchman Flat Corrective Action Unit flow and transport models for their intended purpose. In particular, this well was designed to provide data to evaluate the uncertainty in model forecasts of contaminant migration from the upgradient underground nuclear test PIN STRIPE, conducted in borehole U-11b in 1966. Well ER-11-2 will provide information that can be used to refine the Phase II Frenchman Flat hydrostratigraphic framework model if necessary, as well as to support future groundwater flow and transport modeling. The main 31.1-centimeter (cm) hole was drilled to a total depth of 399.6 meters (m). A completion casing string was not set in Well ER-11-2. However, a piezometer string was installed in the 31.1-cm open hole. The piezometer is composed of 7.3-cm stainless-steel tubing hung on 6.0-cm carbon-steel tubing via a crossover sub. The piezometer string was landed at 394.5 m, for monitoring the lower tuff confining unit. Data collected during and shortly after hole construction include composite drill cuttings samples collected every 3.0 m, various geophysical logs, water quality (including tritium and other test-related radionuclides) measurements, and water level measurements. The well penetrated 42.7 m of Quaternary and Tertiary alluvium and 356.9 m of Tertiary volcanic rock. The water-level measured in the piezometer string on September 25, 2012, was 353.8 m below ground surface. No

  7. Response of Organic Materials to Hypervelocity Impacts (up to 11.2 km/sec)

    Science.gov (United States)

    Bass, D. S.; Murphy, W. M.; Miller, G. P.; Grosch, D. J.; Walker, J. D.; Mullin, A.; Waite, J. H.

    1998-09-01

    It is speculated that organic-rich planetesimals played a role in the origin of life on Earth. However, the mechanism by which organics could have been delivered from space to a planetary surface is difficult to determine. Particularly problematic is the question of the stability of organic material under hypervelocity impact conditions. Although some evidence suggests organic molecules cannot survive impacts from projectile velocities greater than about 10 km/sec [1], other investigators have found that impacts create a favorable environment for post-shock recombination of organic molecules in the plume phase [2, 3]. Understanding the mechanisms involved in delivering organics to a planetary surface remains difficult to assess due to the lack of experimental results of hypervelocity impacts, particularly in the velocity range of tens of km/sec. Organic material preservation and destruction from impact shocks, the synthesis of organics in the post-impact plume environment, and implications of these processes for Earth and Mars can be investigated by launching an inorganic projectile into an analog planetesimal-and-bolide organic-rich target. We explored the pressure and temperature ranges of hypervelocity impacts (11.2 km/sec) through simulations with CTH impact physics computer code. Using an inhibited shaped-charge launcher, we also experimentally determined the response of organic material to hypervelocity impacts. Initial work focused on saturating well-characterized zeolitic tuff with an aqueous solution containing dissolved naphthalene, a common polycyclic aromatic hydrocarbon (PAH). Porosity measurements, thin section, and x-ray diffraction analyses were performed to determine that the tuff is primarily fine-grained clinoptilolite. In order to distinguish between contaminants and compounds generated or destroyed in the impact, we tagged the aqueous component of our target with deuterium. Experimental tests revealed that to first order, naphthalene survived

  8. Detection of the deletion on Yp11.2 in a Chinese population.

    Science.gov (United States)

    Chen, Wenjing; Wu, Weiwei; Cheng, Jianding; Zhang, Yinming; Chen, Yong; Sun, Hongyu

    2014-01-01

    Sex determination tests based on Amelogenin gene as part of commercial PCR multiplex reaction kits have been widely applied in forensic DNA analysis. Mutations that cause dropout of Y chromosomal Amelogenin gene (AMELY) could lead to errors in gender determination and mixture interpretation. To infer the mechanism and estimate the dropout frequency of AMELY and adjacent Y-STRs, we studied 3 samples with AMELY dropout combined with DYS458 and/or DYS456 and 37 samples with DYS456 dropout. DYS456, DYS458 and AMELY are located in the Yp11.2 region. The singleplex amplification system showed the null alleles could be caused by fragment deletion in Yp11.2 rather than a point mutation in the primer binding region. After detection of the 17 Y-STR and 77 STS markers, the deletion map showed different patterns. The DYS456-AMELY-DYS458 deletion pattern was the largest, breaking from 3.60 Mb to 8.29 Mb in the Y chromosome, and the overall frequency was 0.0077%. The AMELY-DYS458 deletion pattern was broke from 6.74 Mb to 9.17 Mb, with a 0.0155% frequency. The DYS456 negative pattern was concentrated in two main deletion regions, with a 0.8220% frequency. The frequency of all negative pattern was 0.0155%. All the AMELY-DYS458 and DYS456-AMELY-DYS458, and 92% of the DYS456 deletion patterns belonged to Hg O3, the rest belonged to Hg Q. The DYS456 deletion pattern was first reported in Chinese population. The current and previous findings suggest additional gender test for ambiguous sex determination may be required. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Generalized Epilepsy and Myoclonic Seizures in 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Strehlow, Vincent; Swinkels, Marielle E M; Thomas, Rhys H; Rapps, Nora; Syrbe, Steffen; Dorn, Thomas; Lemke, Johannes R

    2016-09-01

    Prompted by the observations of juvenile myoclonic epilepsy (JME) in 22q11.2 deletion syndrome (22q11DS) and recurrent copy number variants in genetic generalized epilepsy (GGE), we searched for further evidence supporting a possible correlation of 22q11DS with GGE and with myoclonic seizures. Through routine diagnostics, we identified 3 novel individuals with the seemingly uncommon combination of 22q11DS and JME. We subsequently screened the literature for reports focussing on the epilepsy phenotype in 22q11DS. We additionally screened a database of 173 22q11DS patients and identified a fourth individual with JME as well as 2 additional cases with GGE. We describe 6 novel and 22 published cases with co-occurrence of 22q11DS and GGE. In many patients, GGE was associated with myoclonic seizures allowing for a diagnosis of JME in at least 6 individuals. Seventeen of the 173 22q11DS cases (10%) had a diagnosis of either focal or generalized epilepsy. In these cases, focal epilepsy could often be attributed to syndrome-associated hypocalcaemia, cerebral bleeds, or structural brain anomalies. However, the cause of GGE remained unclear. In this study, we describe and review 28 individuals with 22q11DS and GGE (especially JME), showing that both disorders frequently co-occur. Compared to the reported prevalence of 15-21%, in our case series only 10% of 22q11DS individuals were found to have epilepsy, often GGE. Since 22q11.2 does not contain convincing GGE candidate genes, we discuss the possibility of an aetiological correlation through a possibly disturbed interaction with the GABA B receptor.

  10. Platybasia in 22q11.2 Deletion Syndrome Is Not Correlated with Speech Resonance

    Directory of Open Access Journals (Sweden)

    Nicole E Spruijt

    2014-07-01

    Full Text Available Background An abnormally obtuse cranial base angle, also known as platybasia, is a common finding in patients with 22q11.2 deletion syndrome (22q11DS. Platybasia increases the depth of the velopharynx and is therefore postulated to contribute to velopharyngeal dysfunction. Our objective was to determine the clinical significance of platybasia in 22q11DS by exploring the relationship between cranial base angles and speech resonance. Methods In this retrospective chart review at a tertiary hospital, 24 children (age, 4.0-13.1 years with 22q11.2DS underwent speech assessments and lateral cephalograms, which allowed for the measurement of the cranial base angles. Results One patient (4% had hyponasal resonance, 8 (33% had normal resonance, 10 (42% had hypernasal resonance on vowels only, and 5 (21% had hypernasal resonance on both vowels and consonants. The mean cranial base angle was 136.5° (standard deviation, 5.3°; range, 122.3-144.8°. The Kruskal-Wallis test showed no significant relationship between the resonance ratings and cranial base angles (P=0.242. Cranial base angles and speech ratings were not correlated (Spearman correlation=0.321, P=0.126. The group with hypernasal resonance had a significantly more obtuse mean cranial base angle (138° vs. 134°, P=0.049 but did not have a greater prevalence of platybasia (73% vs. 56%, P=0.412. Conclusions In this retrospective chart review of patients with 22q11DS, cranial base angles were not correlated with speech resonance. The clinical significance of platybasia remains unknown.

  11. Pediatric healthcare costs for patients with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Benn, Peter; Iyengar, Sushma; Crowley, Terrence Blaine; Zackai, Elaine H; Burrows, Evanette K; Moshkevich, Solomon; McDonald-McGinn, Donna M; Sullivan, Kathleen E; Demko, Zachary

    2017-11-01

    The 22q11.2 deletion syndrome is a variably expressed disorder that can include cardiac, palate, and other physical abnormalities, immunodeficiency, and hypocalcemia. Because of the extreme variability in phenotype, there has been no available estimate of the total medical expenditure associated with the average case. We have developed a model to estimate the cost from the time of diagnosis to age 20. Costs were based on patients seen at a specialty center but also considered those components of care expected to have been provided by external healthcare facilities. Expense was based on billed medical charges extracted from the electronic medical billing system for all patients with a diagnosis of DiGeorge or velocardiofacial syndrome from 1993-2015. Expenditures included maternal prenatal care directly related to an affected pregnancy, molecular/cytogenetic diagnosis, consultations, surgery, and/or other treatment and management. Most mental health services (except inpatient), therapy related to cognitive, behavioral, speech, pharmacy, and nonmedical costs (special education, vocational, respite, lost earnings) were not included. Data were available for 642 patients with 50.7% diagnosed prenatally or in the first year of life. The average cost for a patient was $727,178. Costs were highest for patients ascertained prenatally ($2,599,955) or in the first year of life ($1,043,096), those with cardiac abnormalities or referred for cardiac evaluation ($751,535), and patients with low T-cell counts ($1,382,222). This study demonstrates that there are significant medical costs associated with 22q11.2 deletion syndrome. © 2017 Natera. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  12. Signs of dysarthria in adults with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Persson, Christina; Laakso, Katja; Edwardsson, Hannah; Lindblom, Johanna; Hartelius, Lena

    2017-03-01

    The aim of the study was to investigate how adults with 22q11.2 deletion syndrome (22q11DS) performed on dysarthria and intelligibility tests compared with a control group. Ten participants with confirmed 22q11.2 deletion, five males and five females with a mean age of 31 years (range: 19-49), were compared with a control group matched for gender and age (five males and five females, mean age: 32 years, range: 19-49). Assessment of non-verbal and verbal tasks reflecting respiration, phonation, oral motor function, velopharyngeal function, articulation, and prosody was performed as well as the Swedish Test of Intelligibility (STI). All assessments were made by two raters; inter-rater and intra-rater reliability was acceptable. The participants with 22q11DS had significantly more problems than the control group on all investigated dimensions except the STI. Overall, the severity of their speech deviation was rated as mild to moderate. The largest difficulties were found regarding speech respiration, phonation, oral motor function, and velopharyngeal function. The results of the present study suggest that a neurological etiology could be added to the previously described structural etiology explaining the speech difficulties found in 22q11DS. Signs of difficulties in both speech motor planning and speech motor programming were found. Further studies are needed to confirm the results, as are studies of the association between structural brain abnormalities and neurological speech symptoms. For clinical purposes, it is important that clinicians have knowledge about the variable speech symptoms that may occur in individuals with 22q11DS and that they be aware of the complexity of the etiology of such speech symptoms. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Çoruh Havza’sındaki Günlük Maksimum Yağış Serilerinin Trend Analizi

    OpenAIRE

    TOSUNOĞLU, Fatih

    2017-01-01

    Bu çalışmada, yıllık, mevsimlik ve aylık üç zaman dilimdeki günlük maksimum yağışların trendleriMann-Kendall (MK), modifye edilmiş Mann-Kendall (mMK), Theil-Sen (TH) ve Mann-Kendall Sıra Korelasyon(MKSK) testleri kullanılarak araştırılmıştır. Bu testler, Çoruh havzasında bulunan 5 adet istasyonun günlükmaksimum yağış verilerine uygulanmıştır. MK ve mMK testleri trendlerin anlamlılığını belirlemede, TH testitrendin büyüklüğünü hesaplamada ve MKSK testi ise ele alınan verilerdeki anlamlı trendl...

  14. Hyperfine structure of the metastable p-barHe+ atom revealed by a laser-induced (n,l) = (37,35) → (38,34) transition

    International Nuclear Information System (INIS)

    Widmann, E.; Eades, J.; Yamazaki, T.

    1996-11-01

    A precise scan of the previously discovered laser-induced transition (n,l) = (37,35) → (38,34) in p-barHe + revealed a doublet structure with a separation of Δν HF = 1.70 ± 0.05 GHz. This new type of 'hyperfine' splitting is ascribed to the interaction of the antiproton orbital angular momentum and the electron spin. (author)

  15. Enderunlu Vâsıf’ın “Gönlümdeki” Redifli Gazelinde Tasavvufî Söylem* Sufistic Discourse in “Gönlümdeki” Rhymed Gazelle by Enderunlu Vasıf Named

    Directory of Open Access Journals (Sweden)

    Ahmet DOĞAN

    2012-09-01

    Full Text Available In all sources he is mentioned, Enderunlu Vasıf, one of the last period figures of Divan literature, is defined as a poet followed in wake that Nedim marked a century ago. Enderunlu Vasıf is regarded as “a simple imitation of Nedim” and said to be mundaneness when he digresses the grace of Nedim-like discourse. In addition, he is said to have presented a hopeless, debauched, bohemian personality in his poems. But Enderunlu Vasıf, is evaluated as “a man at a moderate level who trained with the former discipline” and his work as seen in “above all certificate of disintegration to enjoy”. From time totime we witness that he shelters the peaceful climate of Sufism by expressing the spiritual alienation caused by the sociocultural changes of his era in Sufistic discourse. Enderunlu Vasıf's the attitudes of cynical, reckless and unbuttoned is as well as is seen as one who is equally caring of the life and art. For this reason, he appears as two different mood. This situation creates the impression that the poems were written by two different poets. It is possible to observe this ambivalent structure, seen both in feelings and poems of Enderunlu Vasıf, in “gönlümdeki” rhymed gazelle more distinctly. In the poem, virtual and esoteric “I” perception is revealed; and contrary to expectations, by addressing “esoteric I”, gazelle is presented to attention in sufistic profundity. Divan edebiyatının son dönem şahsiyetlerinden olan Enderunlu Vâsıf, isminin geçtiği hemen bütün kaynaklarda, yüz yıl önce Nedîm’in açmış olduğu çığırda yürüyen bir şair olarak tanımlanır. Kendisinden “Nedim’in basit bir kopyası” olarak bahsedilen ve kimi zaman “Nedîmâne” söyleyişteki zarafetten uzaklaşarak bayağılığa düştüğü kaydedilen Enderunlu Vâsıf’ın, şiirlerinde daha çok umursamaz, zevke ve eğlenceye düşkün, hayatı ciddiye almayan bir kişilik sergilediği söylenir. Ancak

  16. Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study

    Directory of Open Access Journals (Sweden)

    Daniel S. Tylee

    2017-01-01

    Full Text Available Chromosome 22q11.2 deletion syndrome (22q11.2DS is a genetic neurodevelopmental syndrome that has been studied intensively in order to understand relationships between the genetic microdeletion, brain development, cognitive function, and the emergence of psychiatric symptoms. White matter microstructural abnormalities identified using diffusion tensor imaging methods have been reported to affect a variety of neuroanatomical tracts in 22q11.2DS. In the present study, we sought to combine two discovery-based approaches: (1 white matter query language was used to parcellate the brain's white matter into tracts connecting pairs of 34, bilateral cortical regions and (2 the diffusion imaging characteristics of the resulting tracts were analyzed using a machine-learning method called support vector machine in order to optimize the selection of a set of imaging features that maximally discriminated 22q11.2DS and comparison subjects. With this unique approach, we both confirmed previously-recognized 22q11.2DS-related abnormalities in the inferior longitudinal fasciculus (ILF, and identified, for the first time, 22q11.2DS-related anomalies in the middle longitudinal fascicle and the extreme capsule, which may have been overlooked in previous, hypothesis-guided studies. We further observed that, in participants with 22q11.2DS, ILF metrics were significantly associated with positive prodromal symptoms of psychosis.

  17. Isoform-specific effects of a novel BmK 11(2) peptide toxin on Na channels.

    Science.gov (United States)

    Kondratiev, Andrei; Hahin, Richard; Tomaselli, Gordon F

    2003-03-01

    BmK 11(2) is a 7216Da polypeptide toxin purified from the venom of the scorpion Buthus martensii Karsch. Nanomolar concentrations of the toxin prolong amphibian nerve action potentials without attenuation of the amplitude. The pharmacological action of the toxin and its sequence similarity to other alpha-scorpion toxins suggest that BmK 11(2) selectively alters voltage-gated Na channels. In order to test whether BmK 11(2) preferentially modulates the gating or kinetics of certain channel isoforms, we applied BmK 11(2) to muscle, heart and neuronal Na channels. 100nM BmK 11(2) increased the peak current amplitude of skeletal muscle (micro1) and neuronal (N1E-115) Na currents by 40 and 20%, respectively, and reduced the cardiac Na (hH1) current by 15%. The toxin slowed current decay of all isoforms, most prominently in N1E-115 (tau(BmK)/tau(Control)=12), micro1 (11), and less so for hH1 (1.3). BmK 11(2) shifted the voltage dependence of activation of micro1 and N1E-115 currents. BmK 11(2) had no effect on steady-state inactivation, use-dependent availability, and the kinetics of entry into slowly recovering inactivated states.

  18. Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study.

    Science.gov (United States)

    Tylee, Daniel S; Kikinis, Zora; Quinn, Thomas P; Antshel, Kevin M; Fremont, Wanda; Tahir, Muhammad A; Zhu, Anni; Gong, Xue; Glatt, Stephen J; Coman, Ioana L; Shenton, Martha E; Kates, Wendy R; Makris, Nikos

    2017-01-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental syndrome that has been studied intensively in order to understand relationships between the genetic microdeletion, brain development, cognitive function, and the emergence of psychiatric symptoms. White matter microstructural abnormalities identified using diffusion tensor imaging methods have been reported to affect a variety of neuroanatomical tracts in 22q11.2DS. In the present study, we sought to combine two discovery-based approaches: (1) white matter query language was used to parcellate the brain's white matter into tracts connecting pairs of 34, bilateral cortical regions and (2) the diffusion imaging characteristics of the resulting tracts were analyzed using a machine-learning method called support vector machine in order to optimize the selection of a set of imaging features that maximally discriminated 22q11.2DS and comparison subjects. With this unique approach, we both confirmed previously-recognized 22q11.2DS-related abnormalities in the inferior longitudinal fasciculus (ILF), and identified, for the first time, 22q11.2DS-related anomalies in the middle longitudinal fascicle and the extreme capsule, which may have been overlooked in previous, hypothesis-guided studies. We further observed that, in participants with 22q11.2DS, ILF metrics were significantly associated with positive prodromal symptoms of psychosis.

  19. The Effectiveness and Safety of Antipsychotic and Antidepressant Medications in Individuals with 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Dori, Netta; Green, Tamar; Weizman, Abraham; Gothelf, Doron

    2017-02-01

    The purpose of this study was to evaluate the effectiveness and safety of antipsychotic and antidepressant medications in individuals with 22q11.2 deletion syndrome (22q11.2 DS) and psychiatric comorbidity. We used a record review, structured clinical interviews, and the Clinical Global Impressions (CGI) scale to retrospectively assess the effectiveness and safety of antipsychotic medications for schizophrenia spectrum disorders and of antidepressant medications for depressive and anxiety disorders in 40 individuals with 22q11.2DS. We observed significant improvement in CGI-Severity scores in individuals with 22q11.2DS treated with antipsychotic or antidepressant medications, and a ∼50% response rate based on the CGI-Improvement score. Adverse events were similar in types and rates to those reported in non-22q11.2 individuals treated with antipsychotics or antidepressants. Our data show that treatment with antipsychotics and antidepressants may be effective while being relatively safe in individuals with 22q11.2DS. Antipsychotic and antidepressant medications should be considered in any individual with 22q11.2DS who has a psychiatric morbidity, such as psychosis or mood or anxiety disorders. Although the psychotropic medications were generally well tolerated in our sample, more rigorous metabolic and cardiovascular measures are required in future studies to conclusively verify the safety of these medications.

  20. Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome.

    Science.gov (United States)

    Nilsson, Simon Ro; Fejgin, Kim; Gastambide, Francois; Vogt, Miriam A; Kent, Brianne A; Nielsen, Vibeke; Nielsen, Jacob; Gass, Peter; Robbins, Trevor W; Saksida, Lisa M; Stensbøl, Tine B; Tricklebank, Mark D; Didriksen, Michael; Bussey, Timothy J

    2016-10-01

    A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome (22q11.2DS) may model the genetic basis of cognitive deficits relevant for neuropsychiatric disorders such as schizophrenia. To assess the models usefulness for drug discovery, a novel mouse (Df(h22q11)/+) was assessed in an extensive battery of cognitive assays by partners within the NEWMEDS collaboration (Innovative Medicines Initiative Grant Agreement No. 115008). This battery included classic and touchscreen-based paradigms with recognized sensitivity and multiple attempts at reproducing previously published findings in 22q11.2DS mouse models. This work represents one of the most comprehensive reports of cognitive functioning in a transgenic animal model. In accordance with previous reports, there were non-significant trends or marginal impairment in some tasks. However, the Df(h22q11)/+ mouse did not show comprehensive deficits; no robust impairment was observed following more than 17 experiments and 14 behavioral paradigms. Thus - within the current protocols - the 22q11.2DS mouse model fails to mimic the cognitive alterations observed in human 22q11.2 deletion carriers. We suggest that the 22q11.2DS model may induce liability for cognitive dysfunction with additional "hits" being required for phenotypic expression. © The Author 2016. Published by Oxford University Press.

  1. Speech and language abilities of children with the familial form of 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Rakonjac Marijana

    2016-01-01

    Full Text Available The 22q11.2 Deletion Syndrome (22q11.2DS, which encompasses Shprintzen syndrome, DiGeorge and velocardiofacial syndrome, is the most common microdeletion syndrome in humans with an estimated incidence of approximately 1/4000 per live births. After Down syndrome, it is the second most common genetic syndrome associated with congenital heart malformations. The mode of inheritance of the 22q11.2DS is autosomal dominant. In approximately 72 - 94% of the cases the deletion has occurred de novo, while in 6 to 28% of patients deletion was inherited from a parent. As a part of a multidisciplinary study we examined the speech and language abilities of members of two families with inherited form of 22q11.2DS. The presence of 22q11.2 microdeletion was revealed by fluorescence in situ hybridization (FISH and/or multiplex ligation-dependent probe amplification (MLPA. In one family we detected 1.5 Mb 22q11.2 microdeletion, while in the other family we found 3Mb microdeletion. Patients from both families showed delays in cognitive, socio-emotional, speech and language development. Furthermore, we found considerable variability in the phenotypic characteristics of 22q11.2DS and the degree of speech-language pathology not only between different families with 22q11.2 deletion, but also among members of the same family. In addition, we detected no correlation between the phenotype and the size of 22q11.2 microdeletion.

  2. MicroRNA Dysregulation, Gene Networks, and Risk for Schizophrenia in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Merico, Daniele; Costain, Gregory; Butcher, Nancy J.; Warnica, William; Ogura, Lucas; Alfred, Simon E.; Brzustowicz, Linda M.; Bassett, Anne S.

    2014-01-01

    The role of microRNAs (miRNAs) in the etiology of schizophrenia is increasingly recognized. Microdeletions at chromosome 22q11.2 are recurrent structural variants that impart a high risk for schizophrenia and are found in up to 1% of all patients with schizophrenia. The 22q11.2 deletion region overlaps gene DGCR8, encoding a subunit of the miRNA microprocessor complex. We identified miRNAs overlapped by the 22q11.2 microdeletion and for the first time investigated their predicted target genes, and those implicated by DGCR8, to identify targets that may be involved in the risk for schizophrenia. The 22q11.2 region encompasses seven validated or putative miRNA genes. Employing two standard prediction tools, we generated sets of predicted target genes. Functional enrichment profiles of the 22q11.2 region miRNA target genes suggested a role in neuronal processes and broader developmental pathways. We then constructed a protein interaction network of schizophrenia candidate genes and interaction partners relevant to brain function, independent of the 22q11.2 region miRNA mechanisms. We found that the predicted gene targets of the 22q11.2 deletion miRNAs, and targets of the genome-wide miRNAs predicted to be dysregulated by DGCR8 hemizygosity, were significantly represented in this schizophrenia network. The findings provide new insights into the pathway from 22q11.2 deletion to expression of schizophrenia, and suggest that hemizygosity of the 22q11.2 region may have downstream effects implicating genes elsewhere in the genome that are relevant to the general schizophrenia population. These data also provide further support for the notion that robust genetic findings in schizophrenia may converge on a reasonable number of final pathways. PMID:25484875

  3. Reproductive Health Issues for Adults with a Common Genomic Disorder: 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Chan, Chrystal; Costain, Gregory; Ogura, Lucas; Silversides, Candice K.; Chow, Eva W.C.

    2015-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. Survival to reproductive age and beyond is now the norm. Several manifestations of this syndrome, such as congenital cardiac disease and neuropsychiatric disorders, may increase risk for adverse pregnancy outcomes in the general population. However, there are limited data on reproductive health in 22q11.2DS. We performed a retrospective chart review for 158 adults with 22q11.2DS (75 male, 83 female; mean age 34.3 years) and extracted key variables relevant to pregnancy and reproductive health. We present four illustrative cases as brief vignettes. There were 25 adults (21>age 35 years; 21 female) with a history of one or more pregnancies. Outcomes for women with 22q11.2DS, compared with expectations for the general population, showed a significantly elevated prevalence of small for gestational age liveborn offspring (p22q11.2 deletion. Recurring issues relevant to reproductive health in 22q11.2DS included the potential impact of maternal morbidities, inadequate social support, unsafe sexual practices, and delayed diagnosis of 22q11.2DS and/or lack of genetic counseling. These preliminary results emphasize the importance of early diagnosis and long term follow-up that could help facilitate genetic counseling for men and women with 22q11.2DS. We propose initial recommendations for pre-conception management, educational strategies, pre-natal planning, and preparation for possible high-risk pregnancy and/or delivery. PMID:25579115

  4. More Clinical Overlap between 22q11.2 Deletion Syndrome and CHARGE Syndrome than Often Anticipated

    Science.gov (United States)

    Corsten-Janssen, N.; Saitta, S.C.; Hoefsloot, L.H.; McDonald-McGinn, D.M.; Driscoll, D.A.; Derks, R.; Dickinson, K.A.; Kerstjens-Frederikse, W.S.; Emanuel, B.S.; Zackai, E.H.; van Ravenswaaij-Arts, C.M.A.

    2013-01-01

    CHARGE (coloboma, heart defects, atresia of choanae, retardation of growth and development, genital hypoplasia, and ear abnormalities) and 22q11.2 deletion syndromes are variable, congenital malformation syndromes that show considerable phenotypic overlap. We further explored this clinical overlap and proposed recommendations for the genetic diagnosis of both syndromes. We described 2 patients clinically diagnosed with CHARGE syndrome, who were found to carry a 22q11.2 deletion, and searched the literature for more cases. In addition, we screened our cohort of CHD7 mutation carriers (n = 802) for typical 22q11.2 deletion features and studied CHD7 in 20 patients with phenotypically 22q11.2 deletion syndrome but without haploinsufficiency of TBX1. In total, we identified 5 patients with a clinical diagnosis of CHARGE syndrome and a proven 22q11.2 deletion. Typical 22q11.2 deletion features were found in 30 patients (30/802, 3.7%) of our CHD7 mutation-positive cohort. We found truncating CHD7 mutations in 5/20 patients with phenotypically 22q11.2 deletion syndrome. Differentiating between CHARGE and 22q11.2 deletion syndromes can be challenging. CHD7 and TBX1 probably share a molecular pathway or have common target genes in affected organs. We strongly recommend performing CHD7 analysis in patients with a 22q11.2 deletion phenotype without TBX1 haploinsufficiency and conversely, performing a genome-wide array in CHARGE syndrome patients without a CHD7 mutation. PMID:23885230

  5. Improving the Diagnosis of Children with 22q11.2 Deletion Syndrome: A Single-center Experience from Serbia.

    Science.gov (United States)

    Cuturilo, Goran; Drakulic, Danijela; Jovanovic, Ida; Krstic, Aleksandar; Djukic, Milan; Skoric, Dejan; Mijovic, Marija; Stefanovic, Igor; Milivojevic, Milena; Stevanovic, Milena

    2016-09-08

    The incidence of the 22q11.2 microdeletion among children who have at least two out of five major clinical criteria for 22q11.2 deletion syndrome. Prospective study. University Childrens Hospital in Belgrade, Serbia between 2005 and 2014. 57 patients with clinical characteristics of 22q11.2 deletion syndrome. Standard G-banding cytogenetic analysis was performed in all children, and the 22q11.2 genomic region was examined using fluorescence in situ hybridization (FISH). For patients with no deletion detected by FISH, multiplex ligation-dependent probe amplification (MLPA) analysis was also done in order to detect cryptic deletions of this region and to analyze other genomic loci associated with phenotypes resembling the syndrome. A selected group of patients diagnosed to have 22q11.2 microdeletion by FISH underwent MLPA testing in order to characterize the size and position of deletion. The frequency of 22q11.2 microdeletion among children with at least two of the five major characteristics of 22q11.2 deletion syndrome (heart malformations, facial dysmorphism, T-cell immunodeficiency, palatal clefts and hypocalcemia/hypoparathyroidism). Typical 22q11.2 microdeletion was detected in 42.1% of patients; heart malformation were identified in all of them, facial dysmorphism in 79.2%, immunological problems in 63.6%, hypocalcemia in 62.5% and cleft palate in 8.3%. A higher detection rate compared to one-feature criterion is obtained when at least two major features of 22q11.2 deletion syndrome are taking into consideration. The criteria applied in this study could be considered by centers in low-income countries.

  6. MicroRNA dysregulation, gene networks and risk for schizophrenia in 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Daniele eMerico

    2014-11-01

    Full Text Available The role of microRNAs (miRNAs in the aetiology of schizophrenia is increasingly recognized. Microdeletions at chromosome 22q11.2 are recurrent structural variants that impart a high risk for schizophrenia and are found in up to 1% of all patients with schizophrenia. The 22q11.2 deletion region overlaps gene DGCR8, encoding a subunit of the miRNA microprocessor complex. We identified miRNAs overlapped by the 22q11.2 microdeletion and for the first time investigated their predicted target genes, and those implicated by DGCR8, to identify targets that may be involved in the risk for schizophrenia. The 22q11.2 region encompasses seven validated or putative miRNA genes. Employing two standard prediction tools, we generated sets of predicted target genes. Functional enrichment profiles of the 22q11.2 region miRNA target genes suggested a role in neuronal processes and broader developmental pathways. We then constructed a protein interaction network of schizophrenia candidate genes and interaction partners relevant to brain function, independent of the 22q11.2 region miRNA mechanisms. We found that the predicted gene targets of the 22q11.2 deletion miRNAs, and targets of the genome-wide miRNAs predicted to be dysregulated by DGCR8 hemizygosity, were significantly represented in this schizophrenia network. The findings provide new insights into the pathway from 22q11.2 deletion to expression of schizophrenia, and suggest that hemizygosity of the 22q11.2 region may have downstream effects implicating genes elsewhere in the genome that are relevant to the general schizophrenia population. These data also provide further support for the notion that robust genetic findings in schizophrenia may converge on a reasonable number of final pathways.

  7. How to diagnose the 22q11.2 deletion syndrome in patients with schizophrenia: a case report

    Science.gov (United States)

    2013-01-01

    The 22q11.2 deletion syndrome is caused by a microdeletion of chromosome 22. One third of all patients with 22q11.2 deletion develop schizophrenia-like symptoms. In general, the prevalence of 22q11.2 deletion in patients with schizophrenia is 1%–2%. The 22q11.2 deletion is one of the major known genetic risk factors for schizophrenia. However, clinical differences in the phenotypes between patients with schizophrenia who are 22q11.2 deletion carriers and those who are not are still unknown. Therefore, it may be difficult to diagnose 22q11.2 deletion in patients with schizophrenia on the basis of clinical symptoms. To date, only two Japanese patients with the deletion have been identified through microdeletion studies of patients with schizophrenia in the Japanese population. Herein, we report the case study of a 48-year-old Japanese woman with 22q11.2 deletion who had a 30-year history of schizophrenia. Based on craniofacial anomalies, unpredictable agitation, hypocalcemia, and brain imaging finding, we suspected the 22q11.2 deletion in clinical populations and diagnosed the deletion using fluorescence in situ hybridization analysis. To find common phenotypes in Japanese patients with the deletion who have schizophrenia-like symptoms, we compared phenotypes among three Japanese cases. The common phenotypes were an absence of congenital cardiovascular anomalies and the presence of current findings of low intellectual ability, agitation, and hypocalcemia. We propose that hypocalcemia and agitation in patients with schizophrenia may derive from the 22q11.2 deletion, particularly when these phenotypes are coupled with schizophrenia-like symptoms. PMID:24063534

  8. Clinicopathologic Characteristics and Prognosis of Xp11.2 Translocation Renal Cell Carcinoma: Multicenter, Propensity Score Matching Analysis.

    Science.gov (United States)

    Choo, Min Soo; Jeong, Chang Wook; Song, Cheryn; Jeon, Hwang Gyun; Seo, Seong Il; Hong, Sung Kyu; Byun, Seok-Soo; Chung, Jin Soo; Hong, Sung-Hoo; Hwang, Eu Chang; Kim, Hyeon Hoe; Kwak, Cheol

    2017-10-01

    We evaluated the clinicopathologic characteristics and prognosis of Xp11.2 translocation (Xp11.2t) renal cell carcinoma (RCC) from a multicenter study and compare them with clear-cell RCC using a propensity score matching analysis. Between 2004 and 2013, 8384 consecutive patients from 7 institutions who were diagnosed with RCC were reviewed, and the pathologically confirmed Xp11.2t cases were enrolled. The oncological outcomes of Xp11.2t were compared with those of clear-cell RCC by selecting matched cases using 1:3 propensity score matching methods in a precollected clear-cell RCC data set from our hospital. The patients were divided into 2 subgroups on the basis of age of onset, either before (early) or after (late) 45 years old. Xp11.2t was found in 61 cases, corresponding to 0.72% of RCC cases for the 10 years. The mean age was 38.2 ± 19.4 years, and the mean tumor size was 6.2 ± 3.9 cm. The Xp11.2t cases were at more advanced stages and showed tendencies to involve lymph nodes at diagnosis. After the matching, there were no significant differences in recurrence-free and overall survival compared with clear-cell RCC. The age of incidence for Xp11.2t had a bimodal distribution, which was most common in the 30s and smaller peak in the 60s. Xp11.2t corresponded to a significantly worse prognosis for overall survival in late onset (after 45 years) subgroup (P = .038; hazard ratio, 3.199; 95% confidence interval, 1.065-9.609). This neoplasm has more aggressive clinicopathologic features at diagnosis. In older patients with onset age > 45 years, Xp11.2t showed a significantly worse prognosis than clear-cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Technical principles underlying limit values for release of substances for the percolation test TS3: comparison DE and NL

    Energy Technology Data Exchange (ETDEWEB)

    Van Zomeren, A.; Dijkstra, J.J. [ECN Environment and Energy Engineering, Petten (Netherlands); Susset, B. [Consulting Office SiWaP (Germany)

    2013-10-15

    Within CEN TC 351 WG 1, standardized, horizontal test methods are developed to assess the release (leaching) of dangerous substances from construction as defined in ER3 of the CPD. For granular materials TS 3, a horizontal up-flow percolation test, was further developed by CEN TC 351 WG1 and will enter the validation phase in 2013. In CEN TC 351 WG1, there are still discussions regarding the sample preparation and some test conditions. Currently, two options for sample preparation and test conditions are specified. Controversy between DE and NL regarding sample preparation and test conditions and the need for two separate options in the TS 3 percolation test are possibly for a part caused by different approaches for risk assessment in the Netherlands and in Germany and the resulting regulatory concepts. One important reason for this is, that in soil and groundwater regulations the test method and the impact assessment method are systematically linked together but the impact assessment methods and lab methods in both countries are different. The discussions in CEN TC 351 WG 1 show that there is a need to have a better mutual understanding of the relation between test method and impact assessment on the one hand and a clear overview of differences in impact assessment approaches of each country on the other hand. The aim of this project is to explain and compare the assumptions, boundary conditions and conventions of the impact assessment approach that are implemented in the upcoming German Recycling Degree and in the Soil Quality Degree of the Netherlands. Ultimately, a better understanding of the impact assessment approaches provides a basis for further discussion in WG1 to agree on only one option for the percolation test conditions. The following report is prepared by the contractors of Germany and Netherlands together to compare the two country-specific concepts. This report summarizes and explains the presentation given on the 25th of April at TC 351 WG1 in

  10. Depleted and enriched uranium exposure quantified in former factory workers and local residents of NL Industries, Colonie, NY USA

    International Nuclear Information System (INIS)

    Arnason, John G.; Pellegri, Christine N.; Moore, June L.; Lewis-Michl, Elizabeth L.; Parsons, Patrick J.

    2016-01-01

    Background: Between 1958 and 1982, NL Industries manufactured components of enriched (EU) and depleted uranium (DU) at a factory in Colonie NY, USA. More than 5 metric tons of DU was deposited as microscopic DU oxide particles on the plant site and surrounding residential community. A prior study involving a small number of individuals (n=23) indicated some residents were exposed to DU and former workers to both DU and EU, most probably through inhalation of aerosol particles. Objectives: Our aim was to measure total uranium [U] and the uranium isotope ratios: 234 U/ 238 U; 235 U/ 238 U; and 236 U/ 238 U, in the urine of a cohort of former workers and nearby residents of the NLI factory, to characterize individual exposure to natural uranium (NU), DU, and EU more than 3 decades after production ceased. Methods: We conducted a biomonitoring study in a larger cohort of 32 former workers and 99 residents, who may have been exposed during its period of operation, by measuring Total U, NU, DU, and EU in urine using Sector Field Inductively Coupled Plasma - Mass Spectrometry (SF-ICP-MS). Results: Among workers, 84% were exposed to DU, 9% to EU and DU, and 6% to natural uranium (NU) only. For those exposed to DU, urinary isotopic and [U] compositions result from binary mixing of NU and the DU plant feedstock. Among residents, 8% show evidence of DU exposure, whereas none shows evidence of EU exposure. For residents, the [U] geometric mean is significantly below the value reported for NHANES. There is no significant difference in [U] between exposed and unexposed residents, suggesting that [U] alone is not a reliable indicator of exposure to DU in this group. Conclusions: Ninety four percent of workers tested showed evidence of exposure to DU, EU or both, and were still excreting DU and EU decades after leaving the workforce. The study demonstrates the advantage of measuring multiple isotopic ratios (e.g., 236 U/ 238 U and 235 U/ 238 U) over a single ratio ( 235 U/ 238 U

  11. Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome

    DEFF Research Database (Denmark)

    Starnawska, A; Hansen, C S; Sparsø, T

    2017-01-01

    Individuals with 22q11.2 deletion syndrome (DS) have an increased risk of comorbid mental disorders including schizophrenia, attention deficit hyperactivity disorder, depression, as well as intellectual disability. Although most 22q11.2 deletion carriers have the long 3-Mb form of the hemizygous...... deletion, there remains a large variation in the development and progression of psychiatric disorders, which suggests that alternative factors contribute to the pathogenesis. In this study we investigated whether neonatal DNA methylation signatures in individuals with the 22q11.2 deletion associate...

  12. Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data

    Science.gov (United States)

    Mok, Kin Y; Sheerin, Una; Simón-Sánchez, Javier; Salaka, Afnan; Chester, Lucy; Escott-Price, Valentina; Mantripragada, Kiran; Doherty, Karen M; Noyce, Alastair J; Mencacci, Niccolo E; Lubbe, Steven J; Williams-Gray, Caroline H; Barker, Roger A; van Dijk, Karin D; Berendse, Henk W; Heutink, Peter; Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis; Brockmann, Kathrin; Schulte, Claudia; Gasser, Thomas; Foltynie, Thomas; Limousin, Patricia; Morrison, Karen E; Clarke, Carl E; Sawcer, Stephen; Warner, Tom T; Lees, Andrew J; Morris, Huw R; Nalls, Mike A; Singleton, Andrew B; Hardy, John; Abramov, Andrey Y; Plagnol, Vincent; Williams, Nigel M; Wood, Nicholas W

    2016-01-01

    Summary Background Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. Methods We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients. Findings We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32·0–55·5; mean 42·1 years [SD 11·9]) than in those who did not carry a deletion (median 61 years, 95% CI 60·5–61·0; mean 60·3 years [SD 12·8]). A 22q11.2 deletion was present in more patients with early-onset (p22q11.2 deletions in patients with Parkinson's disease who have early presentation or features associated with the chromosome 22q11.2 deletion syndrome, or both. Funding UK Medical Research Council, UK Wellcome Trust, Parkinson's UK, Patrick Berthoud

  13. The benefits and limitations of cell-free DNA screening for 22q11.2 deletion syndrome.

    Science.gov (United States)

    Dugoff, Lorraine; Mennuti, Michael T; McDonald-McGinn, Donna M

    2017-01-01

    Cell-free DNA testing is increasingly being used to screen pregnant women for fetal aneuploidy. This technology may also identify microdeletion syndromes, including 22q11.2 deletion syndrome, the most common microdeletion syndrome, and the 22q11.2 duplication syndrome. The purpose of this paper is to provide an overview of the 22q11.2 deletion syndrome, to review the early experience with cell-free DNA screening for this deletion and to consider the potential benefits that may be associated with prenatal detection of the deletion. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  14. Severe laryngeal stenosis in newly born twins with 22q11.2 deletion syndrome: A case report.

    Science.gov (United States)

    Clive, B; Corsten, G; Penney, L S; Van den Hof, M; El-Naggar, W

    2016-05-18

    Chromosome 22q11.2 deletion syndrome is common and presents with a range of clinical features from cardiac malformations to hypocalcemia. Laryngeal anomalies are not a common feature of this syndrome. We describe newly born twins who presented with unexpected severe birth depression secondary to severe type IV glottic webs requiring extensive resuscitation and emergency tracheostomy. They were diagnosed postnatally to have deletion of 22q11.2. The successful resuscitation of these infants at birth was only possible because they were born in a tertiary care hospital. This report shows the critical nature of prenatal diagnosis of 22q11.2 deletion syndrome.

  15. Sievietes loma draudzes dievkalpojumā Korintā (1.Kor.11:2-16)

    OpenAIRE

    Borovko, Jevgenija

    2008-01-01

    Bakalaura darba nosaukums ir „Sievietes loma draudzes dievkalpojumā Korintā (1.Kor. 11:2-16)”. Darbā parādīts, kāda ir bijusi sievietes loma agrīnajā kristiešu draudzē. Darba mērķis ir parādīt, ka attiecībā uz pravietisko sludināšanu sievietes Korintas draudzes dievkalpojumā ir spēlējušas vienlīdzīgu lomu ar praviešiem vīriešiem. Darbs sastāv no ievada, četrām nodaļām – teksta ekseģēze, sievietes loma hellēnistiskajā pasaulē, pravietošanas fenomens, sieviešu loma Korintā, secinājumiem, kā arī...

  16. Psychiatric manifestations of 22q11.2 deletion syndrome: a literature review.

    Science.gov (United States)

    Bertrán, M; Tagle, F P; Irarrázaval, M

    2018-03-01

    The 22q11.2 deletion syndrome is a genetic disorder with variable clinical manifestations. It affects one out of 5950 neonates and has an autosomal dominant inheritance pattern. The aim of this article is to review its psychiatric manifestations and any underlying genetic alterations. We reviewed the scientific literature available as of October 2014 in the LILACS and Medline databases. Sixty per cent of these patients fulfilled diagnostic criteria for a mental disorder at some point in their lives, referring to psychotic disorders, attention deficit hyperactivity disorder, mood disorders, anxiety disorders, and autism spectrum disorders. Specific genes, such as COMT and PRODH, have been linked to these psychiatric manifestations. It is necessary to raise awareness among all health care professionals so that they understand the relevance of these manifestations, are able to anticipate them, and can provide appropriate information to patients and family members. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. 22q11.2 microdeletion syndrome as a multidisciplinary problem

    Directory of Open Access Journals (Sweden)

    Marta Skoczyńska

    2017-12-01

    Full Text Available 22q11.2 microdeletion syndrome, known also under the name of DiGeorge syndrome, is the most frequent deletion in the human chromosome. Its prevalence is estimated at about 1:9,700 newborns, but this is probably an underestimation. In over 90% of cases, the disease is caused by de novo microdeletion in the long arm of chromosome 22, and more rarely by microdeletion of the short arm of this chromosome or by a gene TBX1 point mutation. The consequences of these genotypic disorders are developmental anomalies of the third and fourth pharyngeal arches during the foetal life, which leads to abnormal development of the thymus, parathyroid glands and major cardiac vessels. The characteristic triad of symptoms includes a cardiac defect, hypocalcaemic tetany (hypoparathyroidism and immunodeficiency. The syndrome may also manifest as facial dysmorphia, palate defects, gastrointestinal abnormalities, urogenital malformations, autoimmune diseases and psychiatric disorders. Standard tests to diagnose this syndrome are molecular studies, such as fluorescence in situ hybridization, array comparative genomic hybridization and a type of polymerase chain reaction: multiplex ligationdependent probe amplification. The therapy of DiGeorge syndrome may include: calcium supplementation, surgical correction of cardiac and palate defects, treatment of immunodeficiency by injections of immunoglobulins, stem cell transplantation or, in rare cases, thymus transplantation. The management of DiGeorge syndrome requires a multidisciplinary approach. Early diagnosis and treatment significantly improve patient’s chances for normal functioning in adult life.

  18. High specificity PCR screening for 22q11.2 microdeletion in three different ethnic groups

    Directory of Open Access Journals (Sweden)

    A.C. Pereira

    2003-10-01

    Full Text Available Congenital heart defects are the most common of all human birth defects. Numerous studies have shown that a deletion within chromosome 22q11 is associated with DiGeorge syndrome and certain forms of sporadic congenital cardiovascular disease. We have determined the value of a PCR assay using markers D22S941, D22S944 and D22S264 designed for the screening of 22q11.2 deletion through consecutive homozygosity in an ethnically admixed urban population. The study population comprised 149 unrelated men and women from three different ethnic groups (white, mulatto and black. Test specificity for the overall population was estimated at 98.3%. We found no significant difference when comparing heterozygosity indices and ethnicity (P value = 0.43 (D22S944, 0.22 (D22S264, and 0.58 (D22S941. There was no significant difference regarding assay specificity between the three different ethnic groups studied. This assay could constitute a cost-effective way to screen a large number of patients at increased risk, since PCR techniques are easily available, are fast, can be automatized, and are significantly less expensive than fluorescence in situ hybridization.

  19. Three patients with oculo-auriculo-vertebral spectrum and microdeletion 22q11.2.

    Science.gov (United States)

    Digilio, M Cristina; McDonald-McGinn, Donna M; Heike, Carrie; Catania, Charles; Dallapiccola, Bruno; Marino, Bruno; Zackai, Elaine H

    2009-12-01

    We report on three unrelated patients with the 22q11.2 microdeletion syndrome (del22q11) who have phenotypic anomalies compatible with oculo-auriculo-vertebral spectrum (OAVS). Hemifacial microsomia, unilateral microtia, hearing loss, congenital heart/aortic arch arteries defects, and feeding difficulties were present in all three patients. Additional anomalies occasionally diagnosed included coloboma of the upper eyelid, microphthalmia, cerebral malformation, palatal anomalies, neonatal hypocalcemia, developmental delay, and laryngomalacia. Several clinical features characteristic of OAVS have been described in patients with del22q11 from the literature, including ear anomalies, hearing loss, cervical vertebral malformations, conotruncal cardiac defects, renal malformations, feeding and respiratory difficulties. Atretic ear with facial asymmetry has been previously described in one patient. Thus, clinical expression of hemifacial microsomia and microtia resembling OAVS should now be included within the wide phenotypic expression of del22q11. The occurrence of this manifestation in del22q11 is currently low. Nevertheless, patients with hemifacial microsomia and microtia associated with clinical features typically associated with del22q11 should now have for specific cytogenetic testing.

  20. New developments in Smith-Magenis syndrome (del 17p11.2).

    Science.gov (United States)

    Gropman, Andrea L; Elsea, Sarah; Duncan, Wallace C; Smith, Ann C M

    2007-04-01

    Recent clinical, neuroimaging, sleep, and molecular cytogenetic studies have provided new insights into the mechanisms leading to the Smith-Magenis phenotype and are summarized in this review. Cross sectional studies of patients with Smith-Magenis syndrome have found evidence for central and peripheral nervous system abnormalities, neurobehavioral disturbances, and an inverted pattern of melatonin secretion leading to circadian rhythm disturbance. A common chromosome 17p11.2 deletion interval spanning approximately 3.5 Mb is identified in about 70% of individuals with chromosome deletion. Recently heterozygous point mutations in the RAI1 gene within the Smith-Magenis syndrome critical region have been reported in Smith-Magenis syndrome patients without detectable deletion by fluorescent in-situ hybridization. Patients with intragenic mutations in RAI1 as well as those with deletions share most but not all aspects of the phenotype. Findings from molecular cytogenetic analysis suggest that other genes or genetic background may play a role in altering the functional availability of RAI1 for downstream effects. Further research into additional genes in the Smith-Magenis syndrome critical region will help define the role they play in modifying features or severity of the Smith-Magenis syndrome phenotype. More research is needed to translate advances in clinical research into new treatment options to address the sleep and neurobehavioral problems in this disorder.

  1. Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)

    Energy Technology Data Exchange (ETDEWEB)

    Greenberg, F.; Lewis, R.A.; Potocki, L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1996-03-29

    Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65% brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of the collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20-78, most patients falling in the moderate range of mental retardation at 40-54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter. 42 refs., 2 figs., 3 tabs.

  2. Deletion and duplication within the p11.2 region of chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, D.J.; McCorquodale, M.; Bereziouk, O. [Univ. of Illinois College of Medicine, Chicago, IL (United States)] [and others

    1994-09-01

    A 7 1/2-year-old male patient presented with mild mental retardation, speech delay, hyperactivity, behavioral problems, mild facial hypoplasia, short broad hands, digital anomalies, and self-injurious behavior. Chromosomes obtained from peripheral blood cells revealed a deletion of 17p11.2 in about 40% of the metaphases examined, suggesting that the patient had Smith-Magenis Syndrome. A similar pattern of mosaicism in peripheral blood cells, but not in fibroblasts in which all cells displayed the deletion, has been previously reported. Since some cases of Smith-Magenis Syndrome have a deletion that extends into the region associated with Charcot-Marie-Tooth (CMT) Syndrome, we examined interphase cells with a CMT1A-specific probe by the method of fluorescence in situ hybridization. The CMT1A region was not deleted, but about 40% of the cells gave signals indicating a duplication of the CMT1A region. The patient has not presented neuropathies associated with CMT at this time. Future tracking of the patient should be informative.

  3. FISICA Integral Field Spectroscopy of the Shocked Iron Gas in the Supernova Remnant G11.2--0.3

    Science.gov (United States)

    Moon, Dae-Sik; Eikenberry, Stephen S.; Koo, Bon-Chul; Raines, S. Nicholas; Gruel, Nicolas

    2006-02-01

    We have recently discovered strong iron line ([Fe II] (lambda)1.644 (mu)m) emission in the young supernova remnant G11.2-0.3. The iron line emission occurs at the south-eastern shell edge of G11.2-0.3, and positionally overlaps with the very strong X-ray and radio emission of the supernova remnant. The iron line emission is most likely caused by the shock acceleration of G11.2-0.3 interacting with the ambient medium. We propose to carry out JH-band integral-field spectroscopy of the two iron line clumps in G11.2-0.3 with FISICA, an image-slicing integral-field unit for FLAMINGOS, which will give us a uniquely comprehensive view of the strong shock acceleration of a SNR.

  4. Potential Role of Cortisol in Social and Memory Impairments in Individuals with 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Jacobson, Daniel; Bursch, Megan; Lajiness-O'Neill, Renee

    2016-01-01

    22q11.2 Deletion syndrome is a genetic disorder characterized by physiological and psychological symptoms. This study investigated the role of cortisol on the social and cognitive impairments in children with 22q11.2. A total of 11 children with 22q11.2 were assessed for baseline cortisol levels and received broad neuropsychological testing. Results were compared with 11 controls. Children with 22q11.2 had significantly higher cortisol levels. A significant negative correlation was observed between the general memory and attention/concentration indices of the Wide Range Assessment of Memory and Learning, 2nd edition and cortisol concentrations in the control population. These data provide evidence of a possible causal mechanism that underlies social impairments in stress disorders. PMID:27617156

  5. Cognitive behavioral therapy in 22q11.2 microdeletion with psychotic symptoms: What do we learn from schizophrenia?

    Science.gov (United States)

    Demily, Caroline; Franck, Nicolas

    2016-11-01

    The 22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes, with a widely underestimated prevalence between 1 per 2000 and 1 per 6000. Since childhood, patients with 22q11.2DS are described as having difficulties to initiate and maintain peer relationships. This lack of social skills has been linked to attention deficits/hyperactivity disorder, anxiety and depression. A high incidence of psychosis and positive symptoms is observed in patients with 22q11.2DS and remains correlated with poor social functioning, anxiety and depressive symptoms. Because 22q11.2DS and schizophrenia share several major clinical features, 22q11.2DS is sometimes considered as a genetic model for schizophrenia. Surprisingly, almost no study suggests the use of cognitive and behavioral therapy (CBT) in this indication. We reviewed what should be learned from schizophrenia to develop specific intervention for 22q11.2DS. In our opinion, the first step of CBT approach in 22q11.2DS with psychotic symptoms is to identify precisely which tools can be used among the already available ones. Cognitive behavioral therapy (CBT) targets integrated disorders, i.e. reasoning biases and behavior disorders. In 22q11.2DS, CBT-targeted behavior disorders may take the form of social avoidance and withdrawal or, in the contrary, a more unusual disinhibition and aggressiveness. In our experience, other negative symptoms observed in 22q11.2DS, such as motivation deficit or anhedonia, may also be reduced by CBT. Controlled trials have been studying the benefits of CBT in schizophrenia and several meta-analyses proved its effectiveness. Therefore, it is legitimate to propose this tool in 22q11.2DS, considering symptoms similarities. Overall, CBT is the most effective psychosocial intervention on psychotic symptoms and remains a relevant complement to pharmacological treatments such as antipsychotics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Neuroimaging and clinical features in adults with a 22q11.2 deletion at risk of Parkinson's disease.

    Science.gov (United States)

    Butcher, Nancy J; Marras, Connie; Pondal, Margarita; Rusjan, Pablo; Boot, Erik; Christopher, Leigh; Repetto, Gabriela M; Fritsch, Rosemarie; Chow, Eva W C; Masellis, Mario; Strafella, Antonio P; Lang, Anthony E; Bassett, Anne S

    2017-05-01

    The recurrent 22q11.2 deletion is a genetic risk factor for early-onset Parkinson's disease. Adults with the associated 22q11.2 deletion syndrome (22q11.2DS) may exhibit phenotypes that could help identify those at highest risk and reveal disease trajectories. We investigated clinical and neuroimaging features relevant to Parkinson's disease in 26 adults: 13 with 22q11.2DS at genetic risk of Parkinson's disease (mean age = 41.5 years, standard deviation = 9.7), 12 healthy age and sex-matched controls, and a 22q11.2DS patient with l-DOPA-responsive early-onset Parkinson's disease. Neuroimaging included transcranial sonography and positron emission tomography using 11C-dihydrotetrabenazine (11C-DTBZ), a radioligand that binds to the presynaptic vesicular monoamine transporter. The 22q11.2DS group without Parkinson's disease demonstrated significant motor and olfactory deficits relative to controls. Eight (61.5%) were clinically classified with parkinsonism. Transcranial sonography showed a significantly larger mean area of substantia nigra echogenicity in the 22q11.2DS risk group compared with controls (P = 0.03). The 22q11.2DS patient with Parkinson's disease showed the expected pattern of severely reduced striatal 11C-DTBZ binding. The 22q11.2DS group without Parkinson's disease however showed significantly elevated striatal 11C-DTBZ binding relative to controls (∼33%; P < 0.01). Results were similar within the 22q11.2DS group for those with (n = 7) and without (n = 6) psychotic illness. These findings suggest that manifestations of parkinsonism and/or evolution to Parkinson's disease in this genetic at-risk population may include a hyperdopaminergic mechanism. Adequately powered longitudinal studies and animal models are needed to evaluate the relevance of the observed clinical and imaging phenotypes to Parkinson's disease and other disorders that are more prevalent in 22q11.2DS, such as schizophrenia. © The Author (2017). Published by Oxford University Press

  7. The clinical presentation of attention deficit‐hyperactivity disorder (ADHD) in children with 22q11.2 deletion syndrome

    Science.gov (United States)

    Martin, Joanna; Thapar, Anita; Owen, Michael J.

    2015-01-01

    Background: Although attention deficit‐hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children with 22q11.2DS, it remains unclear whether its clinical presentation is similar to that in children with idiopathic ADHD. The aim of this study is to compare the ADHD phenotype in children with and without 22q11.2DS by examining ADHD symptom scores, patterns of psychiatric comorbidity, IQ and gender distribution. Methods: Forty‐four children with 22q11.2DS and ADHD (mean age = 9.6), 600 clinic children (mean age = 10.8) and 77 children with ADHD from a population cohort (mean age = 10.8) participated in the study. Psychopathology was assessed using parent‐report research diagnostic instruments. Results: There was a higher proportion of females in the 22q11.2DS ADHD sample in relation to the clinical sample (χ2 = 18.2, P ADHD inattentive subtype (χ2 = 114.76, P ADHD group parents reported fewer oppositional defiant disorder/conduct disorder symptoms (z = 6.33, P ADHD sample had received ADHD treatment. The results were similar when the 22q11.2 ADHD group was compared to the population cohort ADHD group. Conclusions: The clinical presentation of ADHD and patterns of co‐morbidity in 22q11.2DS is different from that in idiopathic ADHD. This could lead to clinical under‐recognition of ADHD in this group. Examining psychopathology in 22q11.2DS can provide insights into the genetic origins of psychiatric problems with implications beyond the 22q11.2DS population. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:26400629

  8. Developmental Course of Conversational Behaviour of Children with 22q11.2 Deletion Syndrome and Williams Syndrome

    Science.gov (United States)

    Van Den Heuvel, Ellen; Botting, Nicola; Boudewijns, Inge; Manders, Eric; Swillen, Ann; Zink, Inge

    2017-01-01

    This study investigated three conversational subskills in children with 22q11.2 deletion syndrome (22q11.2DS, n = 8, ages 7-13) and Williams syndrome (WS, n = 8, ages 6-12). The researchers re-evaluated these subskills after 18 to 24 months and compared them to those of peers with idiopathic intellectual disability (IID) and IID and comorbid…

  9. Manifestation of recessive combined D-2-, L-2-hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Eguchi, Mariko; Ozaki, Erina; Yamauchi, Toshifumi; Ohta, Masaaki; Higaki, Takashi; Masuda, Kiyoshi; Imoto, Issei; Ishii, Eiichi; Eguchi-Ishimae, Minenori

    2018-02-01

    22q11.2 deletion syndrome is one of the most common human microdeletion syndromes. The clinical phenotype of 22q11.2 deletion syndrome is variable, ranging from mild to life-threatening symptoms, depending mainly on the extent of the deleted region. Brain malformations described in association with 22q11.2 deletion syndrome include polymicrogyria, cerebellar hypoplasia, megacisterna magna, and agenesis of the corpus callosum (ACC), although these are rare. We report here for the first time a patient who manifested combined D-2- and L-2-hydroxyglutaric aciduria as a result of a hemizygous mutation in SLC25A1 in combination with 22q11.2 deletion. The girl was diagnosed to have ACC shortly after birth and a deletion of 22q11.2 was identified by genetic analysis. Although the patient showed cardiac anomalies, which is one of the typical symptoms of 22q11.2 deletion syndrome, her rather severe phenotype and atypical face prompted us to search for additional pathogenic mutations. Three genes present in the deleted 22q11.2 region, SLC25A1, TUBA8, and SNAP29, which have been reported to be associated with brain malformation, were analyzed for the presence of pathogenic mutations. A frameshift mutation, c.18_24dup (p.Ala9Profs*82), was identified in the first exon of the remaining SLC25A1 allele, resulting in the complete loss of normal SLC25A1 function in the patient's cells. Our results support the notion that the existence of another genetic abnormality involving the retained allele on 22q11.2 should be considered when atypical or rare phenotypes are observed. © 2017 Wiley Periodicals, Inc.

  10. The 22q11.2 Deletion Syndrome in Congenital Heart Defects: Prevalence of Microdeletion Syndrome in Cameroon.

    Science.gov (United States)

    Wonkam, Ambroise; Toko, Ricardo; Chelo, David; Tekendo-Ngongang, Cedrik; Kingue, Samuel; Dahoun, Sophie

    2017-06-01

    The 22q11.2 deletion syndrome is amongst the most common microdeletion syndrome in humans. Its prevalence remains unknown in sub-Saharan Africa, and its clinical features are under-reported for people of African descent. We have investigated the prevalence of the 22q11.2 deletion syndrome in patients with congenital heart defects in Cameroon. A total of 70 of 100 cases of congenital cardiac malformation with echocardiographic evidence were examined prospectively and tested for the 22q11.2 deletion, using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization. Two of 70 patients (2.8%) were found to have 22q11.2 deletion. Both cases had conotruncal heart defects and exhibited extracardiac features of the 22q11.2 deletion syndrome that were either classical (e.g., puffy upper eyelids, bulbous tip of the nose) or less identifiable (telecanthus, hooding of eyelids and prominent nasal bridge). The report shows that the prevalence of the 22q11.2 deletion syndrome in patients with heart malformations in Cameroon (2.8%) is similar to that of various world populations. The clinical phenotypes will contribute to the Global Atlas for dysmorphology. "Omics" technologies offer much promise in genetic/genomic screening of severe global health problems. Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

  11. Time-based prospective memory in children and adolescents with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Souchay, Céline; Dubourg, Lydia; Ballhausen, Nicola; Schneider, Maude; Cerf, Charline; Schnitzspahn, Katharina; Faivre, Laurence; Kliegel, Matthias; Eliez, Stephan

    2017-11-14

    22q11.2 deletion syndrome, also known as velo-cardio-facial syndrome (VCFS) is a genetic disorder caused by a microdeletion on chromosome 22q11.2 and characterized by marked impairment in visual attention and executive function. The present study examined if this cognitive deficit extends to prospective memory (the type of memory involved in remembering to perform actions in the future). 20 participants with 22q11.2DS aged between 6 and 14 were included in the study as well as 22 typically developing individuals (TDC) aged 6-12. To measure prospective memory, participants were asked to play a driving game (the Dresden Cruiser). This time-based prospective memory task required children to remember to refuel their car when the fuel level was low by pressing a refuel button while driving. Participants with 22q11.2DS remembered less often to refuel the car. Furthermore, participants with 22q11.2DS checked the fuel gage significantly less often than the controls. Participants with 22q11.2DS therefore demonstrate difficulties completing a time-based prospective memory task. This can be explained by a generally less frequent time checking behavior in comparison to TDC.

  12. 16p11.2 Deletion mice display cognitive deficits in touchscreen learning and novelty recognition tasks.

    Science.gov (United States)

    Yang, Mu; Lewis, Freeman C; Sarvi, Michael S; Foley, Gillian M; Crawley, Jacqueline N

    2015-12-01

    Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2+/- mice, confirming previous findings. A similarly robust deficit in object location memory was discovered in +/-, indicating impaired spatial novelty recognition. Generalizability of novelty recognition deficits in +/- mice extended to preference for social novelty. Robust learning deficits and cognitive inflexibility were detected using Bussey-Saksida touchscreen operant chambers. During acquisition of pairwise visual discrimination, +/- mice required significantly more training trials to reach criterion than wild-type littermates (+/+), and made more errors and correction errors than +/+. In the reversal phase, all +/+ reached criterion, whereas most +/- failed to reach criterion by the 30-d cutoff. Contextual and cued fear conditioning were normal in +/-. These cognitive phenotypes may be relevant to some aspects of cognitive impairments in humans with 16p11.2 deletion, and support the use of 16p11.2+/- mice as a model system for discovering treatments for cognitive impairments in 16p11.2 deletion syndrome. © 2015 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Westinghouse-GOTHIC distributed parameter modelling for HDR test E11.2

    International Nuclear Information System (INIS)

    Narula, J.S.; Woodcock, J.

    1994-01-01

    The Westinghouse-GOTHIC (WGOTHIC) code is a sophisticated mathematical computer code designed specifically for the thermal hydraulic analysis of nuclear power plant containment and auxiliary buildings. The code is capable of sophisticated flow analysis via the solution of mass, momentum, and energy conservation equations. Westinghouse has investigated the use of subdivided noding to model the flow patterns of hydrogen following its release into a containment atmosphere. For the investigation, several simple models were constructed to represent a scale similar to the German HDR containment. The calculational models were simplified to test the basic capability of the plume modeling methods to predict stratification while minimizing the number of parameters. A large empty volume was modeled, with the same volume and height as HDR. A scenario was selected that would be expected to stably stratify, and the effects of noding on the prediction of stratification was studied. A single phase hot gas was injected into the volume at a height similar to that of HDR test E11.2, and there were no heat sinks modeled. Helium was released into the calculational models, and the resulting flow patterns were judged relative to the expected results. For each model, only the number of subdivisions within the containment volume was varied. The results of the investigation of noding schemes has provided evidence of the capability of subdivided (distributed parameter) noding. The results also showed that highly inaccurate flow patterns could be obtained by using an insufficient number of subdivided nodes. This presents a significant challenge to the containment analyst, who must weigh the benefits of increased noding with the penalties the noding may incur on computational efficiency. Clearly, however, an incorrect noding choice may yield erroneous results even if great care has been taken in modeling accurately all other characteristics of containments. (author). 9 refs., 9 figs

  14. Default mode network connectivity and reciprocal social behavior in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Schreiner, Matthew J; Karlsgodt, Katherine H; Uddin, Lucina Q; Chow, Carolyn; Congdon, Eliza; Jalbrzikowski, Maria; Bearden, Carrie E

    2014-09-01

    22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and other default mode network (DMN) nodes, including the precuneus, precentral gyrus and left frontal pole. 22q11DS patients did not show age-associated FC changes observed in typically developing controls. Increased connectivity between PCC, medial prefrontal regions and the anterior cingulate cortex, was associated with lower SRS scores (i.e. improved social competence) in 22q11DS. DMN integrity may play a key role in social information processing. We observed disrupted DMN connectivity in 22q11DS, paralleling reports from idiopathic autism and schizophrenia. Increased strength of long-range DMN connectivity was associated with improved social functioning in 22q11DS. These findings support a 'developmental-disconnection' hypothesis of symptom development in this disorder. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Social cognition in 22q11.2 microdeletion syndrome: relevance to psychosis?

    Science.gov (United States)

    Jalbrzikowski, Maria; Carter, Chelsea; Senturk, Damla; Chow, Carolyn; Hopkins, Jessica M; Green, Michael F; Galván, Adriana; Cannon, Tyrone D; Bearden, Carrie E

    2012-12-01

    22q11.2 deletion syndrome (22qDS) represents one of the largest known genetic risk factors for schizophrenia. Approximately 30% of individuals with 22qDS develop psychotic illness in adolescence or young adulthood. Given that deficits in social cognition are increasingly viewed as a central aspect of idiopathic schizophrenia, we sought to investigate abilities in this domain as a predictor of psychotic symptoms in 22qDS participants. We assessed multiple domains of social and non-social cognition in 22qDS youth to: 1) characterize performance across these domains in 22qDS, and identify whether 22qDS participants fail to show expected patterns of age-related improvements on these tasks; and 2) determine whether social cognition better predicts positive and negative symptoms than does non-social cognition. Task domains assessed were: emotion recognition and differentiation, Theory of Mind (ToM), verbal knowledge, visuospatial skills, working memory, and processing speed. Positive and negative symptoms were measured using scores obtained from the Structured Interview for Prodromal Symptoms (SIPS). 22qDS participants (N=31, mean age: 15.9) showed the largest impairment, relative to healthy controls (N=31, mean age: 15.6), on measures of ToM and processing speed. In contrast to controls, 22qDS participants did not show age-related improvements on measures of working memory and verbal knowledge. Notably, ToM performance was the best predictor of positive symptoms in 22qDS, accounting for 39% of the variance in symptom severity. Processing speed emerged as the best predictor of negative symptoms, accounting for 37% of the variance in symptoms. Given that ToM was a robust predictor of positive symptoms in our sample, these findings suggest that social cognition may be a valuable intermediate trait for predicting the development of psychosis. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Hippocampal malrotation is associated with chromosome 22q11.2 microdeletion.

    Science.gov (United States)

    Andrade, Danielle M; Krings, Timo; Chow, Eva W C; Kiehl, Tim-Rasmus; Bassett, Anne S

    2013-09-01

    Patients with chromosome 22q11.2 deletion syndrome (22q11DS) are at a seven fold increased risk of developing seizures. However, only a fraction of these patients exhibit structural abnormalities such as polymicrogyria (PMG) and periventricular nodular heterotopia (PNH) that are known to cause seizures and to be associated with 22q11DS. In this study we used a dedicated seizure imaging protocol to look for additional structural abnormalities in these individuals that may explain the elevated risk of seizure disorder in this patient group. Nineteen consecutive adult subjects with 22q11DS underwent a 3 Tesla MRI with a dedicated high-resolution seizure protocol. Neurological exam was performed in all patients. Genome-wide analysis excluded the presence of other pathogenic microdeletions or duplications. Structural abnormalities were found in 11 of 14 subjects with sufficient image quality. These included three patients with PNH, one of whom had associated PMG. In addition, there was a surprisingly high prevalence of unilateral hippocampal malrotation (HIMAL), observed in 9 of 14 cases (64%). EEG findings showed interictal epileptiform discharges with focal distribution in four patients and generalized discharges in one patient. The results suggest that, in addition to other known structural abnormalities, 22q11DS is associated with HIMAL. It has been suggested that this developmental abnormality of the hippocampus may predispose or otherwise contribute to epileptogenesis. However in this study we observed HIMAL in a large proportion of patients, with and without epilepsy. Therefore, other as yet unknown factors may contribute to the high prevalence of epilepsy in this population.

  17. Hearing loss in a mouse model of 22q11.2 Deletion Syndrome.

    Directory of Open Access Journals (Sweden)

    Jennifer C Fuchs

    Full Text Available 22q11.2 Deletion Syndrome (22q11DS arises from an interstitial chromosomal microdeletion encompassing at least 30 genes. This disorder is one of the most significant known cytogenetic risk factors for schizophrenia, and can also cause heart abnormalities, cognitive deficits, hearing difficulties, and a variety of other medical problems. The Df1/+ hemizygous knockout mouse, a model for human 22q11DS, recapitulates many of the deficits observed in the human syndrome including heart defects, impaired memory, and abnormal auditory sensorimotor gating. Here we show that Df1/+ mice, like human 22q11DS patients, have substantial rates of hearing loss arising from chronic middle ear infection. Auditory brainstem response (ABR measurements revealed significant elevation of click-response thresholds in 48% of Df1/+ mice, often in only one ear. Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities, but frequent signs of otitis media (OM, chronic inflammation of the middle ear, including excessive effusion and thickened mucosa. In mice for which both in vivo ABR thresholds and post mortem middle-ear histology were obtained, the severity of signs of OM correlated directly with the level of hearing impairment. These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22q11DS could arise from abnormalities in auditory processing. Furthermore, the findings indicate that Df1/+ mice are an excellent model for increased risk of OM in human 22q11DS patients. Given the frequently monaural nature of OM in Df1/+ mice, these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM.

  18. Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2).

    Science.gov (United States)

    Gropman, Andrea L; Duncan, Wallace C; Smith, Ann C M

    2006-05-01

    The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring, mental retardation and multiple congenital anomalies caused by a heterozygous interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis syndrome is characterized by a distinct pattern of features including infantile hypotonia, generalized complacency and lethargy in infancy, minor skeletal (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities, middle ear and laryngeal abnormalities including hoarse voice, as well as marked early expressive speech and language delays, psychomotor and growth retardation, and a 24-hour sleep disturbance. A striking neurobehavioral pattern of stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive and self-injurious and aggressive behavior is observed with increasing age. The diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a constellation of physical, developmental, and behavioral features in combination with a sleep disorder characterized by inverted circadian rhythm of melatonin secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy and early childhood, and become more recognizable with advancing age. Infants are described as looking "cherubic" with a Down syndrome-like appearance, whereas with age the facial appearance is that of relative prognathism. Early diagnosis requires awareness of the often subtle clinical and neurobehavioral phenotype of the infant period. Speech delay with or without hearing loss is common. Most children are diagnosed in mid-childhood when the features of the disorder are most recognizable and striking. While improvements in cytogenetic analysis help to bring cases to clinical recognition at an earlier age, this review seeks to increase clinical awareness about Smith-Magenis syndrome by presenting the salient features observed at different ages including descriptions of the neurologic and behavioral

  19. Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

    Energy Technology Data Exchange (ETDEWEB)

    Grassi, Marcília S., E-mail: marcilia.grassi@hc.fm.usp.br; Jacob, Cristina M. A. [Instituto da Criança - HC-FMUSP, São Paulo, SP (Brazil); Kulikowski, Leslie D. [Departamento de Patologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil); Pastorino, Antonio C. [Instituto da Criança - HC-FMUSP, São Paulo, SP (Brazil); Dutra, Roberta L. [Departamento de Patologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil); Miura, Nana; Jatene, Marcelo B. [Instituto do Coração - HC-FMUSP, São Paulo, SP (Brazil); Pegler, Stephanie P.; Kim, Chong A.; Carneiro-Sampaio, Magda [Instituto da Criança - HC-FMUSP, São Paulo, SP (Brazil)

    2014-11-15

    To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.

  20. Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Bassett, Anne S; Lowther, Chelsea; Merico, Daniele; Costain, Gregory; Chow, Eva W C; van Amelsvoort, Therese; McDonald-McGinn, Donna; Gur, Raquel E; Swillen, Ann; Van den Bree, Marianne; Murphy, Kieran; Gothelf, Doron; Bearden, Carrie E; Eliez, Stephan; Kates, Wendy; Philip, Nicole; Sashi, Vandana; Campbell, Linda; Vorstman, Jacob; Cubells, Joseph; Repetto, Gabriela M; Simon, Tony; Boot, Erik; Heung, Tracy; Evers, Rens; Vingerhoets, Claudia; van Duin, Esther; Zackai, Elaine; Vergaelen, Elfi; Devriendt, Koen; Vermeesch, Joris R; Owen, Michael; Murphy, Clodagh; Michaelovosky, Elena; Kushan, Leila; Schneider, Maude; Fremont, Wanda; Busa, Tiffany; Hooper, Stephen; McCabe, Kathryn; Duijff, Sasja; Isaev, Karin; Pellecchia, Giovanna; Wei, John; Gazzellone, Matthew J; Scherer, Stephen W; Emanuel, Beverly S; Guo, Tingwei; Morrow, Bernice E; Marshall, Christian R

    2017-11-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression. Through an international consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), the authors compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: a schizophrenia group and those with no psychotic disorder at age ≥25 years. The authors assessed whether genes overlapped by rare CNVs were overrepresented in functional pathways relevant to schizophrenia. Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a stepwise logistic regression model and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had, on average, more genes overlapped. The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci. The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia.

  1. Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

    Directory of Open Access Journals (Sweden)

    Marcília S. Grassi

    2014-11-01

    Full Text Available Background: To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS in patients with congenital heart disease (CHD. Objective: To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods: The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18 and/or MLPA (n = 42, in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results: CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%. Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60% and/or elongated nose (53.3%, narrow palpebral fissure (50%, dysplastic, overfolded ears (48.3%, thin lips (41.6%, elongated fingers (38.3% and short stature (36.6%. Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM in two other patients. Conclusion: Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.

  2. Whole-genome sequencing suggests mechanisms for 22q11.2 deletion-associated Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Nancy J Butcher

    Full Text Available To investigate disease risk mechanisms of early-onset Parkinson's disease (PD associated with the recurrent 22q11.2 deletion, a genetic risk factor for early-onset PD.In a proof-of-principle study, we used whole-genome sequencing (WGS to investigate sequence variants in nine adults with 22q11.2DS, three with neuropathologically confirmed early-onset PD and six without PD. Adopting an approach used recently to study schizophrenia in 22q11.2DS, here we tested candidate gene-sets relevant to PD.No mutations common to the cases with PD were found in the intact 22q11.2 region. While all were negative for rare mutations in a gene-set comprising PD disease-causing and risk genes, another candidate gene-set of 1000 genes functionally relevant to PD presented a nominally significant (P = 0.03 enrichment of rare putatively damaging missense variants in the PD cases. Polygenic score results, based on common variants associated with PD risk, were non-significantly greater in those with PD.The results of this first-ever pilot study of WGS in PD suggest that the cumulative burden of genome-wide sequence variants may contribute to expression of early-onset PD in the presence of threshold-lowering dosage effects of a 22q11.2 deletion. We found no evidence that expression of PD in 22q11.2DS is mediated by a recessive locus on the intact 22q11.2 chromosome or mutations in known PD genes. These findings offer initial evidence of the potential effects of multiple within-individual rare variants on the expression of PD and the utility of next generation sequencing for studying the etiology of PD.

  3. Whole-genome sequencing suggests mechanisms for 22q11.2 deletion-associated Parkinson's disease.

    Science.gov (United States)

    Butcher, Nancy J; Merico, Daniele; Zarrei, Mehdi; Ogura, Lucas; Marshall, Christian R; Chow, Eva W C; Lang, Anthony E; Scherer, Stephen W; Bassett, Anne S

    2017-01-01

    To investigate disease risk mechanisms of early-onset Parkinson's disease (PD) associated with the recurrent 22q11.2 deletion, a genetic risk factor for early-onset PD. In a proof-of-principle study, we used whole-genome sequencing (WGS) to investigate sequence variants in nine adults with 22q11.2DS, three with neuropathologically confirmed early-onset PD and six without PD. Adopting an approach used recently to study schizophrenia in 22q11.2DS, here we tested candidate gene-sets relevant to PD. No mutations common to the cases with PD were found in the intact 22q11.2 region. While all were negative for rare mutations in a gene-set comprising PD disease-causing and risk genes, another candidate gene-set of 1000 genes functionally relevant to PD presented a nominally significant (P = 0.03) enrichment of rare putatively damaging missense variants in the PD cases. Polygenic score results, based on common variants associated with PD risk, were non-significantly greater in those with PD. The results of this first-ever pilot study of WGS in PD suggest that the cumulative burden of genome-wide sequence variants may contribute to expression of early-onset PD in the presence of threshold-lowering dosage effects of a 22q11.2 deletion. We found no evidence that expression of PD in 22q11.2DS is mediated by a recessive locus on the intact 22q11.2 chromosome or mutations in known PD genes. These findings offer initial evidence of the potential effects of multiple within-individual rare variants on the expression of PD and the utility of next generation sequencing for studying the etiology of PD.

  4. Whole-genome sequencing suggests mechanisms for 22q11.2 deletion-associated Parkinson’s disease

    Science.gov (United States)

    Butcher, Nancy J.; Merico, Daniele; Zarrei, Mehdi; Ogura, Lucas; Marshall, Christian R.; Chow, Eva W. C.; Lang, Anthony E.; Scherer, Stephen W.; Bassett, Anne S.

    2017-01-01

    Objectives To investigate disease risk mechanisms of early-onset Parkinson’s disease (PD) associated with the recurrent 22q11.2 deletion, a genetic risk factor for early-onset PD. Methods In a proof-of-principle study, we used whole-genome sequencing (WGS) to investigate sequence variants in nine adults with 22q11.2DS, three with neuropathologically confirmed early-onset PD and six without PD. Adopting an approach used recently to study schizophrenia in 22q11.2DS, here we tested candidate gene-sets relevant to PD. Results No mutations common to the cases with PD were found in the intact 22q11.2 region. While all were negative for rare mutations in a gene-set comprising PD disease-causing and risk genes, another candidate gene-set of 1000 genes functionally relevant to PD presented a nominally significant (P = 0.03) enrichment of rare putatively damaging missense variants in the PD cases. Polygenic score results, based on common variants associated with PD risk, were non-significantly greater in those with PD. Conclusions The results of this first-ever pilot study of WGS in PD suggest that the cumulative burden of genome-wide sequence variants may contribute to expression of early-onset PD in the presence of threshold-lowering dosage effects of a 22q11.2 deletion. We found no evidence that expression of PD in 22q11.2DS is mediated by a recessive locus on the intact 22q11.2 chromosome or mutations in known PD genes. These findings offer initial evidence of the potential effects of multiple within-individual rare variants on the expression of PD and the utility of next generation sequencing for studying the etiology of PD. PMID:28430790

  5. Diagnostic Approach to Microdeletion Syndromes Based on 22q11.2 Investigation: Challenges in Four Cases.

    Science.gov (United States)

    Sgardioli, Ilária C; de Mello Copelli, Matheus; Monteiro, Fabíola P; Dos Santos, Ana P; Lustosa Mendes, Elaine; Paiva Vieira, Társis; Gil-da-Silva-Lopes, Vera L

    2017-08-01

    In the last few decades, different methods for the detection of genomic imbalances, such as the microdeletion syndromes, were developed. The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome and presents wide clinical heterogeneity. The aim of this study was to describe 4 unusual cases of genomic imbalances found in individuals with suspected microdeletion syndromes. Different methods were necessary to complete the diagnosis and to obtain information for genetic counseling. The study was retrospective and descriptive. From August 2014 to December 2015, 39 individuals were assessed using FISH and/or MLPA; in 15 cases, chromosomal microarray (CMA) analysis was carried out. Of 39 registered individuals, we found deletions in the 22q11.2 region in 10 individuals (8 individuals with 22q11.2DS and 2 individuals presenting with atypical deletions in the 22q11.2 region: 1 distal deletion and 1 central deletion). In one case with a typical 22q11.2 deletion, a familial balanced translocation was detected. In another case without a 22q11.2 deletion, a 6p duplication concomitant with a 9p deletion was detected by CMA. Clinical data are reported and diagnostic investigations are discussed. Essential aspects for the understanding of different diagnostic techniques of genomic imbalances are considered, and the 4 cases described underline the complexity and the difficulties involved in the diagnostic process. The approach is informative for clinical practice and may be applied in other contexts of genomic imbalance investigation in microdeletion syndromes.

  6. 22q11.2 Deletion Syndrome: Laboratory Diagnosis and TBX1 and FGF8 Mutation Screening

    Science.gov (United States)

    Sgardioli, Ilária C.; Vieira, Társis P.; Simioni, Milena; Monteiro, Fabíola P.; Gil-da-Silva-Lopes, Vera L.

    2015-01-01

    Velocardiofacial syndrome is one of the recognized forms of chromosome 22q11.2 deletion syndrome (22q11.2 DS) and has an incidence of 1 of 4,000 to 1 of 6,000 births. Nevertheless, the 22q11 deletion is not found in several patients with a 22q11.2 DS phenotype. In this situation, other chromosomal aberrations and/or mutations in the T-box 1 transcription factor C (TBX1) gene have been detected in some patients. A similar phenotype to that of the 22q11.2 DS has been reported in animal models with mutations in fibroblast growth factor 8 (Fgf8) gene. To date, FGF8 mutations have not been investigated in humans. We tested a strategy to perform laboratory testing to reduce costs in the investigation of patients presenting with the 22q11.2 DS phenotype. A total of 109 individuals with clinical suspicion were investigated using GTG-banding karyotype, fluorescence in situ hybridization, and/or multiplex ligation-dependent probe amplification. A conclusive diagnosis was achieved in 33 of 109 (30.2%) cases. In addition, mutations in the coding regions of TBX1 and FGF8 genes were investigated in selected cases where 22q11.2 deletion had been excluded, and no pathogenic mutations were detected in both genes. This study presents a strategy for molecular genetic characterization of patients presenting with the 22q11.2 DS using different laboratory techniques. This strategy could be useful in different countries, according to local resources. Also, to our knowledge, this is the first investigation of FGF8 gene in humans with this clinical suspicion. PMID:27617111

  7. Dr. Hans Chang, Director, Physics Research Committee, Stichting voor Fundamenteel Onderzoek der Materie (FOM), Dr. Joris Van Enst, Head of Science Policy Division, Ministry of Education, Culture and S cience, Dr. Jan Bezemer, NL Delegate CERN, Netherlands

    CERN Multimedia

    Patrice Loiez

    1999-01-01

    Dr. Hans Chang, Director, Physics Research Committee, Stichting voor Fundamenteel Onderzoek der Materie (FOM), Dr. Joris Van Enst, Head of Science Policy Division, Ministry of Education, Culture and S cience, Dr. Jan Bezemer, NL Delegate CERN, Netherlands

  8. Deleción 22q11.2 en pacientes con defecto cardiaco conotruncal y fenotipo del síndrome de la deleción 22q11.2

    OpenAIRE

    Belangero, Sintia Iole [UNIFESP; Bellucco, Fernanda Teixeira da Silva [UNIFESP; Kulikowski, Leslie Domenici [UNIFESP; Christofolini, Denise Maria [UNIFESP; Cernach, Mirlene Cecilia Soares Pinho [UNIFESP; Melaragno, Maria Isabel [UNIFESP

    2009-01-01

    FUNDAMENTO: A síndrome da deleção 22q11.2 é a mais freqüente síndrome de microdeleção humana. O fenótipo é altamente variável e caracterizado por defeito cardíaco conotruncal, dismorfias faciais, insuficiência velofaríngea, dificuldade de aprendizagem e retardo mental. OBJETIVO: O objetivo deste trabalho foi investigar a freqüência da deleção 22q11.2 em uma amostra brasileira de indivíduos portadores de cardiopatia conontrucal isolada e do fenótipo da síndrome da deleção 22q11.2. MÉTODOS: Vin...

  9. Neutralization of X4- and R5-tropic HIV-1 NL4-3 variants by HOCl-modified serum albumins

    Directory of Open Access Journals (Sweden)

    Schwalbe Birco

    2010-06-01

    Full Text Available Abstract Background Myeloperoxidase (MPO, an important element of the microbicidal activity of neutrophils, generates hypochlorous acid (HOCl from H2O2 and chloride, which is released into body fluids. Besides its direct microbicidal activity, HOCl can react with amino acid residues and HOCl-modified proteins can be detected in vivo. Findings This report is based on binding studies of HOCl-modified serum albumins to HIV-1 gp120 and three different neutralization assays using infectious virus. The binding studies were carried out by surface plasmon resonance spectroscopy and by standard ELISA techniques. Virus neutralization assays were carried out using HIV-1 NL4-3 virus and recombinant strains with CXCR4 and CCR5 coreceptor usage. Viral infection was monitored by a standard p24 or X-gal staining assay. Our data demonstrate that HOCl-modified mouse-, bovine- and human serum albumins all bind to the HIV-1 NL4-3 gp120 (LAV glycoprotein in contrast to non-modified albumin. Binding of HOCl-modified albumin to gp120 correlated to the blockade of CD4 as well as that of V3 loop specific monoclonal antibody binding. In neutralization experiments, HOCl-modified serum albumins inhibited replication and syncytium formation of the X4- and R5-tropic NL4-3 isolates in a dose dependent manner. Conclusions Our data indicate that HOCl-modified serum albumin veils the binding site for CD4 and the V3 loop on gp120. Such masking of the viral gp120/gp41 envelope complex might be a simple but promising strategy to inactivate HIV-1 and therefore prevent infection when HOCl-modified serum albumin is applied, for example, as a topical microbicide.

  10. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies

    Science.gov (United States)

    de Kovel, Carolien G. F.; Trucks, Holger; Helbig, Ingo; Mefford, Heather C.; Baker, Carl; Leu, Costin; Kluck, Christian; Muhle, Hiltrud; von Spiczak, Sarah; Ostertag, Philipp; Obermeier, Tanja; Kleefuß-Lie, Ailing A.; Hallmann, Kerstin; Steffens, Michael; Gaus, Verena; Klein, Karl M.; Hamer, Hajo M.; Rosenow, Felix; Brilstra, Eva H.; Kasteleijn-Nolst Trenité, Dorothée; Swinkels, Marielle E. M.; Weber, Yvonne G.; Unterberger, Iris; Zimprich, Fritz; Urak, Lydia; Feucht, Martha; Fuchs, Karoline; Møller, Rikke S.; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Rückert, Ina-Maria; Wichmann, Heinz-Erich; Franke, Andre; Schreiber, Stefan; Nürnberg, Peter; Elger, Christian E.; Lerche, Holger; Stephani, Ulrich; Koeleman, Bobby P. C.; Lindhout, Dick; Eichler, Evan E.

    2010-01-01

    Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic risk factor for common idiopathic generalized epilepsy syndromes, implicating that other recurrent microdeletions may also be involved in epileptogenesis. This study aimed to investigate the impact of five microdeletions at the genomic hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic risk to common idiopathic generalized epilepsy syndromes. The candidate microdeletions were assessed by high-density single nucleotide polymorphism arrays in 1234 patients with idiopathic generalized epilepsy from North-western Europe and 3022 controls from the German population. Microdeletions were validated by quantitative polymerase chain reaction and their breakpoints refined by array comparative genomic hybridization. In total, 22 patients with idiopathic generalized epilepsy (1.8%) carried one of the five novel microdeletions compared with nine controls (0.3%) (odds ratio = 6.1; 95% confidence interval 2.8–13.2; χ2 = 26.7; 1 degree of freedom; P = 2.4 × 10−7). Microdeletions were observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2 (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and 22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the microdeletions at 15q11.2 (odds ratio = 4.9; 95% confidence interval 1.8–13.2; P = 4.2 × 10−4) and 16p13.11 (odds ratio = 7.4; 95% confidence interval 1.3–74.7; P = 0.009). Including nine

  11. The clinical presentation of attention deficit-hyperactivity disorder (ADHD) in children with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Niarchou, Maria; Martin, Joanna; Thapar, Anita; Owen, Michael J; van den Bree, Marianne B M

    2015-12-01

    Although attention deficit-hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children with 22q11.2DS, it remains unclear whether its clinical presentation is similar to that in children with idiopathic ADHD. The aim of this study is to compare the ADHD phenotype in children with and without 22q11.2DS by examining ADHD symptom scores, patterns of psychiatric comorbidity, IQ and gender distribution. Forty-four children with 22q11.2DS and ADHD (mean age = 9.6), 600 clinic children (mean age = 10.8) and 77 children with ADHD from a population cohort (mean age = 10.8) participated in the study. Psychopathology was assessed using parent-report research diagnostic instruments. There was a higher proportion of females in the 22q11.2DS ADHD sample in relation to the clinical sample (χ(2)  = 18.2, P ADHD inattentive subtype (χ(2)  = 114.76, P hyperactive-impulsive symptoms compared to the clinical group (z = 8.43, P ADHD group parents reported fewer oppositional defiant disorder/conduct disorder symptoms (z = 6.33, P disorder (χ(2)  = 4.56, P = 0.03) in relation to the clinical group. Two percent of the 22q11.2 DS ADHD sample had received ADHD treatment. The results were similar when the 22q11.2 ADHD group was compared to the population cohort ADHD group. The clinical presentation of ADHD and patterns of co-morbidity in 22q11.2DS is different from that in idiopathic ADHD. This could lead to clinical under-recognition of ADHD in this group. Examining psychopathology in 22q11.2DS can provide insights into the genetic origins of psychiatric problems with implications beyond the 22q11.2DS population. © 2015 Wiley Periodicals, Inc.

  12. Kur’an’a Göre Üstünlük Duygusunun Düşünce ve Davranışlara Etkileri

    Directory of Open Access Journals (Sweden)

    Harun Savut

    2015-06-01

    Full Text Available Üstünlük duygusu insanın tüm davranışlarını etkisi altına alan, düşünce ve davranışlarda sapmalara sebep olan bir tavırdır. Doğruyu kendisini merkeze koyarak değerlendiren insanın tüm kutsalı yine kendisi olur. Şayet çevredekiler bu kutsalı onaylarsa kabul edilir ve değer görürler. Aksinin söz konusu olduğu durumlarda ise karşı durulması gereken düşman şeklinde algılanırlar. Bu ise akli melekelerin önünde set oluşturan, doğru düşünmeyi negatif yönde etkileyen, bu sebeple de yanlışları tetikleyen bir durumdur. Bunun neticesinde hakkın kabulü zorlaşır, hatta imkansız bir hal alır. İnsanı kendi algısı ile çelişen gerçekleri, doğruları inkara sürükler. Benlik kaynaklı bu savrulma küfür ve şirkin kapılarını açar. Bu makalede üstünlük hissinin yol açtığı algı ve düşünme hatalarıyla tebarüz eden kişilerin düşüncelerinde ortaya çıkan savrulmalar, yanılsamalar analiz edilmiştir. Üstünlük algısının gerekçelendirilmesinde kişi veya toplumun sahip olduğu imkanların rolü değerlendirilmiştir. Üstünlük hissinin neden olduğu tahammülsüzlük ve algı kapanması üzerinde durulmuştur.

  13. 22q11.2 deletion status and disease burden in children and adolescents with tetralogy of Fallot.

    Science.gov (United States)

    Mercer-Rosa, Laura; Paridon, Stephen M; Fogel, Mark A; Rychik, Jack; Tanel, Ronn E; Zhao, Huaqing; Zhang, Xuemei; Yang, Wei; Shults, Justine; Goldmuntz, Elizabeth

    2015-02-01

    Patients with repaired tetralogy of Fallot experience variable outcomes for reasons that are incompletely understood. We hypothesize that genetic variants contribute to this variability. We sought to investigate the association of 22q11.2 deletion status with clinical outcome in patients with repaired tetralogy of Fallot. We performed a cross-sectional study of tetralogy of Fallot subjects who were tested for 22q11.2 deletion, and underwent cardiac magnetic resonance, exercise stress test, and review of medical history. We studied 165 subjects (12.3±3.1 years), of which 30 (18%) had 22q11.2 deletion syndrome (22q11.2DS). Overall, by cardiac magnetic resonance the right ventricular ejection fraction was 60±8%, pulmonary regurgitant fraction was 34±17%, and right ventricular end-diastolic volume was 114±39 cc/m(2). On exercise stress test, maximum oxygen consumption was 76±16% predicted. Despite comparable right ventricular function and pulmonary regurgitant fraction, on exercise stress test the 22q11.2DS had significantly lower percent predicted: forced vital capacity (61.5±16 versus 80.5±14; Ptetralogy of Fallot. These findings may provide avenues for intervention to improve outcomes, and should be re-evaluated longitudinally because these associations may become more pronounced with time. © 2015 American Heart Association, Inc.

  14. A highly penetrant form of childhood apraxia of speech due to deletion of 16p11.2.

    Science.gov (United States)

    Fedorenko, Evelina; Morgan, Angela; Murray, Elizabeth; Cardinaux, Annie; Mei, Cristina; Tager-Flusberg, Helen; Fisher, Simon E; Kanwisher, Nancy

    2016-02-01

    Individuals with heterozygous 16p11.2 deletions reportedly suffer from a variety of difficulties with speech and language. Indeed, recent copy-number variant screens of children with childhood apraxia of speech (CAS), a specific and rare motor speech disorder, have identified three unrelated individuals with 16p11.2 deletions. However, the nature and prevalence of speech and language disorders in general, and CAS in particular, is unknown for individuals with 16p11.2 deletions. Here we took a genotype-first approach, conducting detailed and systematic characterization of speech abilities in a group of 11 unrelated children ascertained on the basis of 16p11.2 deletions. To obtain the most precise and replicable phenotyping, we included tasks that are highly diagnostic for CAS, and we tested children under the age of 18 years, an age group where CAS has been best characterized. Two individuals were largely nonverbal, preventing detailed speech analysis, whereas the remaining nine met the standard accepted diagnostic criteria for CAS. These results link 16p11.2 deletions to a highly penetrant form of CAS. Our findings underline the need for further precise characterization of speech and language profiles in larger groups of affected individuals, which will also enhance our understanding of how genetic pathways contribute to human communication disorders.

  15. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome

    Science.gov (United States)

    de la Morena, M. Teresa; Eitson, Jennifer L.; Dozmorov, Igor M.; Belkaya, Serkan; Hoover, Ashley R.; Anguiano, Esperanza; Pascual, M. Virginia; van Oers, Nicolai S.C.

    2013-01-01

    Patients with 22q11.2 deletion syndrome have heterogeneous clinical presentations including immunodeficiency, cardiac anomalies, and hypocalcemia. The syndrome arises from hemizygous deletions of up to 3 Mb on chromosome 22q11.2, a region that contains 60 genes and 4 microRNAs. MicroRNAs are important post-transcriptional regulators of gene expression, with mutations in several microRNAs causal to specific human diseases. We characterized the microRNA expression patterns in the peripheral blood of patients with 22q11.2 deletion syndrome (n=31) compared to normal controls (n=22). Eighteen microRNAs had a statistically significant differential expression (p22q11.2 deletion syndrome cohort exhibited microRNA expression hyper-variability and group dysregulation. Selected microRNAs distinguished patients with cardiac anomalies, hypocalcemia, and/or low circulating T cell counts. In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance. PMID:23454892

  16. Adults with 22q11.2 deletion syndrome have a different velopharyngeal anatomy with predisposition to velopharyngeal insufficiency.

    Science.gov (United States)

    Filip, Charles; Impieri, Davide; Aagenæs, Ingegerd; Breugem, Corstiaan; Høgevold, Hans Erik; Særvold, Tone; Aukner, Ragnhild; Lima, Kari; Tønseth, Kim; Abrahamsen, Tore G

    2018-04-01

    To find out if subjects with 22q11.2 deletion syndrome (DS) have a different velopharyngeal anatomy which could cause velopharyngeal insufficiency (VPI). A prospective study of 16 subjects >16 years of age with 22q11.2 DS, without overt cleft palate and without previous VPI surgery, and 48 healthy controls >18 years of age were included in the study. Speech was recorded and scored blindly by two independent senior speech therapists. All 64 individuals had MRI scans, which were analyzed blindly by a consultant radiologist. Subjects with 22q11.2 DS had a mild degree of weak pressure consonants (mean score); borderline to mild degree of hypernasality and audible nasal emission (mean score). All controls had normal speech. When comparing subjects (22q11.2 DS) to controls, we found the subjects to have the following: A shorter distance between left and right points of origin of the levator veli palatini muscle (LVP) (p 22q11.2 DS showed a different velopharyngeal anatomy, which will make these individuals more prone to VPI. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Use of amniocytes for prenatal diagnosis of 22q11.2 microdeletion syndrome: a feasibility study.

    Science.gov (United States)

    Liu, Tao; Liu, Qing; Wang, Yi-xin; Yang, Dong; Xin, Yi; Fang, Zhen; Ding, Shu-fang; Yang, Jie-fu

    2010-02-20

    A study of prenatal genetic diagnosis for 22q11.2 microdeletion, which has a wide phenotypic spectrum that involves almost all organs, is rarely reported in China. This study aimed to explore the prevalence of 22q11.2 microdeletion in congenitally malformed fetuses via the fluorescent in situ hybridization (FISH) technique and to investigate the feasibility of use of amniocytes to diagnose 22q11.2 microdeletion syndrome prenatally. The study enrolled 23 cases of fetal cardiac malformation, as indicated by ultrasound in Beijing Anzhen Hospital and 14 cases of non-cardiac malformation, as determined by type-B ultrasound in Beijing Anzhen Hospital and other hospitals. Amniotic fluid was obtained by amniocentesis before odinopoeia, and the stillborn fetuses of the induced labor were preceded to autopsy. The amniotic fluid of 20 cesarean deliveries during the same period of time was used as a control. The TUPLE1 gene in the amniotic fluid of malformed and normal fetuses was assessed by the FISH method. The prevalence rates of the TUPLE1 gene deletion in the amniotic fluid cells from fetuses with cardiac deformations and fetuses without such malformations were 43.5% and 57.1%, respectively. The deletion of TUPLE1 was significantly associated with fetal malformation. Chromosome 22q11.2 microdeletion is one of the major factors leading to fetal congenital malformations, and prenatal FISH screening for 22q11.2 microdeletion syndrome is technically feasible using amniocytes.

  18. Further phenotypic expansion of 15q11.2 BP1-BP2 microdeletion (Burnside-Butler) syndrome.

    Science.gov (United States)

    Jerkovich, Adria M; Butler, Merlin G

    2014-01-01

    We report a 10-year-old Caucasian male identified with copy number variation detected by microarray analysis including a maternally inherited 15q11.2 microdeletion involving 4 genes, paternally inherited 13q12.2 microdeletion with 10 genes, and a de novo 2q14.3 duplication involving 4 genes. He had a history of speech delay, cognitive deficits, attention deficit hyperactivity disorder and a posterior lenticonus cataract removed at 5 yr of age. The genes on chromosomes 2 and 13 are not known to be involved with cataract formation, which lends further support of the role of the 15q11.2 region and additional evidence for phenotypic expansion of the 15q11.2 BP1-BP2 microdeletion (termed Burnside-Butler) syndrome.

  19. Atypical autism in a boy with double duplication of 22q11.2: implications of increasing dosage.

    Science.gov (United States)

    Dale, Breanne; Modi, Bonnie MacKinnon; Jilderda, Sanne; McConnell, Beth; Hoang, Ny; Swaroop, Pooja; Falcon, Jhoan; Thiruvahindrapuram, Bhooma; Walker, Susan; Scherer, Stephen W; Stavropoulos, D James; Drmic, Irene E; Carter, Melissa T

    2017-01-01

    Duplication of chromosome 22q11.2 (LCR A-D) has been reported at higher frequencies in clinical samples than the general population, but phenotypes vary widely. Triplication (4 copies) is rare, but studying the associated phenotype may provide insight into dosage-sensitivity of the genes in this chromosomal interval. We describe a proband with a triplication, specifically a "double duplication" (two copies per chromosome) of the 22q11.2 region, while his parents and two siblings each have a single duplication (3 copies). The proband had a heart malformation, dysmorphic features, and learning and socialization deficits, whereas the other family members did not. This family illustrates that while duplication of the 22q11.2 may not be sufficient to cause clinically significant neurodevelopmental or health-related phenotypes, triplication of the same region may result in a phenotype characterized by a mild neurodevelopmental disorder, facial dysmorphism, and possibly cardiac anomalies.

  20. 22q11.2 Deletion Syndrome Is Associated With Impaired Auditory Steady-State Gamma Response.

    Science.gov (United States)

    Larsen, Kit Melissa; Pellegrino, Giovanni; Birknow, Michelle Rosgaard; Kjær, Trine Nørgaard; Baaré, William Frans Christiaan; Didriksen, Michael; Olsen, Line; Werge, Thomas; Mørup, Morten; Siebner, Hartwig Roman

    2018-02-15

    The 22q11.2 deletion syndrome confers a markedly increased risk for schizophrenia. 22q11.2 deletion carriers without manifest psychotic disorder offer the possibility to identify functional abnormalities that precede clinical onset. Since schizophrenia is associated with a reduced cortical gamma response to auditory stimulation at 40 Hz, we hypothesized that the 40 Hz auditory steady-state response (ASSR) may be attenuated in nonpsychotic individuals with a 22q11.2 deletion. Eighteen young nonpsychotic 22q11.2 deletion carriers and a control group of 27 noncarriers with comparable age range (12-25 years) and sex ratio underwent 128-channel EEG. We recorded the cortical ASSR to a 40 Hz train of clicks, given either at a regular inter-stimulus interval of 25 ms or at irregular intervals jittered between 11 and 37 ms. Healthy noncarriers expressed a stable ASSR to regular but not in the irregular 40 Hz click stimulation. Both gamma power and inter-trial phase coherence of the ASSR were markedly reduced in the 22q11.2 deletion group. The ability to phase lock cortical gamma activity to regular auditory 40 Hz stimulation correlated with the individual expression of negative symptoms in deletion carriers (ρ = -0.487, P = .041). Nonpsychotic 22q11.2 deletion carriers lack efficient phase locking of evoked gamma activity to regular 40 Hz auditory stimulation. This abnormality indicates a dysfunction of fast intracortical oscillatory processing in the gamma-band. Since ASSR was attenuated in nonpsychotic deletion carriers, ASSR deficiency may constitute a premorbid risk marker of schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  1. [Chromosome 22q11.2 microdeletion and phenotype analysis of patients with non-syndromic tetralogy of Fallot].

    Science.gov (United States)

    Zhang, Ze-wei; Deng, Jian-ying; Ying, Li-yang; Gao, Zhan; Jin, Jie; Qi, Jian-chuan; Tan, Zheng

    2011-12-01

    To investigate the frequency and clinical phenotypes of 22q11.2 microdeletion in patients with non-syndromic tetralogy of Fallot (TOF). Six-eight non-syndromic TOF patients (38 males and 30 females, aged 0-11 years) were selected and evaluated by history, physical examination and review of medical records. After informed consent was obtained, peripheral blood was drawn for genomic DNA extraction. Chromosome 22q11.2 microdeletion was screened by multiplex ligation-dependent probe amplification (MLPA). Suspected cases were confirmed with fluorescence in situ hybridization (FISH). Data was analyzed with SPSS 11.5 software. Phenotype-genotype correlations were assessed using Fisher's exact test. P values less than 0.05 on a 2-sided test were considered to be significant. Six-eight non-syndromic TOF children were screened for a 22q11.2 deletion, among which 59 (86.8%) presented pulmonary stenosis (PS) and 9 (13.2%) presented pulmonary atresia (PA). Seven patients (10.3%) were found to have carried a deletion. Among these, four had TOF-PS, three had TOF-PA. The frequency of 22q11.2 deletion in patients with TOF-PA (3/9, 33.3%) is much higher than that of TOF-PS (4/59, 6.80%) (P22q11.2 microdeletion is present in approximately 10.3% of patients with non-syndromic TOF. The deletion tends to have a higher prevalence in patients with TOF-PA. 22q11.2 deletion should be screened in non-syndromic TOF children and genetic counselling may be provided.

  2. Evaluation of Potential Modifiers of the Cardiac Phenotype in the 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Goldmuntz, Elizabeth; Driscoll, Deborah A.; Emanuel, Beverly S.; McDonald-McGinn, Donna; Mei, Minghua; Zackai, Elaine; Mitchell, Laura E.

    2010-01-01

    BACKGROUND The phenotype associated with deletion of the 22q11.2 chromosomal region is highly variable, yet little is known about the source of this variability. Cardiovascular anomalies, including tetralogy of Fallot, truncus arteriosus, interrupted aortic arch type B, perimembranous ventricular septal defects, and aortic arch anomalies, occur in approximately 75% of individuals with a 22q11.2 deletion. METHODS Data from 343 subjects enrolled in a study of the 22q11.2 deletion syndrome were used to evaluate potential modifiers of the cardiac phenotype in this disorder. Subjects with and without cardiac malformations, and subjects with and without aortic arch anomalies were compared with respect to sex and race. In addition, in the subset of subjects from whom a DNA sample was available, genotypes for variants of four genes that are involved in the folate-homocysteine metabolic pathway and that have been implicated as risk factors for other birth defects were compared. Five variants in four genes were genotyped by heteroduplex or restriction digest assays. The chi-square or Fisher’s exact test was used to evaluate the association between the cardiac phenotype and each potential modifier. RESULTS The cardiac phenotype observed in individuals with a 22q11.2 deletion was not significantly associated with either sex or race. The genetic variants that were evaluated also did not appear to be associated with the cardiovascular phenotype. CONCLUSIONS Variation in the cardiac phenotype observed between individuals with a 22q11.2 deletion does not appear to be related to sex, race, or five sequence variants in four folate-related genes that are located outside of the 22q11.2 region. PMID:18770859

  3. Clinical validation of three short forms of the Dutch Wechsler Memory Scale-Fourth Edition (WMS-IV-NL) in a mixed clinical sample.

    Science.gov (United States)

    Bouman, Zita; Hendriks, Marc P H; Van Der Veld, William M; Aldenkamp, Albert P; Kessels, Roy P C

    2016-06-01

    The reliability and validity of three short forms of the Dutch version of the Wechsler Memory Scale-Fourth Edition (WMS-IV-NL) were evaluated in a mixed clinical sample of 235 patients. The short forms were based on the WMS-IV Flexible Approach, that is, a 3-subtest combination (Older Adult Battery for Adults) and two 2-subtest combinations (Logical Memory and Visual Reproduction and Logical Memory and Designs), which can be used to estimate the Immediate, Delayed, Auditory and Visual Memory Indices. All short forms showed good reliability coefficients. As expected, for adults (16-69 years old) the 3-subtest short form was consistently more accurate (predictive accuracy ranged from 73% to 100%) than both 2-subtest short forms (range = 61%-80%). Furthermore, for older adults (65-90 years old), the predictive accuracy of the 2-subtest short form ranged from 75% to 100%. These results suggest that caution is warranted when using the WMS-IV-NL Flexible Approach short forms to estimate all four indices. © The Author(s) 2015.

  4. Psychiatric Disorders From Childhood to Adulthood in 22q11.2 Deletion Syndrome: Results From the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Schneider, Maude; Debbané, Martin; Bassett, Anne S.; Chow, Eva W.C.; Fung, Wai Lun Alan; van den Bree, Marianne B.M.; Owen, Michael; Murphy, Kieran C.; Niarchou, Maria; Kates, Wendy R.; Antshel, Kevin M.; Fremont, Wanda; McDonald-McGinn, Donna M.; Gur, Raquel E.; Zackai, Elaine H.; Vorstman, Jacob; Duijff, Sasja N.; Klaassen, Petra W.J.; Swillen, Ann; Gothelf, Doron; Green, Tamar; Weizman, Abraham; Van Amelsvoort, Therese; Evers, Laurens; Boot, Erik; Shashi, Vandana; Hooper, Stephen R.; Bearden, Carrie E.; Jalbrzikowski, Maria; Armando, Marco; Vicari, Stefano; Murphy, Declan G.; Ousley, Opal; Campbell, Linda E.; Simon, Tony J.; Eliez, Stephan

    2014-01-01

    Objective Chromosome 22q11.2 deletion syndrome is a neurogenetic disorder associated with high rates of schizophrenia and other psychiatric conditions. The authors report what is to their knowledge the first large-scale collaborative study of rates and sex distributions of psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome. The associations among psychopathology, intellect, and functioning were examined in a subgroup of participants. Method The 1,402 participants with 22q11.2 deletion syndrome, ages 6–68 years, were assessed for psychiatric disorders with validated diagnostic instruments. Data on intelligence and adaptive functioning were available for 183 participants ages 6 to 24 years. Results Attention deficit hyperactivity disorder (ADHD) was the most frequent disorder in children (37.10%) and was overrepresented in males. Anxiety disorders were more prevalent than mood disorders at all ages, but especially in children and adolescents. Anxiety and unipolar mood disorders were overrepresented in females. Psychotic disorders were present in 41% of adults over age 25. Males did not predominate in psychotic or autism spectrum disorders. Hierarchical regressions in the subgroup revealed that daily living skills were predicted by the presence of anxiety disorders. Psychopathology was not associated with communication or socialization skills. Conclusions To the authors' knowledge, this is the largest study of psychiatric morbidity in 22q11.2 deletion syndrome. It validates previous findings that this condition is one of the strongest risk factors for psychosis. Anxiety and developmental disorders were also prevalent. These results highlight the need to monitor and reduce the long-term burden of psychopathology in 22q11.2 deletion syndrome. PMID:24577245

  5. Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2

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    Matsuoka, Rumiko; Takao, Atsuyoshi; Kimura, Misa; Kondo, Chisato; Ando, Masahiko; Momma, Kazuo; Imamura, Shin-ichiro [Heart Institute, Tokyo (Japan); Joh-o, Kunitaka [Welfare Pension Hospital, Kyushu (Japan); Ikeda, Kazuo [Sapporo Medical Univ. (Japan); Nishibatake, Makoto [Kagoshima Seikyo Hospital (Japan)

    1994-11-15

    The so-called {open_quotes}conotruncal anomaly face syndrome{close_quotes} (CTAFS) is characterized by a peculiar facial appearance associated with congenital heart disease (CHD), especially cardiac outflow tract defects such as tetralogy of Fallot (TOF), double outlet ring ventricle (DORV), and truncus arteriosus (TAC). CTAFS and the DiGeorge anomaly (DGA) have many similar phenotypic characteristics, suggesting that they share a common cause. In many cases DGA is known to be associated with monosomy for a region of chromosome 22q11.2. Fifty CTAFS patients and 10 DGA patients, 11 parents couples and 10 mothers of CTAFS patients, and 3 parents couples and 2 mothers of DGA patients were examined by fluorescent in situ hybridization (FISH) using the N25 (D22S75) DGCR probe (Oncor). Monosomy for a region of 22q11.2 was found in 42 CTAFS, 9 DGA, 4 mothers, and 1 father who had CTAF without CHD. The remaining 8 CTAFS patients, 1 DGA patient and 1 mother who had questionable CTAF without CHD, showed no such chromosome abnormality. For the control, 60 patients who had CHD without CTAF or other know malformation syndromes were examined and had no deletion of 22q11.2. Therefore, we conclude that CTAFS is a part of the CATCH 22 syndrome; cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia (CATCH) resulting from 22q11.2 deletions. 20 refs., 3 figs., 2 tabs.

  6. Eye Gaze During Face Processing in Children and Adolescents with 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Glaser, Bronwyn; Debbane, Martin; Ottet, Marie-Christine; Vuilleumier, Patrik; Zesiger, Pascal; Antonarakis, Stylianos E.; Eliez, Stephan

    2010-01-01

    Objective: The 22q11.2 deletion syndrome (22q11DS) is a neurogenetic syndrome with high risk for the development of psychiatric disorder. There is interest in identifying reliable markers for measuring and monitoring socio-emotional impairments in 22q11DS during development. The current study investigated eye gaze as a potential marker during a…

  7. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    DEFF Research Database (Denmark)

    Isles, Anthony R; Ingason, Andrés; Lowther, Chelsea

    2016-01-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may...

  8. Delineation of a new chromosome 20q11.2 duplication syndrome including the ASXL1 gene

    DEFF Research Database (Denmark)

    Avila, Magali; Kirchhoff, Eva Maria; Marle, Nathalie

    2013-01-01

    We report on three males with de novo overlapping 7.5, 9.8, and 10 Mb duplication of chromosome 20q11.2. Together with another patient previously published in the literature with overlapping 20q11 microduplication, we show that such patients display common clinical features including metopic ridg...

  9. More Clinical Overlap between 22q11.2 Deletion Syndrome and CHARGE Syndrome than Often Anticipated

    NARCIS (Netherlands)

    Corsten-Janssen, N; Saitta, S C; Hoefsloot, L H; McDonald-McGinn, D M; Driscoll, D A; Derks, R; Dickinson, K A; Kerstjens-Frederikse, W S; Emanuel, B S; Zackai, E H; van Ravenswaaij-Arts, C M A

    CHARGE (coloboma, heart defects, atresia of choanae, retardation of growth and development, genital hypoplasia, and ear abnormalities) and 22q11.2 deletion syndromes are variable, congenital malformation syndromes that show considerable phenotypic overlap. We further explored this clinical overlap

  10. Associations between neurodevelopmental genes, neuroanatomy, and ultra high risk symptoms of psychosis in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Thompson, Carlie A; Karelis, Jason; Middleton, Frank A; Gentile, Karen; Coman, Ioana L; Radoeva, Petya D; Mehta, Rashi; Fremont, Wanda P; Antshel, Kevin M; Faraone, Stephen V; Kates, Wendy R

    2017-04-01

    22q11.2 deletion syndrome is a neurogenetic disorder resulting in the deletion of over 40 genes. Up to 40% of individuals with 22q11.2DS develop schizophrenia, though little is known about the underlying mechanisms. We hypothesized that allelic variation in functional polymorphisms in seven genes unique to the deleted region would affect lobar brain volumes, which would predict risk for psychosis in youth with 22q11.2DS. Participants included 56 individuals (30 males) with 22q11.2DS. Anatomic MR images were collected and processed using Freesurfer. Participants were genotyped for 10 SNPs in the COMT, DGCR8, GNB1L, PIK4CA, PRODH, RTN4R, and ZDHHC8 genes. All subjects were assessed for ultra high risk symptoms of psychosis. Allelic variation of the rs701428 SNP of RTN4R was significantly associated with volumetric differences in gray matter of the lingual gyrus and cuneus of the occipital lobe. Moreover, occipital gray matter volumes were robustly associated with ultra high risk symptoms of psychosis in the presence of the G allele of rs701428. Our results suggest that RTN4R, a relatively under-studied gene at the 22q11 locus, constitutes a susceptibility gene for psychosis in individuals with this syndrome through its alteration of the architecture of the brain. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Confined placental mosaicism for 22q11.2 deletion as the etiology for discordant positive NIPT results.

    Science.gov (United States)

    Bunnell, M; Zhang, C; Lee, C; Bianchi, D W; Wilkins-Haug, L

    2017-04-01

    22q11.2 deletion, the most common microdeletion syndrome within the general population, is estimated to have a prevalence of 1 in 3000 to 6000. Non-invasive prenatal testing has recently expanded to include screening for several microdeletions including 22q11.2. Given the expansion of prenatal screening options to include microdeletions, it is important to understand the limits of this technology and the variety of reasons that a discordant positive result can occur. Here, we describe a case of a pregnant woman who received a positive non-invasive prenatal maternal plasma screen for 22q11.2 deletion. Maternal and postnatal neonatal peripheral blood cytogenetic, PCR, and fluorescence in situ hybridization studies were normal, but the placenta was mosaic for 22q11.2 deletion in two of three biopsy sites. This case illustrates both the complexities of pre- and post-test counseling for microdeletion screening and the potential for a discordant positive microdeletion result because of confined placental mosaicism. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

  12. The 22Q11.2 Deletion in Children: High Rate of Autistic Disorders and Early Onset of Psychotic Symptoms

    Science.gov (United States)

    Vorstman, Jacob A. S.; Morcus, Monique E. J.; Duijff, Sasja N.; Klaassen, Petra W. J.; Heineman-de, Josien A.; Beemer, Frits A.; Swaab, Hanna; Kahn, Rene S.; van Engeland, Herman

    2006-01-01

    Objective: To examine psychopathology and influence of intelligence level on psychiatric symptoms in children with the 22q11.2 deletion syndrome (22q11DS). Method: Sixty patients, ages 9 through 18 years, were evaluated. Assessments followed standard protocols, including structured and semistructured interviews of parents, videotaped psychiatric…

  13. The Neural Correlates of Non-Spatial Working Memory in Velocardiofacial Syndrome (22q11.2 Deletion Syndrome)

    Science.gov (United States)

    Kates, Wendy R.; Krauss, Beth R.; AbdulSabur, Nuria; Colgan, Deirdre; Antshel, Kevin M.; Higgins, Anne Marie; Shprintzen, Robert J.

    2007-01-01

    Velocardiofacial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a neurogenetic disorder that is associated with both learning disabilities and a consistent neuropsychological phenotype, including deficits in executive function, visuospatial perception, and working memory. Anatomic imaging studies have identified significant…

  14. Autism Spectrum Disorders and Symptoms in Children with Molecularly Confirmed 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Fine, Sarah E.; Weissman, Alison; Gerdes, Marsha; Pinto-Martin, Jennifer; Zackai, Elaine H.; McDonald-McGinn, Donna M.; Emanuel, Beverly S.

    2005-01-01

    In this study, we assessed the presence of autism spectrum disorders (ASD) among children with a confirmed 22q11.2 deletion (n = 98). The children's caregivers completed screening measures of ASD behaviors, and for those whose scores indicated significant levels of these behaviors, a standardized diagnostic interview (Autism Diagnostic…

  15. Childhood Predictors of Written Expression in Late Adolescents with 22q11.2 Deletion Syndrome: A Longitudinal Study

    Science.gov (United States)

    Hamsho, N.; Antshel, K. M.; Eckert, T. L.; Kates, W. R.

    2017-01-01

    Background: 22q11.2 deletion syndrome (22q11DS) is the second most prevalent genetic syndrome and has a characteristic academic and behavioural phenotype. The primary objective of the current study was to examine the childhood predictors of written expression achievement in adolescents with 22q11DS. Written expression is an important skill that…

  16. A Longitudinal Examination of the Psychoeducational, Neurocognitive, and Psychiatric Functioning in Children with 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Hooper, Stephen R.; Curtiss, Kathleen; Schoch, Kelly; Keshavan, Matcheri S.; Allen, Andrew; Shashi, Vandana

    2013-01-01

    The present study sought to examine the longitudinal psychoeducational, neurocognitive, and psychiatric outcomes of children and adolescents with chromosome 22q11.2 deletion syndrome (22q11DS), a population with a high incidence of major psychiatric illnesses appearing in late adolescence/early adulthood. Little is known of the developmental…

  17. [Absent or hypoplastic thymus: A marker for 22q11.2 microdeletion syndrome in case of polyhydramnios].

    Science.gov (United States)

    Lamouroux, A; Mousty, E; Prodhomme, O; Bigi, N; Le Gac, M-P; Letouzey, V; De Tayrac, R; Mares, P

    2016-04-01

    In prenatal diagnosis of 22q11.2 microdeletion syndrome, without cardiac malformation or multiple associated congenital anomalies, we study the presence of polyhydramnios and its association with thymic dysgenesis. This was a multicenter retrospective observational study. It was performed in two multidisciplinary centers for prenatal diagnosis in the south of France between January 1, 2010 and June 30, 2013. Inclusion criteria were prenatal diagnosis of 22q11.2 deletion syndrome. We excluded from the study any fetus with cardiac malformation or multiple associated congenital anomalies. During the inclusion period, eleven antenatal diagnoses of 22q11.2 microdeletion syndrome have been made. Six cases were excluded: 5 fetuses with cardiac malformation and one with multiple associated congenital anomalies. Therefore, five cases of isolated polyhydramnios were included. All 5 fetuses had a thymic dysgenesis: 3 had a thymic agenesis and 1 thymic hypoplasia diagnosed by sonography and 1 had a thymic agenesis diagnosed by retrospective reading of fetal MRI. When faced with a polyhydramnios, the presence of a thymic dysgenesis should be search for by ultrasound screening and would alert to the possibility of a 22q11.2 microdeletion syndrome. The confirmation of this is diagnosis by amniocentesis would enable improved antenatal support for parents and would enable early implementation of the multidisciplinary neonatal care that is required to avoid serious complications of this syndrome. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Memory in Intellectually Matched Groups of Young Participants with 22q11.2 Deletion Syndrome and Those with Schizophrenia

    Science.gov (United States)

    Kravariti, Eugenia; Jacobson, Clare; Morris, Robin; Frangou, Sophia; Murray, Robin M.; Tsakanikos, Elias; Habel, Alex; Shearer, Jo

    2010-01-01

    The 22q11.2 deletion syndrome (22qDS) and schizophrenia have genetic and neuropsychological similarities, but are likely to differ in memory profile. Confirming differences in memory function between the two disorders, and identifying their genetic determinants, can help to define genetic subtypes in both syndromes, identify genetic risk factors…

  19. Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Merico, Daniele; Zarrei, Mehdi; Costain, Gregory; Ogura, Lucas; Alipanahi, Babak; Gazzellone, Matthew J.; Butcher, Nancy J.; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Chow, Eva W. C.; Andrade, Danielle M.; Frey, Brendan J.; Marshall, Christian R.; Scherer, Stephen W.; Bassett, Anne S.

    2015-01-01

    Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of DGCR8 haploinsufficiency. In a proof-of-principle study to assess the power of this model, we used high-quality, whole-genome sequencing of nine individuals with 22q11.2 deletions and extreme phenotypes (schizophrenia, or no psychotic disorder at age >50 years). The schizophrenia group had a greater burden of rare, damaging variants impacting protein-coding neurofunctional genes, including genes involved in neuron projection (nominal P = 0.02, joint burden of three variant types). Variants in the intact 22q11.2 region were not major contributors. Restricting to genes affected by a DGCR8 mechanism tended to amplify between-group differences. Damaging variants in highly conserved long intergenic noncoding RNA genes also were enriched in the schizophrenia group (nominal P = 0.04). The findings support the 22q11.2 deletion model as a threshold-lowering first hit for schizophrenia risk. If applied to a larger and thus better-powered cohort, this appears to be a promising approach to identify genome-wide rare variants in coding and noncoding sequence that perturb gene networks relevant to idiopathic schizophrenia. Similarly designed studies exploiting genetic models may prove useful to help delineate the genetic architecture of other complex phenotypes. PMID:26384369

  20. Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Vorstman, Jacob A S|info:eu-repo/dai/nl/304817023; Breetvelt, Elemi J.|info:eu-repo/dai/nl/357937414; Duijff, Sasja N.|info:eu-repo/dai/nl/30481914X; Eliez, Stephan; Schneider, Maude; Jalbrzikowski, Maria; Armando, Marco; Vicari, Stefano; Shashi, Vandana; Hooper, Stephen R.; Chow, Eva W C; Fung, Wai Lun Alan; Butcher, Nancy J.; Young, Donald A.; McDonald-McGinn, Donna M.; Vogels, Annick; Van Amelsvoort, Therese; Gothelf, Doron; Weinberger, Ronnie; Weizman, Abraham; Klaassen, Petra W J; Koops, Sanne; Kates, Wendy R.; Antshel, Kevin M.; Simon, Tony J.; Ousley, Opal Y.; Swillen, Ann; Gur, Raquel E.; Bearden, Carrie E.; Kahn, René S.|info:eu-repo/dai/nl/073778532; Bassett, Anne S.; Emanuel, Beverly S.; Zackai, Elaine H.; Kushan, Leila; Fremont, Wanda; Schoch, Kelly; Stoddard, Joel; Cubells, Joseph; Fu, Fiona; Campbell, Linda E.; Fritsch, Rosemarie; Vergaelen, Elfi; Neeleman, Marjolein; Boot, Erik; Debbané, Martin; Philip, Nicole; Green, Tamar; Van DenBree, Marianne B M; Murphy, Declan; Canyelles, Jaume Morey; Arango, Celso; Murphy, Kieran C.; Pontillo, Maria

    2015-01-01

    Importance: Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age.Objective: To determine whether

  1. Overlapping Numerical Cognition Impairments in Children with Chromosome 22q11.2 Deletion or Turner Syndromes

    Science.gov (United States)

    Simon, T. J.; Takarae, Y.; DeBoer, T.; McDonald-McGinn, D. M.; Zackai, E. H.; Ross, J. L.

    2008-01-01

    Children with one of two genetic disorders (chromosome 22q11.2 deletion syndrome and Turner syndrome) as well typically developing controls, participated in three cognitive processing experiments. Two experiments were designed to test cognitive processes involved in basic aspects numerical cognition. The third was a test of simple manual motor…

  2. Ultrasonographic Findings of Renal Cell Carcinomas Associated with Xp11.2 Translocation/TFE3 Gene Fusion

    Directory of Open Access Journals (Sweden)

    Wenwu Ling

    2017-01-01

    Full Text Available Objective. This study was to investigate the features of renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions (Xp11.2-RCC on conventional ultrasound (US and contrast-enhanced ultrasound (CEUS. Methods. US and CEUS features of twenty-two cases with histopathologically proven Xp11.2-RCC were retrospectively reviewed. Results. 22 patients (11 males, 11 females were included in this study, with a mean age of 28.3 ± 20.4 years. Eight tumors (36.3%, 8/22 were in left kidney, and 14 tumors (63.7%, 14/22 were in right kidney. All tumors (100%, 22/22 were mixed echogenicity type. 13 tumors (59.1%, 13/22 presented small dotted calcifications. The boundary of 14 tumors (63.6%, 14/22 was sharp and the other 8 tumors’ (36.4%, 8/22 boundary was blurry. By CEUS, in early phase, the solid element of all tumors showed obvious enhancement. In delayed phase, 13 tumors showed hypoenhancement, seven tumors showed isoenhancement, and 2 tumors showed hyperenhancement. There were irregular nonenhancement areas in all tumors inside. Conclusions. By US and CEUS, when children and adolescents were found to have hyperechoic mixed tumor in kidney with sharp margin and calcification, and the tumors showed obvious enhancement and hypoenhancement with irregular nonenhancement areas in the tumor in early phase and delayed phase, respectively, Xp11.2-RCC should be suspected.

  3. Facial emotion perception by intensity in children and adolescents with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Leleu, Arnaud; Saucourt, Guillaume; Rigard, Caroline; Chesnoy, Gabrielle; Baudouin, Jean-Yves; Rossi, Massimiliano; Edery, Patrick; Franck, Nicolas; Demily, Caroline

    2016-03-01

    Difficulties in the recognition of emotions in expressive faces have been reported in people with 22q11.2 deletion syndrome (22q11.2DS). However, while low-intensity expressive faces are frequent in everyday life, nothing is known about their ability to perceive facial emotions depending on the intensity of expression. Through a visual matching task, children and adolescents with 22q11.2DS as well as gender- and age-matched healthy participants were asked to categorise the emotion of a target face among six possible expressions. Static pictures of morphs between neutrality and expressions were used to parametrically manipulate the intensity of the target face. In comparison to healthy controls, results showed higher perception thresholds (i.e. a more intense expression is needed to perceive the emotion) and lower accuracy for the most expressive faces indicating reduced categorisation abilities in the 22q11.2DS group. The number of intrusions (i.e. each time an emotion is perceived as another one) and a more gradual perception performance indicated smooth boundaries between emotional categories. Correlational analyses with neuropsychological and clinical measures suggested that reduced visual skills may be associated with impaired categorisation of facial emotions. Overall, the present study indicates greater difficulties for children and adolescents with 22q11.2DS to perceive an emotion in low-intensity expressive faces. This disability is subtended by emotional categories that are not sharply organised. It also suggests that these difficulties may be associated with impaired visual cognition, a hallmark of the cognitive deficits observed in the syndrome. These data yield promising tracks for future experimental and clinical investigations.

  4. The Number of Genomic Copies at the 16p11.2 Locus Modulates Language, Verbal Memory, and Inhibition.

    Science.gov (United States)

    Hippolyte, Loyse; Maillard, Anne M; Rodriguez-Herreros, Borja; Pain, Aurélie; Martin-Brevet, Sandra; Ferrari, Carina; Conus, Philippe; Macé, Aurélien; Hadjikhani, Nouchine; Metspalu, Andres; Reigo, Anu; Kolk, Anneli; Männik, Katrin; Barker, Mandy; Isidor, Bertrand; Le Caignec, Cédric; Mignot, Cyril; Schneider, Laurence; Mottron, Laurent; Keren, Boris; David, Albert; Doco-Fenzy, Martine; Gérard, Marion; Bernier, Raphael; Goin-Kochel, Robin P; Hanson, Ellen; Green Snyder, LeeAnne; Ramus, Franck; Beckmann, Jacques S; Draganski, Bogdan; Reymond, Alexandre; Jacquemont, Sébastien

    2016-07-15

    Deletions and duplications of the 16p11.2 BP4-BP5 locus are prevalent copy number variations (CNVs), highly associated with autism spectrum disorder and schizophrenia. Beyond language and global cognition, neuropsychological assessments of these two CNVs have not yet been reported. This study investigates the relationship between the number of genomic copies at the 16p11.2 locus and cognitive domains assessed in 62 deletion carriers, 44 duplication carriers, and 71 intrafamilial control subjects. IQ is decreased in deletion and duplication carriers, but we demonstrate contrasting cognitive profiles in these reciprocal CNVs. Deletion carriers present with severe impairments of phonology and of inhibition skills beyond what is expected for their IQ level. In contrast, for verbal memory and phonology, the data may suggest that duplication carriers outperform intrafamilial control subjects with the same IQ level. This finding is reminiscent of special isolated skills as well as contrasting language performance observed in autism spectrum disorder. Some domains, such as visuospatial and working memory, are unaffected by the 16p11.2 locus beyond the effect of decreased IQ. Neuroimaging analyses reveal that measures of inhibition covary with neuroanatomic structures previously identified as sensitive to 16p11.2 CNVs. The simultaneous study of reciprocal CNVs suggests that the 16p11.2 genomic locus modulates specific cognitive skills according to the number of genomic copies. Further research is warranted to replicate these findings and elucidate the molecular mechanisms modulating these cognitive performances. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Risk of 22q11.2 deletion in fetuses with right aortic arch and without intracardiac anomalies.

    Science.gov (United States)

    Perolo, A; De Robertis, V; Cataneo, I; Volpe, N; Campobasso, G; Frusca, T; Ghi, T; Prandstraller, D; Pilu, G; Volpe, P

    2016-08-01

    To assess the risk of 22q11.2 deletion in fetuses with a prenatal diagnosis of right aortic arch without intracardiac anomalies (RAA-no ICA). This was a retrospective study of all fetuses with RAA-no ICA diagnosed prenatally at three referral centers, between 2004 and 2014. A detailed sonographic examination was performed in each case, including visualization of the thymus and of the head and neck vessels to identify the presence of an aberrant left subclavian artery (ALSA). Karyotyping and fluorescence in situ hybridization analysis for diagnosis of 22q11.2 deletion were always offered either prenatally or postnatally. Clinical and echocardiographic examinations were performed in livebirths and a postmortem examination in cases of termination of pregnancy. During the study period, 85 fetuses were diagnosed prenatally with RAA-no ICA. Genetic or clinical data were not available for three cases and these were excluded from analysis. 22q11.2 deletion was found in 7/82 cases (8.5% (95% CI, 3.8-17.3%)). The thymus was small or non-visualized in all seven cases and additional abnormal sonographic findings were present in four. 22q11.2 deletion is present in a clinically significant proportion of fetuses with a prenatal diagnosis of RAA-no ICA. In such cases, a detailed sonographic examination, with assessment of the thymus in particular, may be useful to further define the level of risk for 22q11.2 deletion. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  6. Non-pharmacological treatment of psychiatric disorders in individuals with 22q11.2 deletion syndrome; a systematic review.

    Science.gov (United States)

    Buijs, Petra C M; Bassett, Anne S; Boot, Erik

    2018-01-24

    22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of anxiety disorders, psychotic disorders, and other psychiatric conditions. In the general population, psychiatric disorders are treated with proven pharmacological and non-pharmacological therapies, such as cognitive behavioral therapy (CBT). To begin to assess the feasibility and efficacy of non-pharmacological therapies in 22q11.2DS, we performed a systematic search to identify literature on non-pharmacological interventions for psychiatric disorders in individuals with 22q11.2DS. Of 1,240 individual publications up to mid-2016 initially identified, 11 met inclusion criteria. There were five literature reviews, five publications reporting original research (two originating from a single study), and one publication not fitting either category that suggested adaptations to an intervention without providing scientific evidence. None of the original research involved direct study of the evidence-based non-pharmacological therapies available for psychiatric disorders. Rather, these four studies involved computer-based or group interventions aimed at improving neuropsychological deficits that may be associated with psychiatric disorders. Although the sample sizes were relatively small (maximum 28 participants in the intervention group), these reports documented the promising feasibility of these interventions, and improvements in domains of neuropsychological functioning, including working memory, attention, and social cognition. The results of this review underline the need for research into the feasibility and efficacy of non-pharmacological treatments of psychiatric disorders in individuals with 22q11.2DS to inform clinical care, using larger samples, and optimally, standard randomized, placebo-controlled, clinical trials methodology. © 2018 Wiley Periodicals, Inc.

  7. Distal deletion at 22q11.2 as differential diagnosis in Craniofacial Microsomia: Case report and literature review.

    Science.gov (United States)

    Spineli-Silva, Samira; Bispo, Luciana M; Gil-da-Silva-Lopes, Vera L; Vieira, Társis P

    2017-12-27

    Craniofacial Microsomia (CFM) also known as Oculo-auriculo-vertebral Spectrum (OAVS) or Goldenhar Syndrome, presents wide phenotypic and etiological heterogeneity. It affects mainly the structures originated from the first and second pharyngeal arches. In addition, other major anomalies may also be found, including congenital heart diseases. In this study, we report a patient with distal deletion in the 22q11.2 region and a phenotype which resembles CFM. The proband is a girl, who presented bilateral preauricular tags, left auditory canal stenosis, malar hypoplasia, cleft lip and palate, mild asymmetry of soft tissue in face, congenital heart disease, intestinal atresia, annular pancreas and hydronephrosis. The genomic imbalances investigation by Multiplex Ligation-dependent Probe Amplification (MLPA) and Chromosomal Microarray Analysis (CMA) revealed a distal deletion of 1,048 kb at 22q11.2 encompassing the region from Low Copy Repeats (LCRs) D to E. We did review of the literature and genotype-phenotype correlation. This is the sixth case of distal 22q11.2 deletion resembling CFM and the second encompassing the region between LCRs D to E. All cases share some phenotypic signs, such as preauricular tags, facial asymmetry, cleft lip and palate, and congenital heart diseases. Candidate genes in this region have been studied by having an important role in pharyngeal arches developmental and in congenital heart diseases, such as HIC2, YPEL1and MAPK1/ERK2. This case corroborates the phenotypic similarity between 22q11.2 distal deletion and CFM/OAVS. It also contributes to genotype-phenotype correlation and reinforces that candidate genes for CFM, in the 22q11.2 region, might be located between LCRs D and E. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Characterization of the past and current duplication activities in the human 22q11.2 region

    Science.gov (United States)

    2011-01-01

    Background Segmental duplications (SDs) on 22q11.2 (LCR22), serve as substrates for meiotic non-allelic homologous recombination (NAHR) events resulting in several clinically significant genomic disorders. Results To understand the duplication activity leading to the complicated SD structure of this region, we have applied the A-Bruijn graph algorithm to decompose the 22q11.2 SDs to 523 fundamental duplication sequences, termed subunits. Cross-species syntenic analysis of primate genomes demonstrates that many of these LCR22 subunits emerged very recently, especially those implicated in human genomic disorders. Some subunits have expanded more actively than others, and young Alu SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events. Many copy number variations (CNVs) exist on 22q11.2, some flanked by SDs. Interestingly, two chromosome breakpoints for 13 CNVs (mean length 65 kb) are located in paralogous subunits, providing direct evidence that SD subunits could contribute to CNV formation. Sequence analysis of PACs or BACs identified extra CNVs, specifically, 10 insertions and 18 deletions within 22q11.2; four were more than 10 kb in size and most contained young AluYs at their breakpoints. Conclusions Our study indicates that AluYs are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and Alu elements. PMID:21269513

  9. Characterization of the past and current duplication activities in the human 22q11.2 region

    Directory of Open Access Journals (Sweden)

    Morrow Bernice

    2011-01-01

    Full Text Available Abstract Background Segmental duplications (SDs on 22q11.2 (LCR22, serve as substrates for meiotic non-allelic homologous recombination (NAHR events resulting in several clinically significant genomic disorders. Results To understand the duplication activity leading to the complicated SD structure of this region, we have applied the A-Bruijn graph algorithm to decompose the 22q11.2 SDs to 523 fundamental duplication sequences, termed subunits. Cross-species syntenic analysis of primate genomes demonstrates that many of these LCR22 subunits emerged very recently, especially those implicated in human genomic disorders. Some subunits have expanded more actively than others, and young Alu SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events. Many copy number variations (CNVs exist on 22q11.2, some flanked by SDs. Interestingly, two chromosome breakpoints for 13 CNVs (mean length 65 kb are located in paralogous subunits, providing direct evidence that SD subunits could contribute to CNV formation. Sequence analysis of PACs or BACs identified extra CNVs, specifically, 10 insertions and 18 deletions within 22q11.2; four were more than 10 kb in size and most contained young AluYs at their breakpoints. Conclusions Our study indicates that AluYs are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and Alu elements.

  10. Individuals with 22q11.2 Deletion Syndrome Are Impaired at Explicit, but Not Implicit, Discrimination of Local Forms Embedded in Global Structures

    Science.gov (United States)

    Giersch, Anne; Glaser, Bronwyn; Pasca, Catherine; Chabloz, Mélanie; Debbané, Martin; Eliez, Stephan

    2014-01-01

    Individuals with 22q11.2 deletion syndrome (22q11.2DS) are impaired at exploring visual information in space; however, not much is known about visual form discrimination in the syndrome. Thirty-five individuals with 22q11.2DS and 41 controls completed a form discrimination task with global forms made up of local elements. Affected individuals…

  11. Mother-Child Interaction as a Window to a Unique Social Phenotype in 22q11.2 Deletion Syndrome and in Williams Syndrome

    Science.gov (United States)

    Weisman, Omri; Feldman, Ruth; Burg-Malki, Merav; Keren, Miri; Geva, Ronny; Diesendruck, Gil; Gothelf, Doron

    2015-01-01

    Mother-child interactions in 22q11.2 Deletion syndrome (22q11.2DS) and Williams syndrome (WS) were coded for maternal sensitivity/intrusiveness, child's expression of affect, levels of engagement, and dyadic reciprocity. WS children were found to express more positive emotions towards their mothers compared to 22q11.2DS children and those with…

  12. Síndrome de deleção 22q11.2: compreendendo o CATCH22 22q11.2 deletion syndrome: catching the CATCH22

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano M. Rosa

    2009-06-01

    Full Text Available OBJETIVO:Realizar uma revisão dos aspectos históricos, epidemiológicos, clínicos, etiológicos e laboratoriais da síndrome de deleção 22q11.2, salientando-se a importância e as dificuldades do seu diagnóstico. FONTES DE DADOS: Pesquisa nas bases de dados Medline, Lilacs e SciELO, além da Internet e capítulos de livros em inglês, acerca de publicações feitas entre 1980 e 2008. Para isso, utilizaram-se os descritores "22q11", "DiGeorge", "Velocardiofacial" e "CATCH22". SÍNTESE DOS DADOS: A síndrome de deleção 22q11.2, também conhecida como síndrome de DiGeorge ou velocardiofacial, foi identificada no começo da década de 1990. A microdeleção 22q11.2 é considerada uma das síndromes de microdeleção genética mais frequentes em seres humanos. Caracteriza-se por um espectro fenotípico bastante amplo, com mais de 180 achados clínicos já descritos do ponto de vista físico e comportamental. Contudo, nenhum achado é patognomônico ou mesmo obrigatório. A maioria dos pacientes apresenta uma deleção pequena, detectada somente por técnicas de genética molecular, como a hibridização in situ fluorescente. Apresenta padrão de herança autossômico dominante, ou seja, indivíduos acometidos apresentam um risco de 50% de transmiti-la a seus filhos. CONCLUSÕES: Pacientes com a síndrome de deleção 22q11.2 frequentemente necessitam, ao longo de suas vidas, de um grande número de intervenções médicas e hospitalizações. O diagnóstico precoce é fundamental para a adequada avaliação e manejo clínico dos indivíduos e seus familiares.OBJECTIVE:To review historical, epidemiological, clinical, etiological and laboratorial aspects of the 22q11.2 deletion syndrome, highlighting the importance of the diagnosis and its difficulties. DATA SOURCES: MedLine, Lilacs e SciELO databases, as well as internet and book chapters written in English, were searched for the period of 1980-2008, with the following descriptors "22q11

  13. [22q11.2 microdeletion syndrome: Analysis of the care pathway before the genetic diagnosis].

    Science.gov (United States)

    Ingrao, T; Lambert, L; Valduga, M; Bosser, G; Albuisson, E; Leheup, B

    2017-11-01

    22q11.2 deletion syndrome (22q11.2DS) is a very broad phenotypic spectrum disorder. It can affect many organs or systems. 22q11.2DS is the most common microdeletion syndrome in humans, with a prevalence ranging from one in every 2000 to one in 4000 newborns. It seems to be more prevalent than reported and under-recognized or undiagnosed because of its inherent clinical variability and heterogeneity. In France, 15,000 patients may be affected by this disease, more than half without knowing it. The aim of this study was to analyze the care pathway before the genetic diagnosis of 22q11.2DS. We conducted a single-center, retrospective analysis of postnatally diagnosed patients recruited by the cytogenetic laboratory of Nancy (France) from January 2000 to December 2015. Clinical data were first collected by consulting the medical files of patients and then by calling them directly. Written informed consent was obtained and the study was approved by local research ethics boards. Data concerned only clinical features before the diagnosis. The cohort consisted of 32 individuals with 22q11.2DS. The average age at diagnosis was 9 years and 2 months and the median age was 2 years and 11 months. Fetal echography was abnormal in 15 pregnancies. During the neonatal period, the most important features were eating difficulties and congenital malformations (n=20), with a majority of complex heart diseases (n=16), dominated by conotruncal malformations (n=6). In case of malformation, the average age at diagnosis decreased to 2 years and 6 months. A congenital heart disease brought the average age of diagnosis down to 2 years and 6 months. Hypocalcemia and dysmorphism were also classical features (n=14). Before the age of 3 years, speech delay occurred in nine patients. After 3 years of age, rhinolalia was predominant (n=11). Academic disabilities were present in all subjects. At least 14 patients had a de novo deletion. Five patients were diagnosed within genetic

  14. 22q11.2 Deletion Syndrome is under-recognised in adult patients with tetralogy of Fallot and pulmonary atresia

    OpenAIRE

    van Engelen, K.; Topf, A.; Keavney, B.D.; Goodship, J.A.; van der Velde, E.T.; Baars, M.J.H.; Snijder, S.; Moorman, A.F.; Postma, A.V.; Mulder, B.J.M.

    2010-01-01

    Background Three quarters of patients with 22q11.2 Deletion Syndrome (22q11.2DS) have congenital heart disease (CHD), typically conotruncal heart defects. Although it is currently common practice to test all children with typical CHD for 22q11.2DS, many adult patients have not been tested in the past and therefore 22q11.2DS might be under-recognised in adults. Objectives To determine the prevalence of 22q11.2DS in adults with tetralogy of Fallot (TOF) and pulmonary atresia (PA)/ventricular se...

  15. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    Science.gov (United States)

    Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George

    2016-01-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

  16. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders.

    Directory of Open Access Journals (Sweden)

    Anthony R Isles

    2016-05-01

    Full Text Available Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS region have been associated with developmental delay (DD, autism spectrum disorder (ASD and schizophrenia (SZ. Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA, but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15 or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of

  17. Aksesuar Mental Foramen: Konik Işınlı Bilgisayarlı Tomografi Bulguları-Accessory Mental Foramen: Findings of cone-beam computed tomography

    OpenAIRE

    Sinanoğlu, Alper; Coşkunses, Fatih; Kan, Bahadır; Altan, Ayşe

    2014-01-01

    Aksesuar mental foramen (AMF), MF bölgesinde, MF’in birden fazla olması durumunda asıl foramenin dışındaki diğer foramenler olarak tanımlanmıştır. AMF’in lokalizasyon ve sayı varyasyonlarının ırk ve etnik yapıya göre farklılık gösterdiği rapor edilmiştir. Bu anatomik varyasyonun değerlendirilmesinde konik ışınlı bilgisayarlı tomografi kullanımı, ilgili alanın 3 boyutlu rekonstrüksiyonlarına ve kesitsel olarak değerlendirilmesine olanak sağlamaktadır. Bu çalışmada 23 yaşındaki kadın hastada te...

  18. Aksesuar mental foramenin konik-ışınlı bilgisayarlı tomografi ile görüntülenmesi: iki olgu bildirimi

    OpenAIRE

    Gümüşok, Mustafa; Zafersoy Akarslan, Zühre; Üçok, Özlem

    2015-01-01

    TANITIM: Mental foramen mandibulanın önemli anatomik yapılarındandır. Bazı bireylerde mental foramen birden fazla sayıda olabilmekte ve böyle vakalarda aksesuar mental foramen olarak adlandırılmaktadır. Aksesuar mental foramenler, mental foramene kıyasla daha küçük boyutlarda olmalarından dolayı genellikle geleneksel yöntemlerle görüntüleme esnasında teşhis edilememektedir. Konik-ışınlı bilgisayarlı tomografi, maksillofasiyal bölgedeki yapıların radyografik görüntülerinin her üç ortogonal düz...

  19. NL MIND-BEST: a web server for ligands and proteins discovery--theoretic-experimental study of proteins of Giardia lamblia and new compounds active against Plasmodium falciparum.

    Science.gov (United States)

    González-Díaz, Humberto; Prado-Prado, Francisco; Sobarzo-Sánchez, Eduardo; Haddad, Mohamed; Maurel Chevalley, Séverine; Valentin, Alexis; Quetin-Leclercq, Joëlle; Dea-Ayuela, María A; Teresa Gomez-Muños, María; Munteanu, Cristian R; José Torres-Labandeira, Juan; García-Mera, Xerardo; Tapia, Ricardo A; Ubeira, Florencio M

    2011-05-07

    There are many protein ligands and/or drugs described with very different affinity to a large number of target proteins or receptors. In this work, we selected Ligands or Drug-target pairs (DTPs/nDTPs) of drugs with high affinity/non-affinity for different targets. Quantitative Structure-Activity Relationships (QSAR) models become a very useful tool in this context to substantially reduce time and resources consuming experiments. Unfortunately most QSAR models predict activity against only one protein target and/or have not been implemented in the form of public web server freely accessible online to the scientific community. To solve this problem, we developed here a multi-target QSAR (mt-QSAR) classifier using the MARCH-INSIDE technique to calculate structural parameters of drug and target plus one Artificial Neuronal Network (ANN) to seek the model. The best ANN model found is a Multi-Layer Perceptron (MLP) with profile MLP 20:20-15-1:1. This MLP classifies correctly 611 out of 678 DTPs (sensitivity=90.12%) and 3083 out of 3408 nDTPs (specificity=90.46%), corresponding to training accuracy=90.41%. The validation of the model was carried out by means of external predicting series. The model classifies correctly 310 out of 338 DTPs (sensitivity=91.72%) and 1527 out of 1674 nDTP (specificity=91.22%) in validation series, corresponding to total accuracy=91.30% for validation series (predictability). This model favorably compares with other ANN models developed in this work and Machine Learning classifiers published before to address the same problem in different aspects. We implemented the present model at web portal Bio-AIMS in the form of an online server called: Non-Linear MARCH-INSIDE Nested Drug-Bank Exploration & Screening Tool (NL MIND-BEST), which is located at URL: http://miaja.tic.udc.es/Bio-AIMS/NL-MIND-BEST.php. This online tool is based on PHP/HTML/Python and MARCH-INSIDE routines. Finally we illustrated two practical uses of this server with two

  20. Deleção 22q11.2 em pacientes com defeito cardíaco conotruncal e fenótipo da síndrome da deleção 22q11.2 Deleción 22q11.2 en pacientes con defecto cardiaco conotruncal y fenotipo del síndrome de la deleción 22q11.2 22q11.2 deletion in patients with conotruncal heart defect and del22q syndrome phenotype

    Directory of Open Access Journals (Sweden)

    Sintia Iole Nogueira Belangero

    2009-04-01

    Full Text Available FUNDAMENTO: A síndrome da deleção 22q11.2 é a mais freqüente síndrome de microdeleção humana. O fenótipo é altamente variável e caracterizado por defeito cardíaco conotruncal, dismorfias faciais, insuficiência velofaríngea, dificuldade de aprendizagem e retardo mental. OBJETIVO: O objetivo deste trabalho foi investigar a freqüência da deleção 22q11.2 em uma amostra brasileira de indivíduos portadores de cardiopatia conontrucal isolada e do fenótipo da síndrome da deleção 22q11.2. MÉTODOS: Vinte e nove pacientes foram estudados por meio de citogenética clássica, por hibridação in situ fluorescente (FISH e por técnicas moleculares. RESULTADOS: A análise citogenética por meio de bandamento G revelou cariótipo normal em todos os pacientes, com exceção de um que apresentou cariótipo 47,XX,+idic(22(q11.2. Com o uso de técnicas moleculares, a deleção foi observada em 25% dos pacientes, todos portadores do fenótipo da síndrome da deleção 22q11.2. Em nenhum dos casos, a deleção foi herdada dos pais. A freqüência da deleção 22q11.2 foi maior no grupo de pacientes portadores do espectro clínico da síndrome da deleção 22q11.2 do que no grupo de pacientes com cardiopatia conotruncal isolada. CONCLUSÃO: A investigação da presença da deleção e sua correlação com os dados clínicos dos pacientes podem auxiliar os pacientes e suas famílias a terem um melhor aconselhamento genético e um seguimento clínico mais adequado.FUNDAMENTO: El síndrome de la deleción 22q11.2 es el más frecuente síndrome de microdeleción humana. El fenotipo, altamente variable, se caracteriza por defecto cardiaco conotruncal, dismorfias faciales, insuficiencia velofaríngea, dificultad de aprendizaje y retardo mental. OBJETIVO: El objetivo de este trabajo fue investigar la frecuencia tanto de la deleción 22q11.2 en una muestra brasileña de individuos portadores de cardiopatía conotrucal aislada, como del fenotipo del s

  1. SPCE based glucose sensor employing novel thermostable glucose dehydrogenase, FADGDH: blood glucose measurement with 150nL sample in one second.

    Science.gov (United States)

    Yamaoka, Hideaki; Sode, Koji

    2007-01-01

    Self-monitoring of blood glucose (SMBG) is an important component of the modern therapy for diabetes mellitus. Thanks to the current progress in electronics and sensor fabrication technology, both the time and the blood sample volume required for the measurement have decreased drastically. However, devices that work with an even smaller sample volume and a shorter measurement time are in demand. A disposable glucose sensor that works with an ultra-small sample volume was developed employing the novel thermostable glucose-dehydrogenase (FADGDH) complex composed of a catalytic subunit, an electron transfer subunit (cytochrome c), and a small subunit. The electrode is a screen-printed carbon electrode (SPCE), and hexaammineruthenium (III) chloride (Ru complex) is utilized as the electron mediator. A disposable enzyme sensor was constructed by depositing the FADGDH complex and Ru complex onto the SPCE, and the sensor performance was evaluated. Whole-blood glucose can be measured within 1 sec using this enzyme sensor and a 150-nL whole-blood sample, with high precision (>0.99br>) and high reproducibility (CV) within the glucose concentration range of 0-533 mg/dL. The sensor reading was stable for more than 60 days even at 70 degrees C. The simplicity of the construction and the high precision of this FADGDH-based glucose biosensor makes it an alternative to previously reported commercially available glucose sensors. Especially the sample volume of 150 nL and the 1-sec measurement time are the highest specifications in the world for currently available glucose sensors designed for the SMBG.

  2. Chromosome 22q11.2 Deletion Syndrome Presenting as Adult Onset Hypoparathyroidism: Clues to Diagnosis from Dysmorphic Facial Features

    Directory of Open Access Journals (Sweden)

    Sira Korpaisarn

    2013-01-01

    Full Text Available We report a 26-year-old Thai man who presented with hypoparathyroidism in adulthood. He had no history of cardiac disease and recurrent infection. His subtle dysmorphic facial features and mild intellectual impairment were suspected for chromosome 22q11.2 deletion syndrome. The diagnosis was confirmed by fluorescence in situ hybridization, which found microdeletion in 22q11.2 region. The characteristic facial appearance can lead to clinical suspicion of this syndrome. The case report emphasizes that this syndrome is not uncommon and presents as a remarkable variability in the severity and extent of expression. Accurate diagnosis is important for genetic counseling and long-term health supervision by multidisciplinary team.

  3. 22q11.2 rearrangements found in women with low ovarian reserve and premature ovarian insufficiency.

    Science.gov (United States)

    Jaillard, Sylvie; Tucker, Elena J; Akloul, Linda; Beaumont, Marion; Domin, Mathilde; Pasquier, Laurent; Jouve, Guilhem; Odent, Sylvie; Belaud-Rotureau, Marc-Antoine; Ravel, Célia

    2018-03-14

    Ovarian reserve represents the number of available follicles/oocytes within ovaries and it can be assessed by follicle stimulating hormone levels, anti-Müllerian hormone levels, and/or antral follicle count determined by ultrasounds. A low ovarian reserve is defined by an abnormal ovarian reserve test. This condition can be considered premature if it occurs before the age of 40, leading to premature ovarian insufficiency. Despite the growing knowledge concerning the genetic basis of ovarian deficiency, the majority of cases remain without a genetic diagnosis. Although 22q11.2 deletions and duplications have been associated with genitourinary malformations, ovarian deficiency is not a commonly reported feature. We report here four patients bearing a 22q11.2 rearrangement, identified during the clinical assessment of their low ovarian reserve or premature ovarian insufficiency, and discuss the molecular basis of the ovarian defects.

  4. A Case of Microdeletion in 22q11.2 in a patient with schizophrenia, mental retardation and diabetes

    Directory of Open Access Journals (Sweden)

    Nuno Borja-Santos

    2014-10-01

    Full Text Available The authors describe a case of a 31 year old female patient, who experienced at the age of 26 a sudden onset of schizophrenia, diagnosed by DSM-IV and ICD-10 criteria. She was treated with haloperidol, but after a second outburst at the age of 27 she was switched to risperidone. At the age of 28, she was diagnosed with insulin-dependent diabetes mellitus. Because she had several malformations - usually reported in velo-cardio-facial syndrome (VCFS - the authors decided to perform an analysis of chromosome 22, at 22q11.2, since this region has been associated with VCFS and schizophrenia. The result was a microdeletion observed at 22q11.2. The authors discuss the clinical and genetic implications of this finding, in what concerns schizophrenia, velo-cardio-facial syndrome and diabetes mellitus.

  5. Behavioral abnormalities are common and severe in patients with distal 22q11.2 microdeletions and microduplications.

    Science.gov (United States)

    Lindgren, Valerie; McRae, Anne; Dineen, Richard; Saulsberry, Alexandria; Hoganson, George; Schrift, Michael

    2015-07-01

    We describe six individuals with microdeletions and microduplications in the distal 22q11.2 region detected by microarray. Five of the abnormalities have breakpoints in the low-copy repeats (LCR) in this region and one patient has an atypical rearrangement. Two of the six patients with abnormalities in the region between LCR22 D-E have hearing loss, which has previously been reported only once in association with these abnormalities. We especially note the behavioral/neuropsychiatric problems, including the severity and early onset, in patients with distal 22q11.2 rearrangements. Our patients add to the genotype-phenotype correlations which are still being generated for these chromosomal anomalies.

  6. Congenital diaphragmatic hernia in Smith-Magenis syndrome: a possible locus at chromosome 17p11.2.

    Science.gov (United States)

    Sanford, E F; Bermudez-Wagner, K; Jeng, L J B; Rauen, K A; Slavotinek, Anne M

    2011-11-01

    We report on a 7-month-old girl with Smith-Magenis syndrome (SMS) due to a 4.76-Mb deletion of 17p12-17p11.2 detected by array comparative genomic hybridization. She was also affected with a left-sided congenital diaphragmatic hernia (CDH) and cardiac anomalies including an atypical atrioventricular canal defect and a cleft mitral valve. To our knowledge, this is the first reported case of a patient with both SMS and CDH. There are numerous chromosomal regions in which duplications, deletions, inversions, or translocations have been associated with CDH, but none have previously been reported at or close to 17p11.2. We discuss candidate genes for the diaphragmatic defect in this patient. Our case demonstrates that it is important to consider the possibility of SMS in non-isolated cases of diaphragmatic hernia. Copyright © 2011 Wiley Periodicals, Inc.

  7. Cutaneous metastases during an aggressive course of Xp11.2 translocation renal cell carcinoma in a teenager.

    Science.gov (United States)

    Sudour-Bonnange, Helene; Leroy, Xavier; Chauvet, Marie-Pierre; Classe, Marion; Robin, P M; Leblond, Pierre

    2014-09-01

    We reported a rare case of cutaneous metastases of renal cell carcinoma (RCC) with an Xp11.2 translocation in a 15-year-old female. Clinicians should be aware of the possibility of this uncommon site of metastasis, which can indicate multivisceral dissemination of the disease. We discuss the feasibility and opportunity of treating such a patient with multiple line of tyrosine kinase inhibitor (TKI) targeting vascular endothelial and platelet-derived growth factor receptors. © 2014 Wiley Periodicals, Inc.

  8. Systematic of signature inversion in (h11/2)p ⊗ (i13/2)n for odd–odd ...

    Indian Academy of Sciences (India)

    11. /2)p. ⊗. (i13. /2)n. }fo r rare earth s are rep o rted . Each b o x lists th e fo llowin g in fo rmatio n. : T o p row. : K. (observed),. Ic. (inversion),. M iddle row. : K and confi guratio n fro m systematic,. B otto m row. : low est observed spin and its energy in. keV . xxx denotes unknow n energy. C onfi gurations are abbrev iated as:p.

  9. Obstructive sleep apnea syndrome in children with 22q11.2 deletion syndrome after operative intervention for velopharyngeal insufficiency

    Directory of Open Access Journals (Sweden)

    David Jeffrey Crockett

    2014-08-01

    Full Text Available Introduction: Surgical treatment of velopharyngeal insufficiency (VPI in 22q11.2 deletion syndrome is often warranted. In this patient population, VPI is characterized by poor palatal elevation and muscular hypotonia with an intact palate. We hypothesize that 22q11.2 deletion patients are at greater risk of obstructive sleep apnea (OSA after surgical correction of VPI, due, in part, to their functional hypotonia, large velopharyngeal gap size, and the need to surgically obstruct the velopharynx. Methods: We performed a retrospective analysis of patients with 22q11.2 deletion syndrome treated at a tertiary pediatric hospital between the years of 2002-2012. The incidence of VPI, need for surgery, post-operative polysomnogram, post-operative VPI assessment, and OSA treatments were evaluated. Results: Forty-three patients (18 males, 25 females, ages 1-14 years fitting the inclusion criteria were identified. Twenty-eight patients were evaluated by speech pathology due to hypernasality. Twenty-one patients had insufficient velopharyngeal function and required surgery. Fifteen underwent pharyngeal flap surgery, three underwent sphincter pharyngoplasty, two underwent Furlow palatoplasty, and one underwent combined sphincter pharyngoplasty with Furlow palatoplasty. Of these, eight had post-operative snoring. Six of these underwent polysomnography. Four patients were found to have OSA based on the results of the polysomnography (average apnea/hypopnea index of 4.9 events/hour, median=5.1, SD=2.1. Two required continuous positive airway pressure (CPAP due to moderate OSA.Conclusion: Surgery is often necessary to correct VPI in patients with 22q11.2 deletion syndrome. Monitoring for OSA should be considered after surgical correction of VPI due to a high occurrence in this population. Furthermore, families should be counseled of the risk of OSA after surgery and the potential need for treatment with CPAP.

  10. Exercise Performance and 22q11.2 Deletion Status Affect Quality of Life in Tetralogy of Fallot.

    Science.gov (United States)

    Goldmuntz, Elizabeth; Cassedy, Amy; Mercer-Rosa, Laura; Fogel, Mark A; Paridon, Stephen M; Marino, Bradley S

    2017-10-01

    To identify mediators of health status and quality of life (QOL) in children and adolescents aged 8-18 years old following surgical repair for tetralogy of Fallot (TOF), including resource use, exercise performance, and 22q11.2 deletion status. We performed a corollary study to a cross-sectional analysis of subjects following repair for TOF that completed cardiac magnetic resonance imaging, cardiopulmonary exercise tests, and instruments assessing health status and QOL. General linear models were used to test for mediation. A total of 29 of 151 (19%) patients carried a 22q11.2 deletion. Parents of children with a deletion compared with those without a deletion reported worse physical and psychosocial functioning on the Child Health Questionnaire. The patients with a 22q11.2 deletion and their parents reported lower total and Disease Impact scores compared with the group without a deletion on the Pediatric Cardiac Quality of Life Inventory. Medical care use negatively correlated with measures of health status/QOL. Greater maximum work correlated with better patient health status and QOL, regardless of deletion status. Exercise performance mediated the association between deletion status and parent-reported outcomes (unstandardized effects ranging from 2.4 to 4.2) and patient-reported Disease Impact (0.99; 95% CI 0.02-2.70). Children and adolescents following repair for TOF seem to suffer significant challenges to their health status and QOL, which is amplified markedly in the context of the 22q11.2 deletion syndrome, and related to exercise performance. Copyright © 2017. Published by Elsevier Inc.

  11. Autosomal dominant {open_quotes}Opitz{close_quotes} GBBB syndrome due to a 22q11.2 deletion

    Energy Technology Data Exchange (ETDEWEB)

    McDonald-McGinn, D.M.; Emanuel, B.S.; Zackai, E.H. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)

    1996-08-23

    The classification of Opitz GBBB syndrome has been associated with the deletion of the DiGeorge chromosome region on human chromosome 22q11.2. The broad phenotype involved in this deletion syndrome has been referred to as the DiGeorge/velocardiofacial syndrome. The clinical description of the patient will influence the diagnosis of the syndrome. More cooperation between the clinicians and the molecular researchers is necessary in order to locate the gene(s) for these disorders. 11 refs.

  12. Detection of microdeletion 22q11.2 in a fetus by next-generation sequencing of maternal plasma.

    Science.gov (United States)

    Jensen, Taylor J; Dzakula, Zeljko; Deciu, Cosmin; van den Boom, Dirk; Ehrich, Mathias

    2012-07-01

    Efforts have been undertaken recently to assess the fetal genome through analysis of circulating cell-free (ccf) fetal DNA obtained from maternal plasma. Sequencing analysis of such ccf DNA has been shown to enable accurate prenatal detection of fetal aneuploidies, including trisomies of chromosomes 21, 18, and 13. We sought to extend these analyses to examine subchromosomal copy number variants through the sequencing of ccf DNA. We examined a clinically relevant genomic region, chromosome 22q11.2, the location of a series of well-characterized deletion anomalies that cause 22q11.2 deletion syndrome. We sequenced ccf DNA isolated from maternal plasma samples obtained from 2 patients with confirmed 22q11.2 deletion syndrome and from 14 women at low risk for fetal chromosomal abnormalities. The latter samples were used as controls, and the mean genomic coverage was 3.83-fold. Data were aligned to the human genome, repetitive regions were removed, the remaining data were normalized for GC content, and z scores were calculated for the affected region. The median fetal DNA contribution for all samples was 18%, with the affected samples containing 17%-18% fetal DNA. Using a technique similar to that used for sequencing-based fetal aneuploidy detection from maternal plasma, we detected a statistically significant loss of representation of a portion of chromosome 22q11.2 in both of the affected fetal samples. No such loss was detected in any of the control samples. Noninvasive prenatal diagnosis of subchromosomal fetal genomic anomalies is feasible with next-generation sequencing.

  13. Systematic of signature inversion in (h11/2)p ⊗ (i13/2)n for odd–odd ...

    Indian Academy of Sciences (India)

    rotational properties of a wave function, it follows that α = 0 for even-angular momentum states of a rotational band and α = 1 for odd-angular momentum states. We have analysed the (h11/2)p ⊗ ( i13/2)n orbitals of double-odd nuclei in rare-earth region. The favoured signature in odd–odd rotational bands is given by αf ...

  14. Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiao; Zhou, Hao; Duan, Na; Liu, Yongkang; Wang, Zhongqiu [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Zhu, Qingqiang [Medical School of Yangzhou University, Department of Medical Imaging, Subei People' s Hospital, Yangzhou (China); Li, Baoxin [Gulou Hospital, Department of Radiology, Nanjing (China); Cui, Wenjing [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Nanjing University Medical School, Department of Radiology, Jinling Hospital, Nanjing (China); Kundra, Vikas [The University of Texas, M.D. Anderson Cancer Center, Department of Radiology, Houston, TX (United States)

    2017-02-15

    To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. (orig.)

  15. Screening for Mutations in the TBX1 Gene on Chromosome 22q11.2 in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Lieh-Yung Ping

    2016-11-01

    Full Text Available A higher-than-expected frequency of schizophrenia in patients with 22q11.2 deletion syndrome suggests that chromosome 22q11.2 harbors the responsive genes related to the pathophysiology of schizophrenia. The TBX1 gene, which maps to the region on chromosome 22q11.2, plays a vital role in neuronal functions. Haploinsufficiency of the TBX1 gene is associated with schizophrenia endophenotype. This study aimed to investigate whether the TBX1 gene is associated with schizophrenia. We searched for mutations in the TBX1 gene in 652 patients with schizophrenia and 567 control subjects using a re-sequencing method and conducted a reporter gene assay. We identified six SNPs and 25 rare mutations with no association with schizophrenia from Taiwan. Notably, we identified two rare schizophrenia-specific mutations (c.-123G>C and c.-11delC located at 5′ UTR of the TBX1 gene. The reporter gene assay showed that c.-123C significantly decreased promoter activity, while c.-11delC increased promoter activity compared with the wild-type. Our findings suggest that the TBX1 gene is unlikely a major susceptible gene for schizophrenia in an ethnic Chinese population for Taiwan, but a few rare mutations in the TBX1 gene may contribute to the pathogenesis of schizophrenia in some patients.

  16. Prenatal Screening for 22q11.2 Deletion Using a Targeted Microarray-Based Cell-Free DNA Test.

    Science.gov (United States)

    Schmid, Maximilian; Wang, Eric; Bogard, Patrick E; Bevilacqua, Elisa; Hacker, Coleen; Wang, Susie; Doshi, Jigna; White, Karen; Kaplan, Jennifer; Sparks, Andrew; Jani, Jacques C; Stokowski, Renee

    2017-11-08

    To determine the performance of a targeted microarray-based cell-free DNA (cfDNA) test (Harmony Prenatal Test®) for the identification of pregnancies at increased risk for 22q11.2 deletion. Test performance was determined in 2 steps including a total of 1,953 plasma samples. Analytical validation was performed in 1,736 plasma samples. Clinical verification of performance was performed in an additional 217 prospectively ascertained samples from pregnancies with fetal deletion status determined by diagnostic testing. Analytical sensitivity was 75.4% (95% CI: 67.1-82.2%) based on 122 samples with deletions ranging from 1.96 to 3.25 Mb. In 1,614 presumed unaffected samples, specificity was determined to be at least 99.5% (95% CI: 99.0-99.7%). In the clinical cohort, 5 of 7 samples from pregnancies affected with 22q11.2 deletion were determined to have a high probability of deletion. There were no false positive results in the 210 unaffected samples in this cohort. These clinical data are consistent with the performance demonstrated in the analytical validation. cfDNA testing using a targeted microarray-based technology is able to identify pregnancies at increased risk for 22q11.2 deletions of 3.0 Mb and smaller while maintaining a low false positive rate. © 2017 S. Karger AG, Basel.

  17. [Phenotypic and genotypic analysis of a fetus carrying an intermediate 22q11.2 deletion encompassing the CRKL gene].

    Science.gov (United States)

    Lin, Shaobin; Zheng, Xiaohe; Gu, Heng; Li, Mingzhen

    2017-06-10

    To delineate the phenotypic characteristics of 22q11.2 deletion syndrome and the role of CRKL gene in the pathogenesis of cardiac abnormalities. G-banded karyotyping, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization (FISH) were performed on a fetus with tetralogy of Fallot detected by ultrasound. Correlation between the genotype and phenotype was explored after precise mapping of the breakpoints on chromosome 22q11.2. SNP array was also performed on peripheral blood samples from both parents to clarify its origin. The fetus showed a normal karyotype of 46,XY. SNP array performed on fetal blood sample revealed a 749 kb deletion (chr22: 20 716 876-21 465 659) at 22q11.21, which encompassed the CRKL gene but not TBX1, HIRA, COMT and MAPK1. Precise mapping of the breakpoints suggested that the deleted region has overlapped with that of central 22q11.2 deletion syndrome. SNP array analysis of the parental blood samples suggested that the 22q11.21 deletion has a de novo origin. The presence of 22q11.21 deletion in the fetus was also confirmed by FISH analysis. Central 22q11.21 deletion probably accounts for the cardiac abnormalities in the fetus, for which the CRKL gene should be considered as an important candidate.

  18. Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.

    Science.gov (United States)

    Mlynarski, Elisabeth E; Xie, Michael; Taylor, Deanne; Sheridan, Molly B; Guo, Tingwei; Racedo, Silvia E; McDonald-McGinn, Donna M; Chow, Eva W C; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J; Roberts, Amy E; Piotrowicz, Małgorzata; Bearden, Carrie E; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Goldmuntz, Elizabeth; Bassett, Anne S; Morrow, Bernice E; Emanuel, Beverly S

    2016-03-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60-75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients.

  19. The Identification of Microdeletion and Reciprocal Microduplication in 22q11.2 Using High-Resolution CMA Technology

    Directory of Open Access Journals (Sweden)

    Ana Julia Cunha Leite

    2016-01-01

    Full Text Available The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal Microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications.

  20. Screening for Mutations in the TBX1 Gene on Chromosome 22q11.2 in Schizophrenia.

    Science.gov (United States)

    Ping, Lieh-Yung; Chuang, Yang-An; Hsu, Shih-Hsin; Tsai, Hsin-Yao; Cheng, Min-Chih

    2016-11-22

    A higher-than-expected frequency of schizophrenia in patients with 22q11.2 deletion syndrome suggests that chromosome 22q11.2 harbors the responsive genes related to the pathophysiology of schizophrenia. The TBX1 gene, which maps to the region on chromosome 22q11.2, plays a vital role in neuronal functions. Haploinsufficiency of the TBX1 gene is associated with schizophrenia endophenotype. This study aimed to investigate whether the TBX1 gene is associated with schizophrenia. We searched for mutations in the TBX1 gene in 652 patients with schizophrenia and 567 control subjects using a re-sequencing method and conducted a reporter gene assay. We identified six SNPs and 25 rare mutations with no association with schizophrenia from Taiwan. Notably, we identified two rare schizophrenia-specific mutations (c.-123G>C and c.-11delC) located at 5' UTR of the TBX1 gene. The reporter gene assay showed that c.-123C significantly decreased promoter activity, while c.-11delC increased promoter activity compared with the wild-type. Our findings suggest that the TBX1 gene is unlikely a major susceptible gene for schizophrenia in an ethnic Chinese population for Taiwan, but a few rare mutations in the TBX1 gene may contribute to the pathogenesis of schizophrenia in some patients.

  1. Evidence for altered hippocampal function in a mouse model of the human 22q11.2 microdeletion.

    Science.gov (United States)

    Drew, Liam J; Stark, Kimberly L; Fénelon, Karine; Karayiorgou, Maria; Macdermott, Amy B; Gogos, Joseph A

    2011-08-01

    22q11.2 chromosomal deletions are recurrent copy number mutations that increase the risk of schizophrenia around thirty-fold. Deletion of the orthologous chromosomal region in mice offers an opportunity to characterize changes to neuronal structure and function that may account for the development of this disease. The hippocampus has been implicated in schizophrenia pathogenesis, is reduced in volume in 22q11.2 deletion carriers and displays altered neuronal structure in a mouse model of the mutation (Df(16)A(+/-) mice). Here we investigate hippocampal CA1 physiology, hippocampal-dependent spatial memory and novelty-induced hippocampal activation in Df(16)A(+/-) mice. We found normal spatial reference memory (as assayed by the Morris water maze test) as well as modest but potentially important deficits in physiology. In particular, a reduction in the level of inhibition of CA1 pyramidal neurons was observed, implying a decrease in interneuron activity. Additionally, deficits in LTP were observed using certain induction protocols. Induction of c-Fos expression by exploration of a novel environment suggested a relative sparing of CA1 and dentate gyrus function but showed a robust decrease in the number of activated CA3 pyramidal neurons in Df(16)A(+/-) mice. Overall, experiments performed in this 22q11.2 deletion model demonstrated deficits of various degrees across different regions of the hippocampus, which together may contribute to the increased risk of developing schizophrenia. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. The 22q11.2 microdeletion: fifteen years of insights into the genetic and neural complexity of psychiatric disorders.

    Science.gov (United States)

    Drew, Liam J; Crabtree, Gregg W; Markx, Sander; Stark, Kimberly L; Chaverneff, Florence; Xu, Bin; Mukai, Jun; Fenelon, Karine; Hsu, Pei-Ken; Gogos, Joseph A; Karayiorgou, Maria

    2011-05-01

    Over the last fifteen years it has become established that 22q11.2 deletion syndrome (22q11DS) is a true genetic risk factor for schizophrenia. Carriers of deletions in chromosome 22q11.2 develop schizophrenia at rate of 25-30% and such deletions account for as many as 1-2% of cases of sporadic schizophrenia in the general population. Access to a relatively homogeneous population of individuals that suffer from schizophrenia as the result of a shared etiological factor and the potential to generate etiologically valid mouse models provides an immense opportunity to better understand the pathobiology of this disease. In this review we survey the clinical literature associated with the 22q11.2 microdeletions with a focus on neuroanatomical changes. Then, we highlight results from work modeling this structural mutation in animals. The key biological pathways disrupted by the mutation are discussed and how these changes impact the structure and function of neural circuits is described. Copyright © 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. The Identification of Microdeletion and Reciprocal Microduplication in 22q11.2 Using High-Resolution CMA Technology.

    Science.gov (United States)

    Leite, Ana Julia Cunha; Pinto, Irene Plaza; Cunha, Damiana Mirian da Cruz E; Ribeiro, Cristiano Luiz; da Silva, Claudio Carlos; da Cruz, Aparecido Divino; Minasi, Lysa Bernardes

    2016-01-01

    The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal Microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications.

  4. INTERPRETING THE SUBTLE SPECTRAL VARIATIONS OF THE 11.2 AND 12.7 μ m POLYCYCLIC AROMATIC HYDROCARBON BANDS

    Energy Technology Data Exchange (ETDEWEB)

    Shannon, M. J.; Stock, D. J.; Peeters, E., E-mail: mshann3@uwo.ca [Department of Physics and Astronomy, University of Western Ontario, London, ON, N6A 3K7 (Canada)

    2016-06-20

    We report new properties of the 11 and 12.7 μ m emission complexes of polycyclic aromatic hydrocarbons (PAHs) by applying a Gaussian-based decomposition technique. Using high-resolution Spitzer Space Telescope data, we study in detail the spectral and spatial characteristics of the 11 and 12.7 μ m emission bands in maps of reflection nebulae NGC 7023 and NGC 2023 (north and south) and the star-forming region M17. Profile variations are observed in both the 11 and 12.7 μ m emission bands. We identify a neutral contribution to the traditional 11.0 μ m PAH band and a cationic contribution to the traditional 11.2 μ m band, the latter of which affects the PAH class of the 11.2 μ m emission in our sample. The peak variations of the 12.7 μ m complex are explained by the competition between two underlying blended components. The spatial distributions of these components link them to cations and neutrals. We conclude that the 12.7 μ m emission originates in both neutral and cationic PAHs, lending support to the use of the 12.7/11.2 intensity ratio as a charge proxy.

  5. Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

    DEFF Research Database (Denmark)

    Delio, Maria; Guo, Tingwei; McDonald-McGinn, Donna M

    2013-01-01

    Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications....... Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11......DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting...

  6. Two patients with duplication of 17p11.2: The reciprocal of the Smith-Magenis syndrome deletion?

    Energy Technology Data Exchange (ETDEWEB)

    Brown, A. [Greenwood Genetic Center, SC (United States)]|[Clemson Univ., SC (United States); Phelan, M.C.; Rogers, R.C. [Greenwood Genetic Center, SC (United States)] [and others

    1996-05-17

    J.M. and H.G. are two unrelated male patients with developmental delay. Cytogenetic analysis detected a duplication of 17p11.2 in both patients. The extent of the duplicated region was determined using single copy DNA probes: cen-D17S58-D17S29-D17S258-D17S71-D17S445-D17S122-tel. Four of the six markers, D17S29, D17S258, D17S71, and D17S445, were duplicated by dosage analysis. Fluorescent in situ hybridization (FISH) analysis of H.G., using cosmids for locus D17S29, confirmed the duplication in 17p11.2. Because the deletion that causes the Smith-Magenis syndrome involves the same region of 17p11.2 as the duplication in these patients, the mechanism may be similar to that proposed for the reciprocal deletion/ duplication event observed in Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and Charcot-Marie-Tooth Type 1A disease (CMT1A). 30 refs., 3 figs., 1 tab.

  7. Analysis of 22q11.2 deletions by FISH in a series of velocardiofacial syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Ravnan, J.B.; Golabi, M.; Lebo, R.V. [Univ. of California, San Francisco, CA (United States)

    1994-09-01

    Deletions in chromosome 22 band q11.2 have been associated with velocardiofacial (VCF or Shprintzen) syndrome and the DiGeorge anomaly. A study of VCF patients evaluated at the UCSF Medical Center was undertaken to correlate disease phenotype with presence or absence of a deletion. Patients referred for this study had at least two of the following: dysmorphic facial features, frequent ear infections or hearing loss, palate abnormalities, thymic hypoplasia, hypocalcemia, congenital heart defect, hypotonia, and growth or language delay. Fluorescence in situ hybridization (FISH) using the DiGeorge critical region probe N25 was used to classify patients according to the presence or absence of a deletion in 22q11.2, and the results were compared to clinical characteristics. We have completed studies on 58 patients with features of VCF. Twenty-one patients (36%) were found to have a deletion in 22q11.2 by FISH. A retrospective study of archived slides from 14 patients originally studied only by prometaphase GTG banding found six patients had a deletion detected by FISH; of these, only two had a microscopically visible chromosome deletion. Our study of 11 sets of parents of children with the deletion found two clinically affected mothers with the deletion, including one with three of three children clinically affected. A few patients who did not fit the classical VCF description had a 22q11.2 deletion detected by FISH. These included one patient with both cleft lip and palate, and another with developmental delay and typical facial features but no cardiac or palate abnormalities. Both patients with the DiGeorge anomaly as part of VCF had the deletion. On the other hand, a number of patients diagnosed clinically with classical VCF did not have a detectable deletion. This raises the question whether they represent a subset of patients with a defect of 22q11.2 not detected by the N25 probe, or whether they represent a phenocopy of VCF.

  8. Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Starnawska, A; Hansen, C S; Sparsø, T; Mazin, W; Olsen, L; Bertalan, M; Buil, A; Bybjerg-Grauholm, J; Bækvad-Hansen, M; Hougaard, D M; Mortensen, P B; Pedersen, C B; Nyegaard, M; Werge, T; Weinsheimer, S

    2017-08-29

    Individuals with 22q11.2 deletion syndrome (DS) have an increased risk of comorbid mental disorders including schizophrenia, attention deficit hyperactivity disorder, depression, as well as intellectual disability. Although most 22q11.2 deletion carriers have the long 3-Mb form of the hemizygous deletion, there remains a large variation in the development and progression of psychiatric disorders, which suggests that alternative factors contribute to the pathogenesis. In this study we investigated whether neonatal DNA methylation signatures in individuals with the 22q11.2 deletion associate with mental disorder later in life. DNA methylation was measured genome-wide from neonatal dried blood spots in a cohort of 164 individuals with 22q11.2DS, including 48 individuals diagnosed with a psychiatric disorder. Among several CpG sites with P-value<10 -6 , we identified cg23546855 (P-value=2.15 × 10 -7 ) mapping to STK32C to be associated with a later psychiatric diagnosis. Pathway analysis of the top findings resulted in the identification of several Gene Ontology pathways to be significantly enriched (P-value<0.05 after Benjamini-Hochberg correction); among them are the following: neurogenesis, neuron development, neuron projection development, astrocyte development, axonogenesis and axon guidance. In addition, we identified differentially methylated CpG sites in LRP2BP (P-value=5.37 × 10 -8 ) to be associated with intellectual disability (F70-79), in TOP1 (P-value=1.86 × 10 -7 ) with behavioral disorders (F90-98), in NOSIP (P-value=5.12 × 10 -8 ) with disorders of psychological development (F80-89) and in SEMA4B (P-value=4.02 × 10 -7 ) with schizophrenia spectrum disorders (F20-29). In conclusion, our study suggests an association of DNA methylation differences at birth with development of mental disorder later in life in 22q11.2DS individuals.

  9. Sequence of pNL194, a 79.3-Kilobase IncN Plasmid Carrying the blaVIM-1 Metallo-β-Lactamase Gene in Klebsiella pneumoniae▿

    Science.gov (United States)

    Miriagou, V.; Papagiannitsis, C. C.; Kotsakis, S. D.; Loli, A.; Tzelepi, E.; Legakis, N. J.; Tzouvelekis, L. S.

    2010-01-01

    The nucleotide sequence of pNL194, a VIM-1-encoding plasmid, is described in this study. pNL194 (79,307 bp) comprised an IncN-characteristic segment (38,940 bp) and a mosaic structure (40,367 bp) including blaVIM-1, aacA7, aadA1, aadA2, dfrA1, dfrA12, aphA1, strA, strB, and sul1. Tn1000 or Tn5501 insertion within fipA probably facilitated recruitment of additional mobile elements carrying resistance genes. PMID:20660690

  10. Sequence of pNL194, a 79.3-kilobase IncN plasmid carrying the blaVIM-1 metallo-beta-lactamase gene in Klebsiella pneumoniae.

    Science.gov (United States)

    Miriagou, V; Papagiannitsis, C C; Kotsakis, S D; Loli, A; Tzelepi, E; Legakis, N J; Tzouvelekis, L S

    2010-10-01

    The nucleotide sequence of pNL194, a VIM-1-encoding plasmid, is described in this study. pNL194 (79,307 bp) comprised an IncN-characteristic segment (38,940 bp) and a mosaic structure (40,367 bp) including bla(VIM-1), aacA7, aadA1, aadA2, dfrA1, dfrA12, aphA1, strA, strB, and sul1. Tn1000 or Tn5501 insertion within fipA probably facilitated recruitment of additional mobile elements carrying resistance genes.

  11. An Adult Case of Chromosome 22q11.2 Deletion Syndrome Associated with a High-positioned Right Aortic Arch.

    Science.gov (United States)

    Hoshino, Yoichi; Machida, Moriya; Shimano, Shun-Ichi; Taya, Teizo

    2017-01-01

    Chromosome 22q11.2 deletion syndrome (22q11.2 DS) has a very wide phenotypic spectrum that includes dysmorphic features, cardiac anomalies, and hypocalcemia arising from hypoparathyroidism. We herein describe an adult case of 22q11.2 DS with associated hypoparathyroidism and anomalies of the aortic arch. Because the patient had been diagnosed with primary hypoparathyroidism at another hospital, a diagnosis of 22q11.2 DS had been overlooked. A chest X-ray examination revealed widening of the mediastinum caused by a high-positioned right aortic arch, and we subsequently confirmed a diagnosis of 22q11.2 DS using fluorescence in situ hybridization. Because primary hypoparathyroidism is a rare disorder, physicians should be aware of the variable phenotypic features of 22q11.2 DS.

  12. Genetic variants at 1p11.2 and breast cancer risk: a two-stage study in Chinese women.

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    Yue Jiang

    Full Text Available BACKGROUND: Genome-wide association studies (GWAS have identified several breast cancer susceptibility loci, and one genetic variant, rs11249433, at 1p11.2 was reported to be associated with breast cancer in European populations. To explore the genetic variants in this region associated with breast cancer in Chinese women, we conducted a two-stage fine-mapping study with a total of 1792 breast cancer cases and 1867 controls. METHODOLOGY/PRINCIPAL FINDINGS: Seven single nucleotide polymorphisms (SNPs including rs11249433 in a 277 kb region at 1p11.2 were selected and genotyping was performed by using TaqMan® OpenArray™ Genotyping System for stage 1 samples (878 cases and 900 controls. In stage 2 (914 cases and 967 controls, three SNPs (rs2580520, rs4844616 and rs11249433 were further selected and genotyped for validation. The results showed that one SNP (rs2580520 located at a predicted enhancer region of SRGAP2 was consistently associated with a significantly increased risk of breast cancer in a recessive genetic model [Odds Ratio (OR  =  1.66, 95% confidence interval (CI  =  1.16-2.36 for stage 2 samples; OR  =  1.51, 95% CI  =  1.16-1.97 for combined samples, respectively]. However, no significant association was observed between rs11249433 and breast cancer risk in this Chinese population (dominant genetic model in combined samples: OR  =  1.20, 95% CI  =  0.92-1.57. CONCLUSIONS/SIGNIFICANCE: Genotypes of rs2580520 at 1p11.2 suggest that Chinese women may have different breast cancer susceptibility loci, which may contribute to the development of breast cancer in this population.

  13. A rare duplication on chromosome 16p11.2 is identified in patients with psychosis in Alzheimer's disease.

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    Xiaojing Zheng

    Full Text Available Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652 was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46% was similar to that reported previously in schizophrenia (0.46%. This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ, and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis.

  14. Disentangling resting-state BOLD variability and PCC functional connectivity in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Zöller, Daniela; Schaer, Marie; Scariati, Elisa; Padula, Maria Carmela; Eliez, Stephan; Van De Ville, Dimitri

    2017-04-01

    Although often ignored in fMRI studies, moment-to-moment variability of blood oxygenation level dependent (BOLD) signals reveals important information about brain function. Indeed, higher brain signal variability has been associated with better cognitive performance in young adults compared to children and elderly adults. Functional connectivity, a very common approach in resting-state fMRI analysis, is scaled for variance. Thus, alterations might be confounded or driven by BOLD signal variance alterations. Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurodevelopmental disorder that is associated with a vast cognitive and clinical phenotype. To date, several resting-state fMRI studies reported altered functional connectivity in 22q11.2DS, however BOLD signal variance has not yet been analyzed. Here, we employed PLS correlation analysis to reveal multivariate patterns of diagnosis-related alterations and age-relationship throughout the cortex of 50 patients between 9 and 25 years old and 50 healthy controls in the same age range. To address how functional connectivity in the default mode network is influenced by BOLD signal fluctuations, we conducted the same analysis on seed-to-voxel connectivity of the posterior cingulate cortex (PCC) and compared resulting brain patterns. BOLD signal variance was lower mainly in regions of the default mode network and in the dorsolateral prefrontal cortex, but higher in large parts of the temporal lobes. In those regions, BOLD signal variance was correlated with age in healthy controls, but not in patients, suggesting deviant developmental trajectories from child- to adulthood. Positive connectivity of the PCC within the default mode network as well as negative connectivity towards the frontoparietal network were weaker in patients with 22q11.2DS. We furthermore showed that lower functional connectivity of the PCC was not driven by higher BOLD signal variability. Our results confirm the strong implication of BOLD

  15. The gene encoding human glutathione synthetase (GSS) maps to the long arm of chromosome 20 at band 11.2

    Energy Technology Data Exchange (ETDEWEB)

    Webb, G.C.; Vaska, V.L.; Ford, J.H. [Queen Elizabeth Hospital, Woodville (Australia)] [and others

    1995-12-10

    Two forms of glutathione synthetase deficiency have been described. While one form is mild, causing hemolytic anemia, the other more severe form causes 5-oxoprolinuria with secondary neurological involvement. Despite the existence of two deficiency phenotypes, Southern blots hybridized with a glutathione synthetase cDNA suggest that there is a single glutathione synthetase gene in the human genome. Analysis of somatic cell hybrids showed the human glutathione synthetase gene (GSS) to be located on chromosome 20, and this assignment has been refined to subband 20q11.2 using in situ hybridization. 16 refs., 2 figs.

  16. Otozomal dominat geçişin görüldüğü ailesel 22q11.2 delesyon sendromu

    OpenAIRE

    Göktürk, Bahar; Gökdemir, Mahmut; Reisli, İsmail; Yıldırım, Mahmut

    2016-01-01

    22q11.2 deletion syndrome is the most frequent microdeletion syndrome in humans and caused by hemizygote deletion on only one chromosome. Most of probands have a de novo deletion of 22q11.2, but 8-20% have inherited the 22q11.2 deletion from a parent (autosomal dominant mutation). Genotype-phenotype correlation is weak in this patient group. We aimed to present three members in the same family due to an autosomal dominant inheritance with 22q11.2 deletion and different clinical findings. [Cuk...

  17. Correction: Forrester, N.L.; Coffey, L.L.; Weaver, S.C. Arboviral Bottlenecks and Challenges to Maintaining Diversity and Fitness during Mosquito Transmission. Viruses 2014, 6, 3991–4004

    Directory of Open Access Journals (Sweden)

    Naomi L. Forrester

    2014-11-01

    Full Text Available In the original manuscript, Forrester, N.L.; Coffey, L.L.; Weaver, S.C. Arboviral Bottlenecks and Challenges to Maintaining Diversity and Fitness during Mosquito Transmission. Viruses 2014, 6, 3991–4004, Figure 1 contains an error, the third bottle was absent from the figure:[...

  18. Expanding the BP1-BP2 15q11.2 Microdeletion Phenotype: Tracheoesophageal Fistula and Congenital Cataracts

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    D. Wong

    2013-01-01

    Full Text Available The proximal q arm of chromosome 15 contains breakpoint regions BP1–BP5 with the classic deletion of BP1–BP3 best known to be associated with Prader-Willi and Angelman syndromes. The region is approximately 500 kb and microdeletions within the BP1-BP2 region have been reported in patients with developmental delay, behavioral abnormalities, and motor apraxia as well as dysmorphic features including hypertelorism, cleft or narrow palate, ear abnormalities, and recurrent upper airway infections. We report two patients with unique, never-before-reported 15q11.2 BP1-2 microdeletion syndrome findings, one with proximal esophageal atresia and distal tracheoesophageal fistula (type C and one with congenital cataracts. Cataracts have been described in Prader-Willi syndrome but we could not find any description of cataracts in Angelman syndrome. Esophageal atresia and tracheoesophageal fistula have not been reported to our knowledge in either syndrome. A chance exists that both cases are sporadic birth defects; however, the findings of the concomitant microdeletion cannot be overlooked as a possible cause. Based on our review of the literature and the presentation of our patients, we recommend that esophageal atresia and distal tracheoesophageal fistula as well as congenital cataracts be included in the phenotypic spectrum of 15q11.2 BP1-2 microdeletion syndrome.

  19. Ictus emeticus presenting as an unusual seizure type in chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Hung, Pi-Lien; Huang, Li-Tung; Kwan, Shang-Yeong; Chang, Kai-Ping; Chen, Hsin-Hung; Lee, Yi-Yen; Fan, Hueng-Chuen; Chen, Chien

    2017-03-01

    We present a case study of a patient with chromosome 22q11.2 deletion syndrome presenting with ictus emeticus, together with a review of the relevant literature. The patient developed generalized tonic-clonic seizures at 3 months old, and seizures eventually remitted after calcium therapy. He then experienced vigorous vomiting that occurred during sleep, with glassy eyes and legs flexion. Video-EEG recordings exhibited a switch in background activity from organized reactivity during normal sleep to left lateralized temporal delta activity, which was bilaterally synchronized during an emetic attack. The ictal vomiting ceased following management with oxcarbazepine, high-dose phenobarbital, and a ketogenic diet. The unique seizure type and rare ictal EEG findings are the first reported in a child with chromosome 22q11.2 deletion syndrome. This case highlights that ictus emeticus without detectable epileptic discharge on EEG is one potential epileptic presentation in this genetic syndrome. [Published with video sequence on www.epilepticdisorders.com].

  20. Atypical cortical connectivity and visuospatial cognitive impairments are related in children with chromosome 22q11.2 deletion syndrome

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    Gee James C

    2008-06-01

    Full Text Available Abstract Background Chromosome 22q11.2 deletion syndrome is one of the most common genetic causes of cognitive impairment and developmental disability yet little is known about the neural bases of those challenges. Here we expand upon our previous neurocognitive studies by specifically investigating the hypothesis that changes in neural connectivity relate to cognitive impairment in children with the disorder. Methods Whole brain analyses of multiple measures computed from diffusion tensor image data acquired from the brains of children with the disorder and typically developing controls. We also correlated diffusion tensor data with performance on a visuospatial cognitive task that taps spatial attention. Results Analyses revealed four common clusters, in the parietal and frontal lobes, that showed complementary patterns of connectivity in children with the deletion and typical controls. We interpreted these results as indicating differences in connective complexity to adjoining cortical regions that are critical to the cognitive functions in which affected children show impairments. Strong, and similarly opposing patterns of correlations between diffusion values in those clusters and spatial attention performance measures considerably strengthened that interpretation. Conclusion Our results suggest that atypical development of connective patterns in the brains of children with chromosome 22q11.2 deletion syndrome indicate a neuropathology that is related to the visuospatial cognitive impairments that are commonly found in affected individuals.

  1. Altered neurobiological function of brainstem hypoglossal neurons in DiGeorge/22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Wang, Xin; Bryan, Corey; LaMantia, Anthony-Samuel; Mendelowitz, David

    2017-09-17

    DiGeorge/22q11.2 Deletion Syndrome (22q11DS) is a common genetic microdeletion syndrome that underlies several neurodevelopmental disorders including autism, attention deficit/hyperactivity disorder, and schizophrenia. In addition to cognitive impairments, those with 22q11DS have disrupted feeding and swallowing from birth onward. This perinatal dysphagia significantly compromises nutritional status, impairs appropriate weight gain, and can lead to life threatening aspiration-based infections. Appropriately timed excitation and inhibition of brainstem hypoglossal motor neurons, which innervate tongue muscles, is essential for proper feeding and swallowing. In this study we have examined changes in hypoglossal motor neuron function in the LgDel mouse model of 22q11DS. Hypoglossal motor neurons from LgDel mouse pups have action potentials with afterhyperpolarizations, mediated by a large conductance charybdotoxin-sensitive Ca-activated K current, that are significantly shorter in duration and greater in magnitude than those in wild-type pups. In addition, the amplitude, but not frequency, of glutamatergic excitatory glutamatergic postsynaptic currents (EPSCs) is diminished, and GABAergic, but not glycinergic, neurotransmission to hypoglossal motor neurons was reduced in LgDel animals. These observations provide a foundation for understanding the neurological changes in hypoglossal motor neuron function and their contribution to swallowing abnormalities that occur in DiGeorge/22q11.2 Deletion Syndrome. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations.

    Science.gov (United States)

    Riikonen, Raili Sylvia; Wallden, Tiina; Kokkonen, Hannaleena

    2016-01-01

    Familial cases of West syndrome have been reported only in Japan. In that study no chromosomal analyses were made. It has been suggested that microarray analysis should be included in the diagnostic evaluation of patients with infantile spasms and developmental delay, when an evaluation for structural brain lesions and metabolic disorders reveal no abnormal findings. We report here the first case of infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations. The daughter and mother with infantile spasms, and the autistic son had the duplication. The clinical course of infantile spasms was very similar in the mother and daughter. The spasms were primarily considered to be of unknown aetiology. Chromosomal microarray analysis revealed a 6.2 Mb size 15q11.2q13.1 duplication. The duplication belongs to the 15q11q13 duplication syndrome (OMIM 608636) which when maternally derived is characterised by neuro-behavioural disorders like autism, hypotonia, cognitive deficit, language delay and epilepsy. The proportion of patients with unknown aetiology for infantile spasms will decrease when more careful chromosomal studies are made. Our report expands the phenotype of chromosome 15q duplication syndrome and is the first report of this abnormality in two successive generations of infantile spasms. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. Definition of 5q11.2 Microdeletion Syndrome Reveals Overlap with CHARGE Syndrome and 22q11 Deletion Syndrome Phenotypes

    NARCIS (Netherlands)

    Blok, Charlotte Snijders; Corsten-Janssen, Nicole; FitzPatrick, David R.; Romano, Corrado; Fichera, Marco; Vitello, Girolamo Aurelio; Willemsen, Marjolein H.; Schoots, Jeroen; Pfundt, Rolph; van Ravenswaaij-Arts, Conny M. A.; Hoefsloot, Lies; Kleefstra, Tjitske

    2014-01-01

    Microdeletions of the 5q11.2 region are rare; in literature only two patients with a deletion in this region have been reported so far. In this study, we describe four additional patients and further define this new 5q11.2 microdeletion syndrome. A comparison of the features observed in all six

  4. Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study

    NARCIS (Netherlands)

    Campbell, Linda E.; Daly, Eileen; Toal, Fiona; Stevens, Angela; Azuma, Rayna; Catani, Marco; Ng, Virginia; van Amelsvoort, Therese; Chitnis, Xavier; Cutter, William; Murphy, Declan G. M.; Murphy, Kieran C.

    2006-01-01

    In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of

  5. [Evaluation of detection and analysis of chromosome 22q11.2 microdeletion by multiple ligation-dependent probe amplification assay].

    Science.gov (United States)

    DENG, Jian-ying; ZHANG, Ze-wei; LI, Jian-hua; ZHU, Yu-ning; YANG, Jian-bin; GAO, Zhan; YING, Li-yang

    2011-04-01

    To evaluate multiplex ligation-dependent probe amplification (MLPA) assay detection in analysis of chromosome 22q11.2 microdeletion. Between March 2008 and September 2009, thirty-two patients including 10 males and 16 females aged between years (3.6±3.1) were selected and evaluated by history, physical examination and medical records. Of these patients, sixteen patients who were previous diagnostic as 22q11.2 microdeletion were in positive control group, the other 16 healthy children were in negative control group. All the patients were detected by MLPA and fluorescence in situ hybridization (FISH) for the presence of a 22q11.2 microdeletion after informed consent. Diagnostic efficacy was assessed by sensitivity, specificity and Kappa analysis. We have applied the two assays of detection of chromosome 22q11.2 microdeletion in 32 patients. Sixteen patients in positive control group were found to have a 22q11.2 deletion and, with the deletion size of 3-Mb. However, as expected, chromosome 22q11.2 deletion was not found in negative control group. The MLPA results were in good agreement with that by FISH. Therefore, MLPA has high sensitivity and specificity. MLPA is a rapid, reliable, high-throughput and relatively economical alternative to FISH technology for the diagnosis of 22q11.2 microdeletion. It can provide reliable and helpful information for clinical diagnosis of 22q11.2 microdeletion syndrome.

  6. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1

    NARCIS (Netherlands)

    D.M. Glubb (Dylan); M. Maranian (Melanie); K. Michailidou (Kyriaki); K.A. Pooley (Karen); K.B. Meyer (Kerstin); S. Kar (Siddhartha); A.F.C. Carlebur; M. O'Reilly (Marian); J.A. Betts (Joshua); K.M. Hillman (Kristine); S. Kaufmann (Susanne); J. Beesley (Jonathan); S. Canisius (Sander); J.L. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); M.K. Schmidt (Marjanka); A. Broeks (Annegien); F.B.L. Hogervorst (Frans); C.E. van der Schoot (Ellen); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); P.A. Fasching (Peter); M. Ruebner (Matthias); A.B. Ekici (Arif); M.W. Beckmann (Matthias); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); N. Johnson (Nichola); P.D.P. Pharoah (Paul D.P.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); B. Burwinkel (Barbara); F. Marme (Federick); R. Yang (Rongxi); H. Surowy (Harald); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); R.K. Schmutzler (Rita); H. Brauch (Hiltrud); Y.-D. Ko (Yon-Dschun); T. Brüning (Thomas); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); H. Tanaka (Hideo); T. Dörk (Thilo); N.V. Bogdanova (Natalia); S. Helbig (Sonja); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A.H. Wu (Anna H.); C.-C. Tseng (Chiu-Chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); D. Lambrechts (Diether); H. Zhao (Hui); C. Weltens (Caroline); E. van Limbergen (Erik); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); A. Rudolph (Anja); P. Seibold (Petra); P. Radice (Paolo); P. Peterlongo (Paolo); M. Barile (Monica); F. Capra (Fabio); F.J. Couch (Fergus); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); S.-H. Teo (Soo-Hwang); C.H. Yip (Cheng Har); M.-H. See (Mee-Hoong); B.K. Cornes (Belinda); C-Y. Cheng (Ching-Yu); M.K. Ikram (Kamran); V. Kristensen (Vessela); W. Zheng (Wei); S.L. Halverson (Sandra L.); M. Shrubsole (Martha); J. Long (Jirong); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); K. Czene (Kamila); D. Klevebring (Daniel); H. Darabi (Hatef); M. Eriksson (Mikael); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John W. M.); J.M. Collée (Margriet); P. Hall (Per); J. Li (Jingmei); K. Humphreys (Keith); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y.-T. Gao (Yu-Tang); H. Cai (Hui); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); M. Shah (Mitul); M. Ghoussaini (Maya); D. Kang (Daehee); J.-Y. Choi (J.); S.K. Park (Sue); D-Y. Noh (Dong-Young); M. Hartman (Mikael); X. Miao; W.-Y. Lim (Wei-Yen); A. Tang (Anthony); U. Hamann (Ute); D. Torres (Diana); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); C. Olswold (Curtis); S. Slager (Susan); A.E. Toland (Amanda); D. Yannoukakos (Drakoulis); C-Y. Shen (Chen-Yang); P.-E. Wu (Pei-Ei); J-C. Yu (Jyh-Cherng); M.-F. Hou (Ming-Feng); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Jones (Michael); G. Pita (Guillermo); M.R. Alonso (Rosario); N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); S. Healey (Sue); M. Brown (Melissa); B.A.J. Ponder (Bruce A.J.); G. Chenevix-Trench (Georgia); D. Thompson (Deborah); S.L. Edwards (Stacey); D.F. Easton (Douglas); A.M. Dunning (Alison); J.D. French (Juliet)

    2015-01-01

    textabstractGenome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer

  7. Proteolytic processing of the L-type Ca2+ channel alpha11.2 subunit in neurons [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Olivia R. Buonarati

    2017-07-01

    Full Text Available Background: The L-type Ca2+ channel Cav1.2 is a prominent regulator of neuronal excitability, synaptic plasticity, and gene expression. The central element of Cav1.2 is the pore-forming α11.2 subunit. It exists in two major size forms, whose molecular masses have proven difficult to precisely determine. Recent work suggests that α11.2 is proteolytically cleaved between the second and third of its four pore-forming domains (Michailidis et al,. 2014. Methods: To better determine the apparent molecular masses (MRof the α11.2 size forms, extensive systematic immunoblotting of brain tissue as well as full length and C-terminally truncated α11.2 expressed in HEK293 cells was conducted using six different region–specific antibodies against α11.2. Results: The full length form of α11.2 migrated, as expected, with an apparent MR of ~250 kDa. A shorter form of comparable prevalence with an apparent MR of ~210 kDa could only be detected in immunoblots probed with antibodies recognizing α11.2 at an epitope 400 or more residues upstream of the C-terminus. Conclusions: The main two size forms of α11.2 are the full length form and a shorter form, which lacks ~350 distal C-terminal residues. Midchannel cleavage as suggested by Michailidis et al. (2014 is at best minimal in brain tissue.

  8. The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety.

    Science.gov (United States)

    Scott, Julia A; Goodrich-Hunsaker, Naomi; Kalish, Kristopher; Lee, Aaron; Hunsaker, Michael R; Schumann, Cynthia M; Carmichael, Owen T; Simon, Tony J

    2016-04-01

    Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population. We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety. We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group. Shape alterations are not specific to hippocampal subfields. Alterations in the structure of the anterior hippocampus likely affect function and may impact limbic circuitry. We suggest these alterations potentially contribute to anxiety symptoms in individuals with 22q11.2DS through modulatory pathways. Altered hippocampal morphology may be uniquely linked to anxiety risk factors for schizophrenia, which could be a powerful neuroanatomical marker of schizophrenia risk and hence protection.

  9. Síndrome de deleção 22q11.2: compreendendo o CATCH22

    OpenAIRE

    Rosa,Rafael Fabiano M.; Zen,Paulo Ricardo G.; Roman,Tatiana; Graziadio,Carla; Paskulin,Giorgio Adriano

    2009-01-01

    OBJETIVO:Realizar uma revisão dos aspectos históricos, epidemiológicos, clínicos, etiológicos e laboratoriais da síndrome de deleção 22q11.2, salientando-se a importância e as dificuldades do seu diagnóstico. FONTES DE DADOS: Pesquisa nas bases de dados Medline, Lilacs e SciELO, além da Internet e capítulos de livros em inglês, acerca de publicações feitas entre 1980 e 2008. Para isso, utilizaram-se os descritores "22q11", "DiGeorge", "Velocardiofacial" e "CATCH22". SÍNTESE DOS DADOS: A síndr...

  10. Simulation of SAW Humidity Sensors Based on ( 11 2 ¯ 0 ZnO/R-Sapphire Structures

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    Xiao-Dong Lan

    2016-11-01

    Full Text Available The characteristics of two types of surface acoustic waves SAWs (Rayleigh waves and Love waves propagating in bilayered structures of ( 11 2 ¯ 0 ZnO/R-sapphire are simulated by a finite element method (FEM model, in which both SAWs have crossed propagation directions. Furthermore, based on the bilayered structures, the frequency responses of Rayleigh wave and Love wave humidity sensors are also simulated. Meanwhile, the frequency shifts, insertion loss changes and then the sensitivities of both humidity sensors induced by the adsorbed water layer perturbations, including the mechanical and electrical factors, are calculated numerically. Generally, the characteristics and performances of both sensors are strongly dependent on the thickness of the ZnO films. By appropriate selecting the ratio of the film thickness to SAW wavelength for each kind of the sensors, the performances of both sensors can be optimized.

  11. Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

    Science.gov (United States)

    Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

    2014-08-01

    Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

  12. Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome.

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    Chantal Sellier

    Full Text Available Deletion of the 1.5-3 Mb region of chromosome 22 at locus 11.2 gives rise to the chromosome 22q11.2 deletion syndrome (22q11DS, also known as DiGeorge and Velocardiofacial Syndromes. It is the most common micro-deletion disorder in humans and one of the most common multiple malformation syndromes. The syndrome is characterized by a broad phenotype, whose characterization has expanded considerably within the last decade and includes many associated findings such as craniofacial anomalies (40%, conotruncal defects of the heart (CHD; 70-80%, hypocalcemia (20-60%, and a range of neurocognitive anomalies with high risk of schizophrenia, all with a broad phenotypic variability. These phenotypic features are believed to be the result of a change in the copy number or dosage of the genes located in the deleted region. Despite this relatively clear genetic etiology, very little is known about which genes modulate phenotypic variations in humans or if they are due to combinatorial effects of reduced dosage of multiple genes acting in concert. Here, we report on decreased expression levels of genes within the deletion region of chromosome 22, including DGCR8, in peripheral leukocytes derived from individuals with 22q11DS compared to healthy controls. Furthermore, we found dysregulated miRNA expression in individuals with 22q11DS, including miR-150, miR-194 and miR-185. We postulate this to be related to DGCR8 haploinsufficiency as DGCR8 regulates miRNA biogenesis. Importantly we demonstrate that the level of some miRNAs correlates with brain measures, CHD and thyroid abnormalities, suggesting that the dysregulated miRNAs may contribute to these phenotypes and/or represent relevant blood biomarkers of the disease in individuals with 22q11DS.

  13. Deletion 17p11.2 (Smith-Magenis syndrome) is relatively common among patients having mental retardation and myopia

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    Finucane, B.; Jaeger, E.R. [Elwyn, Inc. PA (United States); Freitag, S.K. [Jefferson Medical College, Philadelphia, PA (United States)

    1994-09-01

    We recently reported the finding of moderate to severe myopia in 6 of 10 patients with Smith-Magenis syndrome (SMS). To investigate the prevalence of SMS among mentally retarded people having myopia, we surveyed a cohort of patients residing at a facility for individuals with mental retardation (MR). Of 547 institutionalized individuals with MR, 72 (13.2%) had moderate to high myopia defined as a visual acuity of minus 3 diopters or more. It should be noted that our institution does not specifically select for people with visual impairment; rather, the facility serves people with a primary diagnosis of MR. Sixty-five of 72 (90.3%) myopic individuals identified were available for cytogenetic analysis. Seventeen (26.2%) of these patients had trisomy 21. Down syndrome (DS) is well known to be associated with eye abnormalities, including myopia. Of 48 individuals with moderate to high myopia not having DS, 5 (10.4%) were shown to have deletions of 17p11.2. This is a high prevalence considering the relative rarity of SMS. By contrast, in a randomized sample of 48 patients without significant myopia at the same facility, we found no individuals with deletion 17p11.2. We conclude that the diagnosis of SMS should be considered in any non-Down syndrome individual having MR and myopia, and that ophthalmologists serving people with MR should be made aware of this deletion syndrome. Furthermore, our results suggest that significant numbers of people having SMS could be identified through selective institutional screening of patients having a combination of MR and moderate to severe myopia.

  14. Dietary intake of total, animal, and vegetable protein and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study.

    Science.gov (United States)

    Sluijs, Ivonne; Beulens, Joline W J; van der A, Daphne L; Spijkerman, Annemieke M W; Grobbee, Diederick E; van der Schouw, Yvonne T

    2010-01-01

    Dietary recommendations are focused mainly on relative dietary fat and carbohydrate content in relation to diabetes risk. Meanwhile, high-protein diets may contribute to disturbance of glucose metabolism, but evidence from prospective studies is scarce. We examined the association among dietary total, vegetable, and animal protein intake and diabetes incidence and whether consuming 5 energy % from protein at the expense of 5 energy % from either carbohydrates or fat was associated with diabetes risk. A prospective cohort study was conducted among 38,094 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Dietary protein intake was measured with a validated food frequency questionnaire. Incident diabetes was verified against medical records. During 10 years of follow-up, 918 incident cases of diabetes were documented. Diabetes risk increased with higher total protein (hazard ratio 2.15 [95% CI 1.77-2.60] highest vs. lowest quartile) and animal protein (2.18 [1.80-2.63]) intake. Adjustment for confounders did not materially change these results. Further adjustment for adiposity measures attenuated the associations. Vegetable protein was not related to diabetes. Consuming 5 energy % from total or animal protein at the expense of 5 energy % from carbohydrates or fat increased diabetes risk. Diets high in animal protein are associated with an increased diabetes risk. Our findings also suggest a similar association for total protein itself instead of only animal sources. Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk. This finding indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful.

  15. The effects of the final stages of the Late Ordovician glaciation on marine palynomorphs (chitinozoans, acritarchs, leiospheres) in well Nl-2 (NE Algerian Sahara).

    Science.gov (United States)

    Paris, F; Bourahrouh, A; Hérissé, A L.

    2000-12-01

    Palynomorph assemblages, especially chitinozoans and acritarchs, from the Upper Ordovician of well Nl-2 (north-east of the Algerian Sahara) are studied in order to precisely date the ultimate effects of the Late Ordovician glaciation and to document the impact of this major climatic stress on the diversity of the palynoplankton. References are made to stable isotope excursions and to global eustatic sea level variations in order to improve the local age determination. The Hassi el Hadjar Formation, i.e. glacio-marine diamictites, is interpreted as a transgressive event resulting from the melting of the northern Gondwana ice cap. It yields poorly preserved and moderately diverse chitinozoans of late Hirnantian age. Acritarchs are more abundant in the lower part of these "microconglomeratic clays", but display a low diversity and are badly preserved throughout the whole formation. Reworked individuals are recorded in both groups. The marine sediments of the M'Kratta Formation of latest Hirnantian age contain better preserved, more abundant and more diverse palynomorph assemblages, especially in the Upper Member. The composition of this palynoplankton indicates a fairly good faunal and phytoplankton recovery after the early Hirnantian climatic stress.The extinction of the Ordovician forms, and the appearance of Silurian type taxa occur only in the uppermost Hirnantian, i.e. following with a slight delay the glacial event. The overlying black shales of Wenlock age (lower part of the Oued Mehaiguène Formation) are indicative of marine anoxic environments. They yield a virtually exclusive, but enormous number of Tasmanacea. The very peculiar composition of this palynoplankton seems to be independent of the Late Ordovician glaciation and is most likely related to the factors that, later, generated and maintained anoxic conditions in this area.A new species of chitinozoan, Spinachitina oulebsiri sp. nov. from the latest Hirnantian M'Kratta Formation, is described and

  16. Reducing our environmental footprint and improving our health: greenhouse gas emission and land use of usual diet and mortality in EPIC-NL: a prospective cohort study.

    Science.gov (United States)

    Biesbroek, Sander; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Verschuren, Wm Monique; van der Schouw, Yvonne T; Kramer, Gerard F H; Tyszler, Marcelo; Temme, Elisabeth H M

    2014-04-07

    Food choices influence health status, but also have a great impact on the environment. The production of animal-derived foods has a high environmental burden, whereas the burden of refined carbohydrates, vegetables and fruit is low. The aim of this study was to investigate the associations of greenhouse gas emission (GHGE) and land use of usual diet with mortality risk, and to estimate the effect of a modelled meat substitution scenario on health and the environment. The usual diet of 40011 subjects in the EPIC-NL cohort was assessed using a food frequency questionnaire. GHGE and land use of food products were based on life cycle analysis. Cox proportional hazard ratios (HR) were calculated to determine relative mortality risk. In the modelled meat-substitution scenario, one-third (35 gram) of the usual daily meat intake (105 gram) was substituted by other foods. During a follow-up of 15.9 years, 2563 deaths were registered. GHGE and land use of the usual diet were not associated with all-cause or with cause-specific mortality. Highest vs. lowest quartile of GHGE and land use adjusted hazard ratios for all-cause mortality were respectively 1.00 (95% CI: 0.86-1.17) and 1.05 (95% CI: 0.89-1.23). Modelled substitution of 35 g/d of meat with vegetables, fruit-nuts-seeds, pasta-rice-couscous, or fish significantly increased survival rates (6-19%), reduced GHGE (4-11%), and land use (10-12%). There were no significant associations observed between dietary-derived GHGE and land use and mortality in this Dutch cohort. However, the scenario-study showed that substitution of meat with other major food groups was associated with a lower mortality risk and a reduced environmental burden. Especially when vegetables, fruit-nuts-seeds, fish, or pasta-rice-couscous replaced meat.

  17. Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India

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    Chaudhary Isha

    2010-06-01

    Full Text Available Abstract Background The 22q11.2 microdeletion syndrome is a common condition that is associated with cardiac as well as extra-cardiac manifestations. Its prevalence and manifestations from north India has not been reported. This study was designed to determine the prevalence and ability of clinical criteria to predict 22q11.2 microdeletion. Methods A total of 146 cases of cardiac malformation requiring tertiary care at a teaching hospital were prospectively screened for 22q11.2 microdeletion using fluorescence in situ hybridization test. Detailed clinical information was obtained as per guidelines of Tobias, et al (1999. Results Nine out of 146 patients (6.16% was found to have 22q11.2 microdeletion. All the positive patients showed the presence of extra-cardiac features of 22q11.2 microdeletion syndrome. None of the cases with isolated cardiac defect were positive for microdeletion. Conclusions It seems that 22q11.2 microdeletion syndrome is over-suspected in children with isolated congenital heart defects. Screening for 22q11.2 microdeletion should be considered in those cardiac malformation cases which have extra-cardiac manifestations in the form of facial dysmorphism and hypocalcaemia.

  18. Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India.

    Science.gov (United States)

    Halder, Ashutosh; Jain, Manish; Chaudhary, Isha; Kabra, Madhulika

    2010-06-23

    The 22q11.2 microdeletion syndrome is a common condition that is associated with cardiac as well as extra-cardiac manifestations. Its prevalence and manifestations from north India has not been reported. This study was designed to determine the prevalence and ability of clinical criteria to predict 22q11.2 microdeletion. A total of 146 cases of cardiac malformation requiring tertiary care at a teaching hospital were prospectively screened for 22q11.2 microdeletion using fluorescence in situ hybridization test. Detailed clinical information was obtained as per guidelines of Tobias, et al (1999). Nine out of 146 patients (6.16%) was found to have 22q11.2 microdeletion. All the positive patients showed the presence of extra-cardiac features of 22q11.2 microdeletion syndrome. None of the cases with isolated cardiac defect were positive for microdeletion. It seems that 22q11.2 microdeletion syndrome is over-suspected in children with isolated congenital heart defects. Screening for 22q11.2 microdeletion should be considered in those cardiac malformation cases which have extra-cardiac manifestations in the form of facial dysmorphism and hypocalcaemia.

  19. R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice.

    Science.gov (United States)

    Stoppel, Laura J; Kazdoba, Tatiana M; Schaffler, Melanie D; Preza, Anthony R; Heynen, Arnold; Crawley, Jacqueline N; Bear, Mark F

    2018-02-01

    Human chromosome 16p11.2 microdeletion is among the most common gene copy number variations (CNVs) known to confer risk for intellectual disability (ID) and autism spectrum disorder (ASD) and affects an estimated 3 in 10 000 people. Caused by a single copy deletion of ~27 genes, 16p11.2 microdeletion syndrome is characterized by ID, impaired language, communication and socialization skills, and ASD. Studies in animal models where a single copy of the syntenic 16p11.2 region has been deleted have revealed morphological, behavioral, and electrophysiological abnormalities. Previous studies suggested the possibility of some overlap in the mechanisms of pathophysiology in 16p11.2 microdeletion syndrome and fragile X syndrome. Improvements in fragile X phenotypes have been observed following chronic treatment with R-baclofen, a selective agonist of GABA B receptors. We were therefore motivated to investigate the effects of chronic oral R-baclofen administration in two independently generated mouse models of 16p11.2 microdeletion syndrome. In studies performed across two independent laboratories, we found that chronic activation of GABA B receptors improved performance on a series of cognitive and social tasks known to be impaired in two different 16p11.2 deletion mouse models. Our findings suggest that R-baclofen may have clinical utility for some of the core symptoms of human 16p11.2 microdeletion syndrome.

  20. A cross-sectional analysis of the development of response inhibition in children with Chromosome 22q11.2 Deletion Syndrome

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    Heather M Shapiro

    2013-08-01

    Full Text Available Chromosome 22q11.2 Deletion Syndrome (22q11.2DS is a neurogenetic disorder that is associated with cognitive impairments and significantly elevated risk for developing schizophrenia. While impairments in response inhibition are central to executive dysfunction in schizophrenia, the nature and development of such impairments in children with 22q11.2DS, a group at high risk for the disorder, are not clear. Here we used a classic Go/No-Go paradigm to quantify proactive (anticipatory stopping and reactive (actual stopping response inhibition in 47 children with 22q11.2DS and 36 typically developing (TD children, all ages 7-14. A cross-sectional design was used to examine age-related associations with response inhibition. When compared with TD individuals, children with 22q11.2DS demonstrated typical proactive response inhibition at all ages. By contrast, reactive response inhibition was impaired in children with 22q11.2DS relative to TD children. While older age predicted better reactive response inhibition in TD children, there was no age-related association with reactive response inhibition in children with 22q11.2DS. Closer examination of individual performance data revealed a wide range of performance abilities in older children with 22q11.2DS; some typical and others highly impaired. The results of this cross-sectional analysis suggest an impaired developmental trajectory of reactive response inhibition in some children with 22q11.2DS that might be related to atypical development of neuroanatomical systems underlying this cognitive process. As part of a larger study, this investigation might help identify risk factors for conversion to schizophrenia and lead to early diagnosis and preventive intervention.

  1. Partial microduplication in the histone acetyltransferase complex member KANSL1 is associated with congenital heart defects in 22q11.2 microdeletion syndrome patients.

    Science.gov (United States)

    León, Luis E; Benavides, Felipe; Espinoza, Karena; Vial, Cecilia; Alvarez, Patricia; Palomares, Mirta; Lay-Son, Guillermo; Miranda, Macarena; Repetto, Gabriela M

    2017-05-11

    22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion disorder in humans, with an incidence of 1/4000 live births. It is caused by a heterozygous deletion of 1.5-3 Mb on chromosome region 22q11.2. Patients with the deletion present features that include neuropsychiatric problems, craniofacial abnormalities and cardiovascular malformations. However, the phenotype is highly variable and the factors related to the clinical heterogeneity are not fully understood. About 65% of patients with 22q11.2DS have congenital heart defects (CHD). The main goal of this study was to identify common CNVs in 22q11.2DS patients that could be associated with the incomplete penetrance of CHD. Analysis of genomic DNA from 253 patients with 22q11.2DS using array technology showed an association between a microduplication located in region 17q21.31 and CHD (p-value = 0.023, OR = 2.75, 95% CI = 1.17-7.03). This region includes the first three exons of KANSL1 gene. Bioinformatic analysis showed that KANSL1 and CRKL, a gene in the commonly deleted region of 22q11.2DS, are part of the same regulatory module in a miRNA-mRNA network. These results show that a KANSL1 microduplication, in combination with the 22q11.2 deletion, is associated with increased risk of CHD in these patients, suggesting that KANSL1 plays a role as a modifier gene in 22q11.2DS patients.

  2. Dysregulation of TBX1 dosage in the anterior heart field results in congenital heart disease resembling the 22q11.2 duplication syndrome.

    Science.gov (United States)

    Hasten, Erica; McDonald-McGinn, Donna M; Crowley, Terrence B; Zackai, Elaine; Emanuel, Beverly S; Morrow, Bernice E; Racedo, Silvia E

    2018-03-02

    Non-allelic homologous recombination events on chromosome 22q11.2 during meiosis can result in either the deletion (22q11.2DS) or duplication (22q11.2DupS) syndrome. Although the spectrum and frequency of congenital heart disease (CHD) are known for 22q11.2DS, there is less known for 22q11.2DupS. We now evaluated cardiac phenotypes in 235 subjects with 22q11.2DupS including 102 subjects we collected and 133 subjects that were previously reported as a confirmation and found 25% have CHD, mostly affecting the cardiac outflow tract (OFT). Previous studies have shown that global loss or gain of function (LOF; GOF) of mouse Tbx1, encoding a T-box transcription factor mapping to the region of synteny to 22q11.2, results in similar OFT defects. To further evaluate Tbx1 function in the progenitor cells forming the cardiac OFT, termed the anterior heart field, Tbx1 was overexpressed using the Mef2c-AHF-Cre driver (Tbx1 GOF). Here we found that all resulting conditional GOF embryos had a persistent truncus arteriosus (PTA), similar to what was previously reported for conditional Tbx1 LOF mutant embryos. To understand the basis for the PTA in the conditional GOF embryos, we found that proliferation in the Mef2c-AHF-Cre lineage cells before migrating to the heart, was reduced and critical genes were oppositely changed in this tissue in Tbx1 GOF embryos versus conditional LOF embryos. These results suggest that a major function of TBX1 in the AHF is to maintain the normal balance of expression of key cardiac developmental genes required to form the aorta and pulmonary trunk, which is disrupted in 22q11.2DS and 22q11.2DupS.

  3. Chromosome 22q11.2 microdeletion in children with conotruncal heart defects: frequency, associated cardiovascular anomalies, and outcome following cardiac surgery.

    Science.gov (United States)

    Ziolkowska, Lidia; Kawalec, Wanda; Turska-Kmiec, Anna; Krajewska-Walasek, Malgorzata; Brzezinska-Rajszys, Grazyna; Daszkowska, Jadwiga; Maruszewski, Bogdan; Burczynski, Piotr

    2008-10-01

    The association of conotruncal heart defects with 22q11.2 chromosomal microdeletions is well established. However, it is not clear whether particular types of conotruncal malformations or additional cardiovascular anomalies are associated with microdeletions. In addition, cardiac surgery outcome in children with conotruncal defects and del22q11.2 is not well described. We prospectively enrolled 214 children with conotruncal defects: 126 with tetralogy of Fallot (TOF), 18 with pulmonary atresia-ventricular septal defect (PA-VSD), 15 with truncus arteriosus communis (TAC) type I, one with interrupted aortic arch (IAA) type B, and 54 with the transposition of great arteries, who were consecutively hospitalized at the Pediatric Cardiology Department between 2003 and 2005. 22q11.2 microdeletion was identified by fluorescence in situ hybridization. The postoperative course following cardiac surgery was compared in patients with TOF and its more severe form, PA-VSD, with/without del22q11.2 (groups A and B) and TAC with/without del22q11.2 (groups C and D). In 15 of 214 patients, 22q11.2 microdeletion was diagnosed (in 11 with TOF/PA-VSD, in three with TAC, in one with IAA type B). In patients with TOF/PA-VSD and microdeletion anatomic features that were significantly associated with 22q11.2, deletion included right aortic arch (p = 0.018), aberrant right subclavian artery (p microdeletion. We conclude that additional cardiovascular anomalies are significantly more frequent in children with 22q11.2 microdeletion and TOF/PA-VSD. Children with conotruncal heart defects and 22q11.2 microdeletion more frequently experienced complicated postoperative course after cardiac surgery.

  4. Diagnosing Smith-Magenis syndrome and duplication 17p11.2 syndrome by RAI1 gene copy number variation using quantitative real-time PCR.

    Science.gov (United States)

    Truong, Hoa T; Solaymani-Kohal, Sara; Baker, Kevin R; Girirajan, Santhosh; Williams, Stephen R; Vlangos, Christopher N; Smith, Ann C M; Bunyan, David J; Roffey, Paul E; Blanchard, Christopher L; Elsea, Sarah H

    2008-03-01

    Smith-Magenis syndrome (SMS) and duplication 17p11.2 (dup17p11.2) syndrome are multiple congenital anomalies/mental retardation disorders resulting from either a deletion or duplication of the 17p11.2 region, respectively. The retinoic acid induced 1 (RAI1) gene is the causative gene for SMS and is included in the 17p11.2 region of dup17p11.2 syndrome. Currently SMS and dup17p11.2 syndrome are diagnosed using a combination of clinically recognized phenotypes and molecular cytogenetic analyses such as fluorescent in situ hybridization (FISH). However, these methods have proven to be highly expensive, time consuming, and dependent upon the low resolving capabilities of the assay. To address the need for improved diagnostic methods for SMS and dup17p11.2 syndrome, we designed a quantitative real-time PCR (Q-PCR) assay that measures RAI1 copy number using the comparative C(t) method, DeltaDeltaC(t). We tested our assay with samples blinded to their previous SMS or dup17p11.2 syndrome status. In all cases, we were able to determine RAI1 copy number status and render a correct diagnosis accordingly. We validated these results by both FISH and multiplex ligation-dependent probe amplification (MLPA). We conclude that Q-PCR is an accurate, reproducible, low-cost, and reliable assay that can be employed for routine use in SMS and dup17p11.2 diagnosis.

  5. Mitochondria in complex psychiatric disorders: Lessons from mouse models of 22q11.2 deletion syndrome: Hemizygous deletion of several mitochondrial genes in the 22q11.2 genomic region can lead to symptoms associated with neuropsychiatric disease.

    Science.gov (United States)

    Devaraju, Prakash; Zakharenko, Stanislav S

    2017-02-01

    Mitochondrial ATP synthesis, calcium buffering, and trafficking affect neuronal function and survival. Several genes implicated in mitochondrial functions map within the genomic region associated with 22q11.2 deletion syndrome (22q11DS), which is a key genetic cause of neuropsychiatric diseases. Although neuropsychiatric diseases impose a serious health and economic burden, their etiology and pathogenesis remain largely unknown because of the dearth of valid animal models and the challenges in investigating the pathophysiology in neuronal circuits. Mouse models of 22q11DS are becoming valid tools for studying human psychiatric diseases, because they have hemizygous deletions of the genes that are deleted in patients and exhibit neuronal and behavioral abnormalities consistent with neuropsychiatric disease. The deletion of some 22q11DS genes implicated in mitochondrial function leads to abnormal neuronal and synaptic function. Herein, we summarize recent findings on mitochondrial dysfunction in 22q11DS and extend those findings to the larger context of schizophrenia and other neuropsychiatric diseases. © 2017 WILEY Periodicals, Inc.

  6. Fluorescence in situ hybridization (FISH screening for the 22q11.2 deletion in patients with clinical features of velocardiofacial syndrome but without cardiac anomalies

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    Paula Sandrin-Garcia

    2007-01-01

    Full Text Available The velocardiofacial syndrome (VCFS, a condition associated with 22q11.2 deletions, is characterized by a typical facies, palatal anomalies, learning disabilities, behavioral disturbances and cardiac defects. We investigated the frequency of these chromosomal deletions in 16 individuals with VCFS features who presented no cardiac anomalies, one of the main characteristics of VCFS. Fluorescent in situ hybridization (FISH with the N25 (D22S75; 22q11.2 probe revealed deletions in ten individuals (62%. Therefore, even in the absence of cardiac anomalies testing for the 22q11.2 microdeletions in individuals showing other clinical features of this syndrome is recommended.

  7. Prospective Control Abilities during Visuo-Manual Tracking in Children with 22q11.2 Deletion Syndrome Compared to Age- and IQ-Matched Controls

    Science.gov (United States)

    Van Aken, Katrijn; Swillen, Ann; Beirinckx, Marc; Janssens, Luc; Caeyenberghs, Karen; Smits-Engelsman, Bouwien

    2010-01-01

    To examine whether children with a 22q11.2 Deletion syndrome (22q11.2DS) are able to use prospective control, 21 children with 22q11.2DS (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.05 [plus or minus] 10.2) and 21 control children (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.38 [plus or minus] 12.0) were asked to perform a visuo-manual…

  8. Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India

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    Halder, Ashutosh; Jain, Manish; Chaudhary, Isha; Kabra, Madhulika

    2010-01-01

    Abstract Background The 22q11.2 microdeletion syndrome is a common condition that is associated with cardiac as well as extra-cardiac manifestations. Its prevalence and manifestations from north India has not been reported. This study was designed to determine the prevalence and ability of clinical criteria to predict 22q11.2 microdeletion. Methods A total of 146 cases of cardiac malformation requiring tertiary care at a teaching hospital were prospectively screened for 22q11.2 microdeletion ...

  9. Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Vorstman, Jacob A S; Breetvelt, Elemi J; Duijff, Sasja N; Eliez, Stephan; Schneider, Maude; Jalbrzikowski, Maria; Armando, Marco; Vicari, Stefano; Shashi, Vandana; Hooper, Stephen R; Chow, Eva W C; Fung, Wai Lun Alan; Butcher, Nancy J; Young, Donald A; McDonald-McGinn, Donna M; Vogels, Annick; van Amelsvoort, Therese; Gothelf, Doron; Weinberger, Ronnie; Weizman, Abraham; Klaassen, Petra W J; Koops, Sanne; Kates, Wendy R; Antshel, Kevin M; Simon, Tony J; Ousley, Opal Y; Swillen, Ann; Gur, Raquel E; Bearden, Carrie E; Kahn, René S; Bassett, Anne S

    2015-04-01

    Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age. To determine whether early cognitive decline is associated with risk of psychotic disorder in 22q11DS. Prospective longitudinal cohort study. As part of an international research consortium initiative, we used the largest data set of intelligence (IQ) measurements in patients with 22q11DS reported to date to investigate longitudinal IQ trajectories and the risk of subsequent psychotic illness. A total of 829 patients with a confirmed hemizygous 22q11.2 deletion, recruited through 12 international clinical research sites, were included. Both psychiatric assessments and longitudinal IQ measurements were available for a subset of 411 patients (388 with ≥1 assessment at age 8-24 years). Diagnosis of a psychotic disorder, initial IQ, longitudinal IQ trajectory, and timing of the last psychiatric assessment with respect to the last IQ test. Among 411 patients with 22q11DS, 55 (13.4%) were diagnosed as having a psychotic disorder. The mean (SD) age at the most recent psychiatric assessment was 16.1 (6.2) years. The mean (SD) full-scale IQ at first cognitive assessment was lower in patients who developed a psychotic disorder (65.5 [12.0]) compared with those without a psychotic disorder (74.0 [14.0]). On average, children with 22q11DS showed a mild decline in IQ (full-scale IQ, 7.04 points) with increasing age, particularly in the domain of verbal IQ (9.02 points). In those who developed psychotic illness, this decline was significantly steeper (P < .001). Those with a negative deviation from the average cognitive trajectory observed in 22q11DS were at significantly increased risk for the development of a psychotic disorder (odds ratio = 2.49; 95% CI, 1.24-5.00; P = .01). The divergence of verbal IQ

  10. Distinct karyotypes in two offspring of a man with jumping translocation karyotype 45,XY,der(16)t(16;22)(q24;q11.2), -22 [59]/45,XY,der(1)t(1;22)(p36;q11.2), -22 [11]/45,XY,der(22)t(22;22)(p13;q11.2), -22 [10].

    Science.gov (United States)

    Hu, Hua; Yao, Hong; Dong, Yanlin; Long, Yang; Xu, Liang; Hu, Bing; Xu, Gang; Liang, Zhiqing

    2014-08-01

    We examined a man and his daughter, who both had different jumping translocation karyotypes. The man's wife was pregnant and had been referred for prenatal diagnosis of the fetus. The karyotype of the husband's peripheral blood lymphocytes was 45,XY,der(16)t(16;22)(q24;q11.2), -22 [59]/45,XY,der(1)t(1;22)(p36;q11.2), -22 [11]/45,XY,der(22)t(22;22)(p13;q11.2), -22 [10]. The karyotype of the daughter's peripheral blood lymphocytes was 45,XX,der(16)t(16;22)(q24;q11.2), -22 [45]/45,XX,der(9)t(9;22)(q34;q11.2), -22 [30]/45,XX,der(5)t(5;22)(q35;q11.2), -22 [25]. The wife and the fetus both had a normal karyotype. To the best of our knowledge, the present familial transmitted jumping translocation has not been previously described and the jumping translocation in the husband and daughter did not cause any phenotypic abnormalities. © 2014 Wiley Periodicals, Inc.

  11. Comparing the neural bases of self-referential processing in typically developing and 22q11.2 adolescents.

    Science.gov (United States)

    Schneider, Maude; Debbané, Martin; Lagioia, Annalaura; Salomon, Roy; d'Argembeau, Arnaud; Eliez, Stephan

    2012-04-01

    The investigation of self-reflective processing during adolescence is relevant, as this period is characterized by deep reorganization of the self-concept. It may be the case that an atypical development of brain regions underlying self-reflective processing increases the risk for psychological disorders and impaired social functioning. In this study, we investigated the neural bases of self- and other-related processing in typically developing adolescents and youths with 22q11.2 deletion syndrome (22q11DS), a rare neurogenetic condition associated with difficulties in social interactions and increased risk for schizophrenia. The fMRI paradigm consisted in judging if a series of adjectives applied to the participant himself/herself (self), to his/her best friend or to a fictional character (Harry Potter). In control adolescents, we observed that self- and other-related processing elicited strong activation in cortical midline structures (CMS) when contrasted with a semantic baseline condition. 22q11DS exhibited hypoactivation in the CMS and the striatum during the processing of self-related information when compared to the control group. Finally, the hypoactivation in the anterior cingulate cortex was associated with the severity of prodromal positive symptoms of schizophrenia. The findings are discussed in a developmental framework and in light of their implication for the development of schizophrenia in this at-risk population. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Performance analysis of a 11.2 kWp roof top grid-connected PV system in Eastern India

    Directory of Open Access Journals (Sweden)

    Renu Sharma

    2017-11-01

    Full Text Available Barren land and roof tops of buildings are being increasingly used worldwide to install solar panels for generating electricity. One such step has been taken by Siksha ‘O’Anusandhan University, Bhubaneswar (Latitude 20.24° N and Longitude 80.85° E by installing a 11.2 kWp grid connected solar power system during February, 2014. This PV system is tilted at an angle of 21° on the top floor of a 25 metre height building. This system was installed This paper presents the results of this grid connected photovoltaic system which was monitored between September 2014 to August 2015. The entire electricity generated by the system was fed into the state grid. The different parameters of the system studied include PV module efficiency, array yield, final yield, inverter efficiency and performance ratio of the system. The total energy generated during this period was found to be 14.960 MWh and the PV module efficiency, inverter efficiency and performance ratio were found to be 13.42%, 89.83% and 0.78 respectively.

  13. Source monitoring for actions in adolescents with 22q11.2 deletion syndrome (22q11DS).

    Science.gov (United States)

    Debbané, M; Van der Linden, M; Glaser, B; Eliez, S

    2008-06-01

    Source monitoring consists in identifying the origin of mental events. Recent research suggests that confusions over internally generated mental events may represent a cognitive marker for increased proneness to psychotic symptoms and disorders. We have examined source monitoring for actions in adolescents with the 22q11.2 deletion syndrome (22q11DS), a neurogenetic disease associated with high rates of schizophrenia during adulthood, and expected to observe source monitoring deficits in comparison to IQ-matched and typically developing controls. Eighteen adolescents with 22q11DS, 17 adolescents matched for age and IQ, and also 17 adolescents matched for age participated in this study. Our adapted action monitoring paradigm asked subjects to visualize a series of actions in three different conditions: (1) visualize themselves performing the action; (2) visualize the experimenter performing the action; or (3) simply repeat the action statements without visualization of the action performer. The adolescents with 22q11DS performed adequately in terms of recognition (hits), but in comparison to both control groups, they committed more source confusions on correctly recognized items. Further examination revealed that the adolescents were more likely to demonstrate confusions between exterior sources in which the self was not involved. Source monitoring deficits can be observed in adolescents with 22q11DS, a syndrome putting them at high risk for developing schizophrenia. These deficits are discussed in terms of early cognitive processes associated with genetic risk for schizophrenia.

  14. Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility.

    Science.gov (United States)

    Nuttle, Xander; Giannuzzi, Giuliana; Duyzend, Michael H; Schraiber, Joshua G; Narvaiza, Iñigo; Sudmant, Peter H; Penn, Osnat; Chiatante, Giorgia; Malig, Maika; Huddleston, John; Benner, Chris; Camponeschi, Francesca; Ciofi-Baffoni, Simone; Stessman, Holly A F; Marchetto, Maria C N; Denman, Laura; Harshman, Lana; Baker, Carl; Raja, Archana; Penewit, Kelsi; Janke, Nicolette; Tang, W Joyce; Ventura, Mario; Banci, Lucia; Antonacci, Francesca; Akey, Joshua M; Amemiya, Chris T; Gage, Fred H; Reymond, Alexandre; Eichler, Evan E

    2016-08-11

    Genetic differences that specify unique aspects of human evolution have typically been identified by comparative analyses between the genomes of humans and closely related primates, including more recently the genomes of archaic hominins. Not all regions of the genome, however, are equally amenable to such study. Recurrent copy number variation (CNV) at chromosome 16p11.2 accounts for approximately 1% of cases of autism and is mediated by a complex set of segmental duplications, many of which arose recently during human evolution. Here we reconstruct the evolutionary history of the locus and identify bolA family member 2 (BOLA2) as a gene duplicated exclusively in Homo sapiens. We estimate that a 95-kilobase-pair segment containing BOLA2 duplicated across the critical region approximately 282 thousand years ago (ka), one of the latest among a series of genomic changes that dramatically restructured the locus during hominid evolution. All humans examined carried one or more copies of the duplication, which nearly fixed early in the human lineage--a pattern unlikely to have arisen so rapidly in the absence of selection (P sapiens-specific duplication. In summary, the duplicative transposition of BOLA2 at the root of the H. sapiens lineage about 282 ka simultaneously increased copy number of a gene associated with iron homeostasis and predisposed our species to recurrent rearrangements associated with disease.

  15. Submicroscopic deletions at 22q11.2: Variability of the clinical picture and delineation of a commonly deleted region

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Shaffer, L.G.; Greenberg, F. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1995-03-27

    DiGeorge anomaly (DGA) and velo-cardio-facial syndrome (VCFS) are frequently associated with monosomy of chromosome region 22q11. Most patients have a submicroscopic deletion, recently estimated to be at least 1-2 Mb. It is not clear whether individuals who present with only some of the features of these conditions have the deletion, and if so, whether the size of the deletion varies from those with more classic phenotypes. We have used fluorescence in situ hybridization (FISH) to assess the deletion status of 85 individuals referred to us for molecular analysis, with a wide range of DGA-like or VCFS-like clinical features. The test probe used was the cosmid sc11.1, which detects two loci about 2 Mb apart in 22q11.2. Twenty-four patients carried the deletion. Of the deleted patients, most had classic DGA or VCFS phenotypes, but 6 deleted patients had mild phenotypes, including 2 with minor facial anomalies and velopharyngeal incompetence as the only presenting signs. Despite the great phenotypic variability among the deleted patients, none had a deletion smaller than the 2-Mb region defined by sc11.1. Smaller deletions were not detected in patients with particularly suggestive phenotypes who were not deleted for sc11.1, even when tested with two other probes from the DGA/VCFS region. 24 refs., 2 figs., 2 tabs.

  16. Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders

    Science.gov (United States)

    Hiroi, N; Takahashi, T; Hishimoto, A; Izumi, T; Boku, S; Hiramoto, T

    2013-01-01

    Recently discovered genome-wide rare copy number variants (CNVs) have unprecedented levels of statistical association with many developmental neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder. However, as CNVs often include multiple genes, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Mouse models of CNVs are in use to delve into the precise mechanisms through which CNVs contribute to disorders and associated traits. Based on human and mouse model studies on rare CNVs within human chromosome 22q11.2, we propose that alterations of a distinct set of multiple, noncontiguous genes encoded in this chromosomal region, in concert with modulatory impacts of genetic background and environmental factors, variably shift the probabilities of phenotypes along a predetermined developmental trajectory. This model can be further extended to the study of other CNVs and may serve as a guide to help characterize the impact of genes in developmental neuropsychiatric disorders. PMID:23917946

  17. Hypoventilation in REM sleep in a case of 17p11.2 deletion (Smith-Magenis syndrome).

    Science.gov (United States)

    Leoni, Chiara; Cesarini, Laura; Dittoni, Serena; Battaglia, Domenica; Novelli, Antonio; Bernardini, Laura; Losurdo, Anna; Vollono, Catello; Testani, Elisa; Della Marca, Giacomo; Zampino, Giuseppe

    2010-03-01

    We describe a 2-year-old baby affected by Smith-Magenis syndrome (SMS), due to 17p11.2 deletion, who presented repeated episodes of hemoglobin desaturation during REM sleep. The boy, aged 14 months, presented a phenotype characterized by psychomotor delay, right posterior plagiocephaly, telecanthus, strabismus, upslanting palpebral fissures, broad hypoplastic nasal bridge, short philtrum, deep ring shaped skin creases around the limbs, proximal syndactyly, bilateral hypoacusia. Polysomnographic (PSG) recording showed episodes of REM-related hypoventilation (hemoglobin desaturations without apneas or hypopneas). Sleep disorders are present in almost all the cases of SMS, but very few reports describe the sleep-related respiratory patterns. The finding of REM hypoventilation in SMS does not allow an unequivocal interpretation. It could reflect a subclinical restrictive respiratory impairment or, alternatively, an impairment of central respiratory control during REM sleep. In SMS children, respiratory abnormalities during sleep, and in particular during REM sleep, may cause sleep disruption, reduction of time spent in REM sleep, and daytime sleepiness. We therefore suggest that some sleep abnormalities described in SMS could be consequent to Sleep Disordered Breathing, and in particular to REM hypoventilation. Sleep studies in SMS should include the recording of respiratory parameters. (c) 2010 Wiley-Liss, Inc.

  18. Along the N=126 closed shell: study of $^{205}$Au through its $\\pi h_{11/2}^{-1}$ isomeric decay

    CERN Multimedia

    2002-01-01

    Excited states have been identified in only three of the N=126 closed shell nuclei 'below' $^{208}$Pb, $^{207}$Tl, $^{206}$Hg and very recently $^{204}$Pt. We aim to extend our knowledge of the neutron-rich N=126 nuclei by observing the internal decay of the $\\pi h^{-1}_{11/2}$ excited state in $^{205}$Au, which is expected to be isomeric. In addition, the decay of the analogous states in the N=122 and N=124 $^{201,203}$Au will be studied. The lifetimes of the expected isomeric states are crucial for the success of the experiment, and they are estimated to be in the range of 0.3-20 s. These are long enough to enable the extraction from the source, but shorter than the $\\beta$-decay half-lives. Proton single-particle energies and transition rates will be extracted, providing information about the robustness of the N=126 shell-closure. Three days of beam-time is requested.

  19. Context-based FISH localization of genomic rearrangements within chromosome 15q11.2q13 duplicons

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    Knoll Joan HM

    2011-08-01

    Full Text Available Abstract Background Segmental duplicons (SDs predispose to an increased frequency of chromosomal rearrangements. These rearrangements can cause a diverse range of phenotypes due to haploinsufficiency, in cis positional effects or gene interruption. Genomic microarray analysis has revealed gene dosage changes adjacent to duplicons, but the high degree of similarity between duplicon sequences has confounded unequivocal assignment of chromosome breakpoints within these intervals. In this study, we localize rearrangements within duplicon-enriched regions of Angelman/Prader-Willi (AS/PWS syndrome chromosomal deletions with fluorescence in situ hybridization (FISH. Results Breakage intervals in AS deletions were localized recursively with short, coordinate-defined, single copy (SC and low copy (LC genomic FISH probes. These probes were initially coincident with duplicons and regions of previously reported breakage in AS/PWS. Subsequently, probes developed from adjacent genomic intervals more precisely delineated deletion breakage intervals involving genes, pseudogenes and duplicons in 15q11.2q13. The observed variability in the deletion boundaries within previously described Class I and Class II deletion AS samples is related to the local genomic architecture in this chromosomal region. Conclusions Chromosome 15 abnormalities associated with SDs were precisely delineated at a resolution equivalent to genomic Southern analysis. This context-dependent approach can define the boundaries of chromosome rearrangements for other genomic disorders associated with SDs.

  20. Prenatal diagnosis of 22q11.2 deletion syndrome associated with right aortic arch, left ductus arteriosus, cardiomegaly, and pericardial effusion

    Directory of Open Access Journals (Sweden)

    Yen-Ni Chen

    2016-02-01

    Conclusion: Chromosome abnormalities have been found in patients with RAA. Prenatal diagnosis of RAA with or without intracardiac or extracardiac anomalies should include a diagnosis of 22q11.2 deletion syndrome.

  1. Interstitial deletion 11(p11.12p11.2) and analphoid marker formation results in inherited Potocki-Shaffer syndrome.

    Science.gov (United States)

    Chuang, Louise; Wakui, Keiko; Sue, Whey-Chen; Su, Mei-Hsu; Shaffer, Lisa G; Kuo, Pao-Lin

    2005-03-01

    We report a family with inherited Potocki-Shaffer syndrome. The phenotypically normal mother has an interstitial deletion of 11(p11.12p11.2) with neocentric marker chromosome formation. The marker chromosome contains the deleted material on 11p11.2 and is likely a ring. The patient inherited a maternal deleted chromosome 11 but not the marker chromosome, thus resulting in an unbalanced karyotype along with the phenotype of Potocki-Shaffer syndrome. The deleted region in our case-11p11.12p11.2-is a newly reported site of constitutional neocentromere formation. This is also the first report describing deletion of 11p11.12-p11.2 and neocentromere formation resulting in inherited Potocki-Shaffer syndrome. (c) 2005 Wiley-Liss, Inc.

  2. Brain and Behavior in Children with 22Q11.2 Deletion Syndrome: A Volumetric and Voxel-Based Morphometry MRI Study

    Science.gov (United States)

    Campbell, Linda E.; Daly, Eileen; Toal, Fiona; Stevens, Angela; Azuma, Rayna; Catani, Marco; Ng, Virginia; Van Amelsvoort, Therese; Chitnis, Xavier; Cutter, William; Murphy, Declan G. M.; Murphy, Kieran C.

    2006-01-01

    In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit hyperactivity disorder…

  3. Microdeletion and microduplication 22q11.2 screening in 295 patients with clinical features of DiGeorge/Velocardiofacial syndrome.

    Science.gov (United States)

    Brunet, Anna; Gabau, Elisabeth; Perich, Rosa Maria; Valdesoiro, Laura; Brun, Carme; Caballín, Maria Rosa; Guitart, Miriam

    2006-11-15

    The 22q11.2 region is susceptible to chromosomal rearrangements, leading to various types of congenital malformation and mental retardation. The most common anomaly is 22q11.2 microdeletion, associated with DiGeorge/Velocardiofacial syndrome (DG/VCFS). Recently the microduplication 22q11.2 syndrome has been identified. Some clinical features in patients with this new chromosomal disorder present a substantial overlap with DG/VCFS. The aim of this hospital-based study was to evaluate the incidence of deletions and duplications on 22q11.2 in patients with DG/VCFS features. We investigated a group of 295 patients with widely variable manifestations associated with DG/VCFS. Along with the clinical diagnoses different anomalies were noted such as conotruncal cardiac anomaly, velopharyngeal insufficiency, characteristic facial dysmorphic features, language impairment, developmental delay/learning difficulties, and immunologic anomalies or thymic hypoplasia. Laboratory studies included conventional cytogenetic and FISH testing. Metaphase and interphase cells were analyzed for the presence of 22q11.2 microdeletion or microduplication. There were 12 patients who carried 22q11.2 microdeletion and no microduplication in the region was identified. Other chromosomal anomalies were reported in five patients with an overlapped DG/VCFS phenotype. All patients with 22q11.2 microdeletion showed a characteristic phenotype of DG/VCFS. We did not identify 22q11.2 microduplication, suggesting that this is a rare event in patients with DG/VCFS features. (c) 2006 Wiley-Liss, Inc.

  4. Co-existence of other copy number variations with 22q11.2 deletion or duplication: a modifier for variable phenotypes of the syndrome?

    Directory of Open Access Journals (Sweden)

    Li Deling

    2012-04-01

    Full Text Available Abstract Background The phenotype in patients with a 22q11.2 deletion or duplication can be extremely variable, and the causes of such as variations are not well known. Results We observed additional copy number variations (CNVs in 2 of 15 cases with a 22q11.2 deletion or duplication. Both cases were newborn babies referred for severe congenital heart defects. The first case had a deletion with a size of approximately 1.56 Mb involving multiple genes including STS in the Xp22.31 region along with a 22q11.2 deletion. The second case had a duplication of 605 kb in the 15q13.3 region encompassing CHRNA7 and a deletion of 209 kb involving the RBFOX1 gene in the 16p13.2 region, in addition to 22q11.2 duplication. Discussion Our observations have shown that additional CNVs are not rare (2/15, 13% in patients with a 22q11.2 deletion or duplication. We speculate that these CNVs may contribute to phenotype variations of 22q11.2 microdeletion/duplication syndromes as genomic modifiers.

  5. Correlations between identical pions produced in the π-p interaction at 11.2 GeV/c

    International Nuclear Information System (INIS)

    Tirelli, Marco.

    1977-01-01

    The existence of correlations between identical pion pairs created by the π - p interaction at 11.2 GeV.c was shown. This correlation shows itself by helping the emissions of pion pairs having the same momentum and may be interpreted as being the result of the interference between pion emissions by oscillations spread over the surface of a sphere. The quantitative analysis of this effect makes it possible to estimate at (1.04 +- 0.011)Fm the radius R of the interaction area and at (0.41 +- 0.11) Fm the thickness delta of the layer inside which the pions are emitted. This latter parameter may also be interpreted as being the mean life of the source which would appear to be Tau = (1.35 +- 0.35)10 -24 sec. An endeavour was made to study the shape of the interaction area by estimating the value of R for different observation directions. The results, subject to confirmation with higher statistics, seem to indicate that the interaction area might be spherical in shape. The value of the delta parameter under that of R agrees with Cocconi's hypothesis, according to which the pions are considered to be emitted from a spherical layer of area R and of delta depth. This delta parameter interpreted as the path taken by the light during the interaction time makes it possible to conclude that all points of the interaction and Podgoretsky's model, which presupposes interference between the emissions of pions by oscillators distributed over all the surface of the sphere, is ill suited to the description of the phenomenon [fr

  6. An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome

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    František Váša

    2016-01-01

    Full Text Available Chromosome 22q11.2 deletion syndrome (22q11DS is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes, we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure as the affected core (A-core of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs — chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, “de-centralizing” the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30–40% of 22q11DS patients develop.

  7. Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome

    Directory of Open Access Journals (Sweden)

    Maria eJalbrzikowski

    2014-11-01

    Full Text Available 22q11.2 Microdeletion Syndrome (22q11DS is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: 1 differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI measures within white matter tracts; 2 whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and 3 relationships between DTI measures, social cognition task performance and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls. We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA, axial (AD and radial diffusivity (RD, using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the inferior fronto-occipital fasciculus in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to

  8. Proline and COMT status affect visual connectivity in children with 22q11.2 deletion syndrome.

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    Maurice J C M Magnée

    Full Text Available BACKGROUND: Individuals with the 22q11.2 deletion syndrome (22q11DS are at increased risk for schizophrenia and Autism Spectrum Disorders (ASDs. Given the prevalence of visual processing deficits in these three disorders, a causal relationship between genes in the deleted region of chromosome 22 and visual processing is likely. Therefore, 22q11DS may represent a unique model to understand the neurobiology of visual processing deficits related with ASD and psychosis. METHODOLOGY: We measured Event-Related Potentials (ERPs during a texture segregation task in 58 children with 22q11DS and 100 age-matched controls. The C1 component was used to index afferent activity of visual cortex area V1; the texture negativity wave provided a measure for the integrity of recurrent connections in the visual cortical system. COMT genotype and plasma proline levels were assessed in 22q11DS individuals. PRINCIPAL FINDINGS: Children with 22q11DS showed enhanced feedforward activity starting from 70 ms after visual presentation. ERP activity related to visual feedback activity was reduced in the 22q11DS group, which was seen as less texture negativity around 150 ms post presentation. Within the 22q11DS group we further demonstrated an association between high plasma proline levels and aberrant feedback/feedforward ratios, which was moderated by the COMT(158 genotype. CONCLUSIONS: These findings confirm the presence of early visual processing deficits in 22q11DS. We discuss these in terms of dysfunctional synaptic plasticity in early visual processing areas, possibly associated with deviant dopaminergic and glutamatergic transmission. As such, our findings may serve as a promising biomarker related to the development of schizophrenia among 22q11DS individuals.

  9. Molecular analysis of DiGeorge Syndrome-related translocation breakpoints in 22q11.2

    Energy Technology Data Exchange (ETDEWEB)

    Chieffo, C.; Barnoski, B.L.; Emanuel, B.S. [Children`s Hospital of Philadelphia, PA (United States)] [and others

    1994-09-01

    22q11 demonstrates a high frequency of disease-specific rearrangements. Several of the rearrangements are associated with developmental abnormalities such as DiGeorge Syndrome (DGS), Velocardiofacial Syndrome (VCFS), Cat Eye Syndrome (CES) and Supernumerary der(22)t(11;22) Syndrome. DGS and VCFS involve deletions of 22q11.2 resulting from unbalanced translocations or microdeletions. In contrast, CES and Supernumerary der(22)t(11;22) Syndrome result from duplications of this region via inter- or intra- chromosomal exchange. Although the molecular mechanism giving rise to these rearrangements has yet to be elucidated, the presence of known 22q11 repetitive elements are likely to be involved. GM5878 is a 46,XY,t(10;22) cell line from a balanced translocation carrier father of an unbalanced DGS patient. GM0980 is a cell line from a patient with features of DGS/VCFS with an unbalanced karyotype. Using FISH cosmids, we have localized these translocation breakpoints near pH160b (D22S66) which maps to the center of the DiGeorge chromosomal region (DGCR). To further localize the breakpoint of GM5878, overlapping cosmids spanning this region were used as probes for FISH. Use of additional overlapping cosmids allowed the sublocalization of the breakpoint to a 10kb region. A 4.8 kb BglII fragment predicted to cross the breakpoint was isolated. When this fragment was used as a probe to normal and GM5878 DNA, novel bands were detected in GM5878 DNA digested with EcoRI and BglII. Similar analysis of the GM0980 breakpoint is being pursued. Full molecular characterization of these translocations is in progress using inverse PCR to clone the junctional fragments for sequencing. Detailed analysis of the region may reveal molecular features which make this a rearrangement prone area of the genome and help elucidate its relationship to human cytogenetic disease.

  10. Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development

    Science.gov (United States)

    Meechan, Daniel W.; Maynard, Thomas M.; Fernandez, Alejandra; Karpinski, Beverly A.; Rothblat, Lawrence A.; LaMantia, Anthony S.

    2015-01-01

    Understanding the developmental etiology of autistic spectrum disorders, attention deficit/hyperactivity disorder and schizophrenia remains a major challenge for establishing new diagnostic and therapeutic approaches to these common, difficult-to-treat diseases that compromise neural circuits in the cerebral cortex. One aspect of this challenge is the breadth and overlap of ASD, ADHD, and SCZ deficits; another is the complexity of mutations associated with each, and a third is the difficulty of analyzing disrupted development in at-risk or affected human fetuses. The identification of distinct genetic syndromes that include behavioral deficits similar to those in ASD, ADHC and SCZ provides a critical starting point for meeting this challenge. We summarize clinical and behavioral impairments in children and adults with one such genetic syndrome, the 22q11.2 Deletion Syndrome, routinely called 22q11DS, caused by micro-deletions of between 1.5 and 3.0 MB on human chromosome 22. Among many syndromic features, including cardiovascular and craniofacial anomalies, 22q11DS patients have a high incidence of brain structural, functional, and behavioral deficits that reflect cerebral cortical dysfunction and fall within the spectrum that defines ASD, ADHD, and SCZ. We show that developmental pathogenesis underlying this apparent genetic “model” syndrome in patients can be defined and analyzed mechanistically using genomically accurate mouse models of the deletion that causes 22q11DS. We conclude that “modeling a model”, in this case 22q11DS as a model for idiopathic ASD, ADHD and SCZ, as well as other behavioral disorders like anxiety frequently seen in 22q11DS patients, in genetically engineered mice provides a foundation for understanding the causes and improving diagnosis and therapy for these disorders of cortical circuit development. PMID:25866365

  11. Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome.

    Science.gov (United States)

    Jalbrzikowski, Maria; Villalon-Reina, Julio E; Karlsgodt, Katherine H; Senturk, Damla; Chow, Carolyn; Thompson, Paul M; Bearden, Carrie E

    2014-01-01

    22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk.

  12. Categorical versus dimensional approaches to autism-associated intermediate phenotypes in 22q11.2 microdeletion syndrome.

    Science.gov (United States)

    Jalbrzikowski, Maria; Ahmed, Khwaja Hamzah; Patel, Arati; Jonas, Rachel; Kushan, Leila; Chow, Carolyn; Bearden, Carrie E

    2017-01-01

    22q11.2 Microdeletion syndrome (22q11DS) is associated with elevated rates of autism spectrum disorders (ASDs), although the diagnosis is controversial. In order to determine whether there is a biological substrate of ASD in 22q11DS, we examined neurocognitive and structural neuroanatomic differences between those with 22q11DS and an ASD diagnosis (22q11DS-ASD+) and those with 22q11DS without ASD (22q11DS-ASD-); we then determined whether these differences were better characterized within a categorical or dimensional framework. We collected multiple neurocognitive measures and high-resolution T1-weighted scans on 116 individuals (29 22q11DS-ASD+, 32 22q11DS-ASD-, 55 typically developing controls) between 6 and 26 years of age. Measures of subcortical volume, cortical thickness (CT), and surface area were extracted using the FreeSurfer image analysis suite. Group differences in neurocognitive and neuroanatomic measures were assessed; regression analyses were then performed to determine whether a categorical or dimensional measure of ASD was a better predictor of neurocognitive impairment and/or neuroanatomic abnormalities observed in 22q11DS-ASD+. In comparison to 22q11DS-ASD-, 22q11DS-ASD+ participants exhibited decreased bilateral hippocampal CT and decreased right amygdala volumes. Those with 22q11DS-ASD+ also showed slowed processing speed and impairments in visuospatial and facial memory. Neurocognitive impairments fit a dimensional model of ASD, whereas reductions in parahippocampal CT were best explained by a categorical measure of ASD. A combination of categorical and dimensional measures of ASD may provide the most comprehensive understanding of ASDs in 22q11DS.

  13. Evidence of the impact of visuo-spatial processing on magnitude representation in 22q11.2 microdeletion syndrome.

    Science.gov (United States)

    Attout, Lucie; Noël, Marie-Pascale; Vossius, Line; Rousselle, Laurence

    2017-05-01

    The influence of visuo-spatial skills on numerical magnitude processing is the subject of a long-standing debate. As most of the numerical and non-numerical magnitude abilities underpinning mathematical development are visual by nature, they are often assessed in the visual modality, thereby confusing visuo-spatial and numerical processing. In order to assess the influence of visuo-spatial processing on numerical magnitude representation, we examined magnitude processing in patients with 22q11.2 deletion syndrome (22q11DS), a genetic condition characterized by a cognitive profile with a relative weakness in visuo-spatial abilities but with preserved verbal abilities. Twenty-seven participants with 22q11DS were compared to two control groups (one matched on verbal intelligence and the other on visuo-spatial abilities) on several magnitude comparison tasks each with different visuo-spatial processing requirements. Our results showed that participants with 22q11DS present a consistent pattern of impairment in magnitude comparison tasks requiring the processing of visuo-spatial dimensions: comparison of lengths and collections. In contrast, their performance did not differ from the control groups in a visual task with no spatial processing requirement (i.e. numerical comparison of flashed dot sequences) or in auditory tasks (i.e., duration comparison and numerical comparison of sound sequences). Finally, a specific deficit of enumeration processes was observed in the subitizing range. Taken together, these results show that deficits in magnitude can occur as a consequence of a visuo-spatial deficit. This highlights the influence of the nature of the tasks selected to assess magnitude representation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Frequency of 22q11.2 microdeletion in sporadic non-syndromic tetralogy of Fallot cases.

    Science.gov (United States)

    Gioli-Pereira, L; Pereira, A C; Bergara, D; Mesquita, S; Lopes, A A; Krieger, J E

    2008-06-06

    Tetralogy of Fallot (TOF) is a congenital conotruncal heart defect commonly found in DiGeorge (DGS) and velocardiofacial (VCFS) syndromes. The deletion of chromosome 22q11 has also been demonstrated in sporadic or familial cases of TOF. The aim of the present study was to investigate the frequency of del22q11 in patients with non-syndromic TOF seen at a tertiary Pediatric Cardiology care center. One hundred and twenty three non-syndromic TOF patients were selected and evaluated by history, physical examination and review of medical records. Venous blood was drawn for genomic DNA extraction after informed consent 22q11 microdeletion diagnosis was conducted through a standardized SNP genotyping assay and consecutive homozygosity mapping. Phenotype-genotype correlations regarding cardiac anatomy were conducted. We evaluated 123 non-syndromic TOF patients for a 22q11 deletion. 105 (85.4%) patients presented pulmonary stenosis and 18 (14.6%) had pulmonary atresia. Eight patients (6.5%) were found to have a deletion. Of the deleted patients, three (37.5%) presented pulmonary atresia. We have verified a tendency towards a higher prevalence of pulmonary atresia when comparing TOF patients with and without 22q11 microdeletion. 22q11.2 deletion in non-syndromic TOF patients is present in approximately 6% of patients. We suggest a tendency towards a higher prevalence of pulmonary atresia in non-syndromic TOF patients with 22q11 microdeletion. Molecular genetic screening of non-syndromic TOF patient may be important for the correct care of these patients and a more specific genetic diagnostic and counseling.

  15. Summary of surface-water-quality data collected for the Northern Rockies Intermontane Basins National Water-Quality Assessment Program in the Clark Fork-Pend Oreille and Spokane River basins, Montana, Idaho, and Washington, water years 1999-2001

    Science.gov (United States)

    Beckwith, Michael A.

    2003-01-01

    Water-quality samples were collected at 10 sites in the Clark Fork-Pend Oreille and Spokane River Basins in water years 1999 – 2001 as part of the Northern Rockies Intermontane Basins (NROK) National Water-Quality Assessment (NAWQA) Program. Sampling sites were located in varied environments ranging from small streams and rivers in forested, mountainous headwater areas to large rivers draining diverse landscapes. Two sampling sites were located immediately downstream from the large lakes; five sites were located downstream from large-scale historical mining and oreprocessing areas, which are now the two largest “Superfund” (environmental remediation) sites in the Nation. Samples were collected during a wide range of streamflow conditions, more frequently during increasing and high streamflow and less frequently during receding and base-flow conditions. Sample analyses emphasized major ions, nutrients, and selected trace elements. Streamflow during the study ranged from more than 130 percent of the long-term average in 1999 at some sites to 40 percent of the long-term average in 2001. River and stream water in the study area exhibited small values for specific conductance, hardness, alkalinity, and dissolved solids. Dissolved oxygen concentrations in almost all samples were near saturation. Median total nitrogen and total phosphorus concentrations in samples from most sites were smaller than median concentrations reported for many national programs and other NAWQA Program study areas. The only exceptions were two sites downstream from large wastewater-treatment facilities, where median concentrations of total nitrogen exceeded the national median. Maximum concentrations of total phosphorus in samples from six sites exceeded the 0.1 milligram per liter threshold recommended for limiting nuisance aquatic growth. Concentrations of arsenic, cadmium, copper, lead, mercury, and zinc were largest in samples from sites downstream from historical mining and ore

  16. Risk of Psychiatric Disorders Among Individuals With the 22q11.2 Deletion or Duplication: A Danish Nationwide, Register-Based Study.

    Science.gov (United States)

    Hoeffding, Louise K; Trabjerg, Betina B; Olsen, Line; Mazin, Wiktor; Sparsø, Thomas; Vangkilde, Anders; Mortensen, Preben B; Pedersen, Carsten B; Werge, Thomas

    2017-03-01

    Microdeletions and duplications have been described at the 22q11.2 locus. However, little is known about the clinical and epidemiologic consequences at the population level. To identify indicators of deletions or duplications at the 22q11.2 locus and estimate the incidence rate ratios (IRRs) and absolute risk for psychiatric disorders in clinically identified individuals with 22q11.2 deletion or duplication. A Danish nationwide register study including all individuals recorded in the Danish Cytogenetic Central Register with a 22q11.2 deletion or duplication was performed. A total of 3 768 943 individuals born in Denmark from 1955 to 2012 were followed up during the study period (total follow-up, 57.1 million person-years). Indicators of 22q11.2 deletion or duplication and cumulative incidences were estimated using a nested case-control design that included individuals from the population-based cohort. Survival analysis was used to compare risk of disease in individuals with and without the 22q11.2 deletion or duplication. The study was conducted from May 7, 2015, to August 14, 2016. The 22q11.2 deletion or duplication. Indicators for carrying a 22q11.2 deletion or duplication, IRR, and cumulative incidences for psychiatric diagnoses (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, codes F00-F99), including schizophrenia-spectrum disorders, mood disorders, neurotic stress-related and somatoform disorders, and a range of developmental and childhood disorders. Among the 3 768 943 participants, 244 (124 [50.8%] male) and 58 (29 [50.0%] male) individuals were clinically identified with a 22q11.2 deletion or duplication, respectively. Mean (SD) age at diagnosis of any psychiatric disorder was 12.5 (8.3) years for individuals with deletions and 6.1 (0.9) years for duplication carriers. A parental diagnosis of schizophrenia-but not of other psychiatric diagnoses-was associated with a 22q11.2 deletion, and parental

  17. Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.

    Science.gov (United States)

    Carmel, Miri; Zarchi, Omer; Michaelovsky, Elena; Frisch, Amos; Patya, Miriam; Green, Tamar; Gothelf, Doron; Weizman, Abraham

    2014-09-01

    The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. A pilot study on immuno-psychiatry in the 22q11.2 deletion syndrome: a role for Th17 cells in psychosis?

    Science.gov (United States)

    Vergaelen, Elfi; Schiweck, Carmen; Van Steeland, Kristof; Counotte, Jacqueline; Veling, Wim; Swillen, Ann; Drexhage, Hemmo; Claes, Stephan

    2018-03-19

    A growing body of evidence supports a role for immune alterations in Schizophrenia Spectrum Disorders (SSD). A high prevalence (25% - 40%) of SSD has been found in patients with 22q11.2 deletion syndrome (22q11.2DS), which is known for T-cell deficits due to thymus hypoplasia. This study is the first to explore the association between the T-cell subsets and psychotic symptoms in adults with 22q11.2DS. 34 individuals (aged 19-38 yrs.) with 22q11.2DS and 34 healthy age- and gender matched control individuals were included. FACS analysis of the blood samples was performed to define T-cell subsets. Ultra-high risk for psychosis or diagnosis of SSD was determined based on CAARMS interviews and DSM-5 criteria for SSD. Positive psychotic symptom severity was measured based on the PANSS positive symptoms subscale. A partial T-cell immune deficiency in 22q11.2DS patients was confirmed by significantly reduced percentages of circulating T and T-helper cells. Significantly higher percentages of inflammatory Th1, Th17, and memory T-helper cells were found in adults with 22q11.2DS. Most importantly an increased Th17 percentage was found in adults with psychotic symptoms as compared to non-psychotic adults with 22q11.2DS, and Th17 percentage were related to the presence of positive psychotic symptoms. Given the literature on the role of T cells and in particular of Th17 cells and IL-17 in hippocampus development, cognition and behavior, these results support the hypothesis for a role of Th17 cells in the development and/or regulation of psychotic symptoms in 22q11.2DS. This pilot study underlines the importance to further study the role of T-cell defects and of Th17 cells in the development of psychiatric symptoms. It also supports the possibility to use 22q11.2DS as a model to study T-cell involvement in the development of SSD. Copyright © 2018. Published by Elsevier Inc.

  19. Eating in the absence of hunger but not loss of control behaviors are associated with 16p11.2 deletions.

    Science.gov (United States)

    Gill, Richard; Chen, Qixuan; D'Angelo, Debra; Chung, Wendy K

    2014-12-01

    The ∼600-kb BP4-BP5 16p11.2 deletion has been consistently associated with obesity. We studied two heritable disinhibited eating behaviors, eating in the absence of hunger (EAH) and loss of control (LOC), to better characterize the relationship between the deletion and obesity. Our study population included ninety-three 16p11.2 CNV carriers (64 with deletions and 29 with duplications) and their families. We performed analyses using linear mixed models and focused on deletion carriers. We confirmed previous associations between the 16p11.2 deletion and obesity (P affect. Conditioning BMI on the 16p11.2 deletion and each EAH behavior did not abolish the association between the deletion and obesity. LOC was underrepresented and not associated with the deletion. We report evidence that the 16p11.2 deletion may influence specific obesity-associated disinhibited eating behaviors: EAH due to external trigger and EAH due to boredom. Prospective studies are needed to confirm the temporal order of EAH behaviors and obesity related to the deletion. © 2014 The Obesity Society.

  20. Dosage of copy number variation at 22q11.2 mediates changes in cognition, social function and brain structure in autism spectrum disorder.

    Science.gov (United States)

    Chen, Hsin-I; Chien, Yi-Ling; Liao, Hsio-Mei; Chien, Wei-Hsien; Chen, Chia-Hsiang; Chen, Yu-Chieh; Gau, Susan Shur-Fen

    2016-07-01

    Microdeletion at 22q11.2, a common copy number variation (CNV) noted in neurodevelopmental disorders, may be associated with cognitive impairment. However, cognitive function in individuals with microduplication remains unclear. This work presents the genetic, clinical, and brain structural data of two men out of 335 probands with autistic spectrum disorder (ASD) who had different CNV dosages at 22q11.2, and comparison with their siblings, 55 ASD probands, and 73 controls. Both showed severe autistic symptoms, but the proband with microduplication demonstrated better cognitive functions. Furthermore, different cingulate gyrus volume changes were noted, indicating that the proband with 22q11.2 microduplication had a different pattern of cingulate gyrus structure. Our comprehensive characterization of the behavioral, cognitive, and imaging phenotypes of ASD probands with different CNV dosage at 22q11.2 contribute to how copy number changes at 22q11.2 mediate the phenotypes in ASD, and pave the way for future clinical and functional study on these variants. Copyright © 2016. Published by Elsevier B.V.

  1. MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review

    Directory of Open Access Journals (Sweden)

    Andreas J. eForstner

    2013-12-01

    Full Text Available The 22q11.2 deletion is the strongest known genetic risk factor for schizophrenia. Research has implicated microRNA-mediated dysregulation in 22q11.2 deletion syndrome (22q11.2DS schizophrenia risk. Primary candidate genes are DGCR8, which encodes a component of the microprocessor complex essential for microRNA biogenesis, and MIR185, which encodes microRNA 185. Mouse models of 22q11.2DS have demonstrated alterations in brain microRNA biogenesis, and that DGCR8 haploinsufficiency may contribute to these alterations, e.g. via downregulation of a specific microRNA subset. miR-185 was the top-scoring down-regulated microRNA in both the prefrontal cortex and the hippocampus, brain areas which are the key foci of schizophrenia research. This reduction in miR-185 expression contributed to dendritic and spine development deficits in hippocampal neurons. In addition, miR-185 has two validated targets (RhoA, Cdc42, both of which have been associated with altered expression levels in schizophrenia. These combined data support the involvement of miR-185 and its down-stream pathways in schizophrenia.This review summarizes evidence implicating microRNA-mediated dysregulation in schizophrenia in both 22q11.2DS-related and idiopathic cases.

  2. Validation of a SNP-based non-invasive prenatal test to detect the fetal 22q11.2 deletion in maternal plasma samples.

    Science.gov (United States)

    Ravi, Harini; McNeill, Gabriel; Goel, Shruti; Meltzer, Steven D; Hunkapiller, Nathan; Ryan, Allison; Levy, Brynn; Demko, Zachary P

    2018-01-01

    Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma has been widely adopted. Recently, NIPT coverage has expanded to detect subchromosomal abnormalities including the 22q11.2 deletion. Validation of a SNP-based NIPT for detection of 22q11.2 deletions demonstrating a high sensitivity (97.8%) and specificity (99.75%) has been reported. We sought to further demonstrate the performance of a revised version of the test in a larger set of pregnancy plasma samples. Blood samples from pregnant women (10 with 22q11.2-deletion‒affected fetuses and 390 negative controls) were successfully analyzed using a revised SNP-based NIPT for the 22q11.2 deletion. The sensitivity and specificity of the assay were measured. Sensitivity of the assay was 90% (9/10), and specificity of the assay was 99.74% (389/390), with a corresponding false positive-rate of 0.26%. The data presented in this study add to the growing body of evidence demonstrating the ability of the SNP-based NIPT to detect 22q11.2 deletions with high sensitivity and specificity.

  3. Schizophrenia Spectrum Disorders in a Danish 22q11.2 Deletion Syndrome Cohort Compared to the Total Danish Population—A Nationwide Register Study

    Science.gov (United States)

    Vangkilde, Anders; Olsen, Line; Hoeffding, Louise K.; Pedersen, Carsten B.; Mortensen, Preben B.; Werge, Thomas; Trabjerg, Betina

    2016-01-01

    Objective: Cross-sectional studies have shown associations between 22q11.2 deletion syndrome and schizophrenia. However, large-scale prospective studies have been lacking. We, therefore, conducted the first large-scale population based study on the risk of being diagnosed with schizophrenia in persons identified with 22q11.2 deletion syndrome. Methods: Danish nationwide registers were linked to establish a cohort consisting of all Danish citizens born during 1955–2004 and the cohort was followed from January 1, 1994 until December 31, 2013. Data were analyzed using survival analyses and adjusted for calendar year, age, sex, and parental mental health history. Results: A total of 156 individuals with 22q11.2 deletion syndrome were identified, out of which 6 individuals were diagnosed with schizophrenia spectrum disorders following identification with 22q11 deletion syndrome. Identified carriers of 22q11.2 deletion had an 8.13(95% CI: 3.65–18.09) fold increased risk of schizophrenia spectrum disorder. Conclusions: Carriers of a 22q11.2 deletion who had been clinically identified had a highly increased risk of schizophrenia spectrum disorders. PMID:26738530

  4. Developmental excitatory-to-inhibitory GABA-polarity switch is disrupted in 22q11.2 deletion syndrome: a potential target for clinical therapeutics.

    Science.gov (United States)

    Amin, Hayder; Marinaro, Federica; De Pietri Tonelli, Davide; Berdondini, Luca

    2017-11-16

    Individuals with 22q11.2 microdeletion syndrome (22q11.2 DS) show cognitive and behavioral dysfunctions, developmental delays in childhood and risk of developing schizophrenia and autism. Despite extensive previous studies in adult animal models, a possible embryonic root of this syndrome has not been determined. Here, in neurons from a 22q11.2 DS mouse model (Lgdel +/- ), we found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels. We demonstrate with large-scale spiking activity recordings a concurrent deregulation of the spontaneous network activity and homeostatic network plasticity. Additionally, Lgdel +/- networks at early development show abnormal neuritogenesis and void of synchronized spontaneous activity. Furthermore, parallel experiments on Dgcr8 +/- mouse cultures reveal a significant, yet not exclusive contribution of the dgcr8 gene to our phenotypes of Lgdel +/- networks. Finally, we show that application of bumetanide, an inhibitor of NKCC1, significantly decreases the hyper-excitable action of GABA A receptor signaling and restores network homeostatic plasticity in Lgdel +/- networks. Overall, by exploiting an on-a-chip 22q11.2 DS model, our results suggest a delayed GABA-switch in Lgdel +/- neurons, which may contribute to a delayed embryonic development. Prospectively, acting on the GABA-polarity switch offers a potential target for 22q11.2 DS therapeutic intervention.

  5. Effect of 22q11.2 deletion on bleeding and transfusion utilization in children with congenital heart disease undergoing cardiac surgery

    Science.gov (United States)

    Brenner, Michelle K.; Clarke, Shanelle; Mahnke, Donna K.; Simpson, Pippa; Bercovitz, Rachel S.; Tomita-Mitchell, Aoy; Mitchell, Michael E.; Newman, Debra K.

    2016-01-01

    Background Post-surgical bleeding causes significant morbidity and mortality in children undergoing surgery for congenital heart defects (CHD). 22q11.2 deletion syndrome (DS) is the second most common genetic risk factor for CHD. The deleted segment of chromosome 22q11.2 encompasses the gene encoding glycoprotein (GP) Ibβ, which is required for expression of the GPIb-V-IX complex on the platelet surface, where it functions as the receptor for von Willebrand factor (VWF). Binding of GPIb-V-IX to VWF is important for platelets to initiate hemostasis. It is not known whether hemizygosity for the gene encoding GPIbβ increases the risk for bleeding following cardiac surgery for patients with 22q11.2 DS. Methods We performed a case-control study of 91 pediatric patients who underwent cardiac surgery with cardiopulmonary bypass from 2004–2012 at Children’s Hospital of Wisconsin. Results Patients with 22q11.2 DS had larger platelets and lower platelet counts, bled more excessively and received more transfusion support with packed red blood cells in the early post-operative period relative to control patients. Conclusions Pre-surgical genetic testing for 22q11.2 DS may help to identify a subset of pediatric cardiac surgery patients who are at increased risk for excessive bleeding and who may require more transfusion support in the post-operative period. PMID:26492284

  6. Auxological evaluation in patients with a 22q11.2 microdeletion syndrome: normal prevalence of obesity and neonatal length and gender influence on body mass index evolution.

    Science.gov (United States)

    Reynaud, R; Derain-Court, J; Braunstein, D; Veyrat, M; Gaudart, J; Giuliano, F; Philip, N

    2011-01-01

    To evaluate auxological parameters in children and adults with a 22q11.2 microdeletion syndrome (22q11.2 DS) and to compare prevalence of obesity to that in the French general population. 102 patients with 22q11.2 DS (49 males, 53 females) were recruited from birth to adulthood through a reference center in southern France. Mean BMI Z score and mean height were normal (0.07 ± 1.49 SD, -0.87 ± 1.36 SDS, respectively). 16.1% of patients were overweight (including obese), 57% out of them being born small for gestational age for length versus 25% of non-overweight patients. During infancy, BMI increased in girls (+0.89 SD Z score). Childhood: 14.7% were overweight, prevalence similar to that of the in French children population. Adulthood: 19.2% were overweight. BMI Z scores were inversely correlated with neonatal length (p = 0.026) and female sex (p = 0.032) but positively associated with neonatal weight (p = 0.036). From analysis of neonatal data, 22q11.2 DS newborns were significantly shorter with regard to their weight (p 22q11.2 DS to that in the French population. The BMI Z score was inversely correlated with neonatal length and female gender but positively associated with neonatal weight. Copyright © 2011 S. Karger AG, Basel.

  7. Dosage of copy number variation at 22q11.2 mediates changes in cognition, social function and brain structure in autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Hsin-I Chen

    2016-07-01

    Full Text Available Microdeletion at 22q11.2, a common copy number variation (CNV noted in neurodevelopmental disorders, may be associated with cognitive impairment. However, cognitive function in individuals with microduplication remains unclear. This work presents the genetic, clinical, and brain structural data of two men out of 335 probands with autistic spectrum disorder (ASD who had different CNV dosages at 22q11.2, and comparison with their siblings, 55 ASD probands, and 73 controls. Both showed severe autistic symptoms, but the proband with microduplication demonstrated better cognitive functions. Furthermore, different cingulate gyrus volume changes were noted, indicating that the proband with 22q11.2 microduplication had a different pattern of cingulate gyrus structure. Our comprehensive characterization of the behavioral, cognitive, and imaging phenotypes of ASD probands with different CNV dosage at 22q11.2 contribute to how copy number changes at 22q11.2 mediate the phenotypes in ASD, and pave the way for future clinical and functional study on these variants.

  8. A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome.

    Science.gov (United States)

    Balci, S; Altugan, F S; Alehan, D; Aypar, E; Baltaci, V

    2009-01-01

    A prenatally sonographically diagnosed conotruncal anomaly with mosaic type trisomy 21 and 22q11.2 microdeletion/DiGeorge syndrome: We report a prenatally sonographically diagnosed conotruncal and urogenital anomaly. Postnatally, the patient presented with seizures, hypocalcemia, hypoparathyroidism and thymic aplasia and diagnosed as DiGeorge syndrome. Echocardiography showed malalignment VSD, supravalvular pulmonary stenosis and overriding aorta. Chromosome and FISH studies showed the association of mosaic type trisomy 21 and 22q11.2 microdeletion. The present patient is the second case of mosaic type of Down syndrome associated with 22q11.2 microdeletion. In addition the patient also had clinical and laboratory features of DiGeorge syndrome.

  9. Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome

    DEFF Research Database (Denmark)

    Didriksen, Michael; Fejgin, Kim; Nilsson, Simon R O

    2016-01-01

    in a wide range of other behavioural and biochemical assays. LIMITATIONS: The 22q11.2 microdeletion has incomplete penetrance in humans, and the severity of disease depends on the complete genetic makeup in concert with environmental factors. In order to obtain more marked phenotypes reflecting the severe...... conditions related to 22q11.2DS it is suggested to expose the Df(h22q11)/+ mice to environmental stressors that may unmask latent psychopathology. CONCLUSION: The Df(h22q11)/+ model will be a valuable tool for increasing our understanding of the etiology of schizophrenia and other psychiatric disorders......BACKGROUND: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. METHODS: We present a new mouse model (Df...

  10. Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome

    DEFF Research Database (Denmark)

    Didriksen, Michael; Fejgin, Kim; Nilsson, Simon R O

    2017-01-01

    in a wide range of other behavioural and biochemical assays. Limitations: The 22q11.2 microdeletion has incomplete penetrance in humans, and the severity of disease depends on the complete genetic makeup in concert with environmental factors. In order to obtain more marked phenotypes reflecting the severe...... conditions related to 22q11.2DS it is suggested to expose the Df(h22q11)/+ mice to environmental stressors that may unmask latent psychopathology. Conclusion: The Df(h22q11)/+ model will be a valuable tool for increasing our understanding of the etiology of schizophrenia and other psychiatric disorders......Background: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. Methods: We present a new mouse model (Df...

  11. Schizophrenia Spectrum Disorders in a Danish 22q11.2 Deletion Syndrome Cohort Compared to the Total Danish Population-A Nationwide Register Study

    DEFF Research Database (Denmark)

    Vangkilde, Anders; Olsen, Line; Hoeffding, Louise K

    2016-01-01

    OBJECTIVE: Cross-sectional studies have shown associations between 22q11.2 deletion syndrome and schizophrenia. However, large-scale prospective studies have been lacking. We, therefore, conducted the first large-scale population based study on the risk of being diagnosed with schizophrenia...... in persons identified with 22q11.2 deletion syndrome. METHODS: Danish nationwide registers were linked to establish a cohort consisting of all Danish citizens born during 1955-2004 and the cohort was followed from January 1, 1994 until December 31, 2013. Data were analyzed using survival analyses...... and adjusted for calendar year, age, sex, and parental mental health history. RESULTS: A total of 156 individuals with 22q11.2 deletion syndrome were identified, out of which 6 individuals were diagnosed with schizophrenia spectrum disorders following identification with 22q11 deletion syndrome. Identified...

  12. The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region at 17p11.2

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Toshiyuki; Arakawa, Yoshiki; Inazawa, Johji [Kyoto Prefectural Univ. of Medicine, Kyoto (Japan)] [and others

    1997-03-31

    Smith-Magenis syndrome (SAIS) is caused by a microdeletion of 17p11.2 and comprises developmental and growth delay, facial abnormalities, unusual behavior and sleep problems. This phenotype may be due to haploinsufficiency of several contiguous genes. The human brain finger protein gene (ZNF179), a member of the RING finger protein family, has been isolated and mapped to l7p11.2. FISH analyses of metaphase or interphase chromosomes of 6 patients with SMS show that ZNF179 was deleted in one of the 2 homologs (17p11.2), indicating a possible association of the defect of this gene with the pathogenesis of SMS. Furthermore, using a prophase FISH ordering system, we sublocalized ZNF179 proximally to LLGL which lies on the critical region for SMS. 27 refs., 2 figs.

  13. MicroRNA Profiling of Neurons Generated Using Induced Pluripotent Stem Cells Derived from Patients with Schizophrenia and Schizoaffective Disorder, and 22q11.2 Del

    Science.gov (United States)

    Zhao, Dejian; Lin, Mingyan; Chen, Jian; Pedrosa, Erika; Hrabovsky, Anastasia; Fourcade, H. Matthew; Zheng, Deyou; Lachman, Herbert M.

    2015-01-01

    We are using induced pluripotent stem cell (iPSC) technology to study neuropsychiatric disorders associated with 22q11.2 microdeletions (del), the most common known schizophrenia (SZ)-associated genetic factor. Several genes in the region have been implicated; a promising candidate is DGCR8, which codes for a protein involved in microRNA (miRNA) biogenesis. We carried out miRNA expression profiling (miRNA-seq) on neurons generated from iPSCs derived from controls and SZ patients with 22q11.2 del. Using thresholds of p22q11.2 del region. In addition, a nominally significant increase in the expression of several miRNAs was found in the 22q11.2 neurons that were previously found to be differentially expressed in autopsy samples and peripheral blood in SZ and autism spectrum disorders (e.g., miR-34, miR-4449, miR-146b-3p, and miR-23a-5p). Pathway and function analysis of predicted mRNA targets of the differentially expressed miRNAs showed enrichment for genes involved in neurological disease and psychological disorders for both up and down regulated miRNAs. Our findings suggest that: i. neurons with 22q11.2 del recapitulate the miRNA expression patterns expected of 22q11.2 haploinsufficiency, ii. differentially expressed miRNAs previously identified using autopsy samples and peripheral cells, both of which have significant methodological problems, are indeed disrupted in neuropsychiatric disorders and likely have an underlying genetic basis. PMID:26173148

  14. Detecting 22q11.2 deletions by use of multiplex ligation-dependent probe amplification on DNA from neonatal dried blood spot samples

    DEFF Research Database (Denmark)

    Sørensen, Karina; Agergaard, Peter Juul; Olesen, Charlotte

    2010-01-01

    of 22q11.2 deletions among certain manifestations, eg, congenital heart disease, on selected Danes, a multiplex ligation-dependant probe amplification (MLPA) analysis was designed. The analysis was planned to be performed on DNA extracted from dried blood spot samples (DBSS) obtained from Guthrie cards...... probe design is successful and reliable using minimal amounts of DNA. This allows for use of DBSS samples in a retrospective study of 22q11.2 deletion among certain manifestations associated with DiGeorge Syndrome....

  15. Isolation and genetic characterization of human coronavirus NL63 in primary human renal proximal tubular epithelial cells obtained from a commercial supplier, and confirmation of its replication in two different types of human primary kidney cells.

    Science.gov (United States)

    Lednicky, John A; Waltzek, Thomas B; McGeehan, Elizabeth; Loeb, Julia C; Hamilton, Sara B; Luetke, Maya C

    2013-06-27

    Cryopreserved primary human renal proximal tubule epithelial cells (RPTEC) were obtained from a commercial supplier for studies of Simian virus 40 (SV40). Within twelve hrs after cell cultures were initiated, cytoplasmic vacuoles appeared in many of the RPTEC. The RPTEC henceforth deteriorated rapidly. Since SV40 induces the formation of cytoplasmic vacuoles, this batch of RPTEC was rejected for the SV40 study. Nevertheless, we sought the likely cause(s) of the deterioration of the RPTEC as part of our technology development efforts. Adventitious viruses in the RPTEC were isolated and/or detected and identified by isolation in various indicator cell lines, observation of cytopathology, an immunoflurorescence assay, electron microscopy, PCR, and sequencing. Cytomegalovirus (CMV) was detected in some RPTEC by cytology, an immunofluorescence assay, and PCR. Human Herpesvirus 6B was detected by PCR of DNA extracted from the RPTEC, but was not isolated. Human coronavirus NL63 was isolated and identified by RT-PCR and sequencing, and its replication in a fresh batch of RPTEC and another type of primary human kidney cells was confirmed. At least 3 different adventitious viruses were present in the batch of contaminated RPTEC. Whereas we are unable to determine whether the original RPTEC were pre-infected prior to their separation from other kidney cells, or had gotten contaminated with HCoV-NL63 from an ill laboratory worker during their preparation for commercial sale, our findings are a reminder that human-derived biologicals should always be considered as potential sources of infectious agents. Importantly, HCoV-NL63 replicates to high titers in some primary human kidney cells.

  16. Deletion of UBE3A in brothers with Angelman syndrome at the breakpoint with an inversion at 15q11.2.

    Science.gov (United States)

    Kuroda, Yukiko; Ohashi, Ikuko; Saito, Toshiyuki; Nagai, Jun-Ichi; Ida, Kazumi; Naruto, Takuya; Wada, Takahito; Kurosawa, Kenji

    2014-11-01

    Angelman syndrome (AS) is characterized by severe intellectual disability with ataxia, epilepsy, and behavioral uniqueness. The underlining molecular deficit is the absence of the maternal copy of the imprinted UBE3A gene due to maternal deletions, which is observed in 70-75% of cases, and can be detected using fluorescent in situ hybridization (FISH) of the UBE3A region. Only a few familial AS cases have been reported with a complete deletion of UBE3A. Here, we report on siblings with AS caused by a microdeletion of 15q11.2-q12 encompassing UBE3A at the breakpoint of an inversion at 15q11.2 and 15q26.1. Karyotyping revealed an inversion of 15q, and FISH revealed the deletion of the UBE3A region. Array comparative genomic hybridization (CGH) demonstrated a 467 kb deletion at 15q11.2-q12, encompassing only UBE3A, SNORD115, and PAR1, and a 53 kb deletion at 15q26.1, encompassing a part of SLCO3A1. Their mother had a normal karyotype and array CGH detected no deletion of 15q11.2-q12, so we assumed gonadal mosaicism. This report describes a rare type of familial AS detected using the D15S10 FISH test. © 2014 Wiley Periodicals, Inc.

  17. The Immune Signaling Adaptor LAT Contributes to the Neuroanatomical Phenotype of 16p11.2 BP2-BP3 CNVs

    NARCIS (Netherlands)

    Loviglio, Maria Nicla; Arbogast, Thomas; Jønch, Aia Elise; Collins, Stephan C.; Popadin, Konstantin; Bonnet, Camille S.; Giannuzzi, Giuliana; Maillard, Anne M.; Jacquemont, Sébastien; Loviglio, Maria Nicla; Jønch, Aia Elise; Popadin, Konstantin; Giannuzzi, Giuliana; Maillard, Anne M.; Fagerberg, Christina; Andersen, Charlotte Brasch; Doco-Fenzy, Martine; Delrue, Marie-Ange; Faivre, Laurence; Arveiler, Benoit; Geneviève, David; Schneider, Anouck; Gerard, Marion; Andrieux, Joris; El Chehadeh, Salima; Schaefer, Elise; Depienne, Christel; Van Haelst, Mieke; Brilstra, Eva H.; Van Binsbergen, Ellen; van Harssel, Jeske; van der Veken, Lars T.; Gusella, James F; Shen, Yiping; Mitchell, Elyse; Kini, Usha; Hawkes, Lara; Campbell, Carolyn; Butschi, Florence Niel; Addor, Marie Claude; Beckmann, Jacques S.; Jacquemont, Sébastien; Reymond, Alexandre; Yalcin, Binnaz; Katsanis, Nicholas; Golzio, Christelle; Reymond, Alexandre

    2017-01-01

    Copy-number changes in 16p11.2 contribute significantly to neuropsychiatric traits. Besides the 600 kb BP4-BP5 CNV found in 0.5%–1% of individuals with autism spectrum disorders and schizophrenia and whose rearrangement causes reciprocal defects in head size and body weight, a second distal 220 kb

  18. Social Cognition Dysfunction in Adolescents with 22q11.2 Deletion Syndrome (Velo-Cardio-Facial Syndrome): Relationship with Executive Functioning and Social Competence/Functioning

    Science.gov (United States)

    Campbell, L. E.; McCabe, K. L.; Melville, J. L.; Strutt, P. A.; Schall, U.

    2015-01-01

    Background: Social difficulties are often noted among people with intellectual disabilities. Children and adults with 22q.11.2 deletion syndrome (22q11DS) often have poorer social competence as well as poorer performance on measures of executive and social-cognitive skills compared with typically developing young people. However, the relationship…

  19. A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1.

    Science.gov (United States)

    Stevens, Servi J C; Blom, Eveline W; Siegelaer, Ingrid T J; Smeets, Eric E J G L

    2015-04-01

    We identified an identical and recurrent 9.4-Mbp deletion at chromosome bands 2p11.2-2p12, which occurred de novo in two unrelated patients. It is flanked at the distal and proximal breakpoints by two homologous segmental duplications consisting of low copy repeat (LCR) blocks in direct orientation, which have >99% sequence identity. Despite the fact that the deletion was almost 10 Mbp in size, the patients showed a relatively mild clinical phenotype, that is, mild-to-moderate intellectual disability, a happy disposition, speech delay and delayed motor development. Their phenotype matches with that of previously described patients. The 2p11.2-2p12 deletion includes the REEP1 gene that is associated with spastic paraplegia and phenotypic features related to this are apparent in most 2p11.2-2p12 deletion patients, but not in all. Other hemizygous genes that may contribute to the clinical phenotype include LRRTM1 and CTNNA2. We propose a recurrent but rare 2p11.2-2p12 deletion syndrome based on (1) the identical, non-random localisation of the de novo deletion breakpoints in two unrelated patients and a patient from literature, (2) the patients' phenotypic similarity and their phenotypic overlap with other 2p deletions and (3) the presence of highly identical LCR blocks flanking both breakpoints, consistent with a non-allelic homologous recombination (NAHR)-mediated rearrangement.

  20. A Common CYFIP1 Variant at the 15q11.2 Disease Locus Is Associated with Structural Variation at the Language-Related Left Supramarginal Gyrus

    NARCIS (Netherlands)

    Woo, Y.J.; Wang, T.; Guadalupe, T.M.; Nebel, R.A.; Vino, A.; Bene, V.A. Del; Molholm, S.; Ross, L.A.; Zwiers, M.P.; Fisher, S.E.; Foxe, J.J.; Abrahams, B.S.

    2016-01-01

    Copy number variants (CNVs) at the Breakpoint 1 to Breakpoint 2 region at 15q11.2 (BP1-2) are associated with language-related difficulties and increased risk for developmental disorders in which language is compromised. Towards underlying mechanisms, we investigated relationships between single