Restriction of the Patau syndrome to duplication of 13q22{yields}q.32 and possible role of interphase nuclear structure

Energy Technology Data Exchange (ETDEWEB)

Helali, A.N.; Jafolla, A.K.; Oumsiych, M.B. [Duke Univ. Medical Center, Durham, NC (United States)

1994-09-01

A 10-year-old white male presented with mild microcephaly, slight growth and psychomotor retardation, soft fleshy ears, and normal facial features except for thin lips. No other significant anomalies were reported except for tethered cord discovered at age 8 years. The karyotype was found to be 46,XY,der(18)t(13;18)(q32;p11.32)pat. The mild phenotype appears to be primarily due to the duplication of 13q32{yields}qter. None of the cardinal features of trisomy 13 are found in cases of duplication of bands 13q22 to qter. This case shows that Patau syndrome phenotype does not originate by duplication of 13q32{yields}qter and may thus be restricted to 13q22 to 13q32. The variability in phenotypes points to an alternative explanation to the classical one of additive and interactive gene effects. This model involves effects of changes in chromosome position in the interphase nucleus on gene expression.

Detection of chromosomal abnormalities and the 22q11 microdeletion in fetuses with congenital heart defects.

Science.gov (United States)

Lv, Wei; Wang, Shuyu

2014-11-01

Chromosomal abnormalities and the 22q11 microdeletion are implicated in congenital heart defects (CHDs). This study was designed to detect these abnormalities in fetuses and determine the effect of genetic factors on CHD etiology. Between January 2010 and December 2011, 113 fetuses with CHD treated at the Beijing Obstetrics and Gynecology Hospital were investigated, using chromosome karyotyping of either amniotic fluid cell or umbilical cord blood cell samples. Fetuses with a normal result were then investigated for the 22q11 microdeletion by fluorescence in situ hybridization. Of the 113 patients, 12 (10.6%) exhibited chromosomal abnormalities, while 6 (5.3%) of the remaining 101 cases presented with a 22q11 microdeletion. The incidence of chromosomal abnormalities was significantly higher in the group of fetuses presenting with extracardiac malformations in addition to CHD (Pheart defects should also be considered for 22q11 microdeletion detection to evaluate fetal prognosis, particularly prior to surgery.

Chromosome 22q11 in a Xhosa schizophrenia population | Koen ...

African Journals Online (AJOL)

Chromosome 22q11 aberrations substantially increase the risk for developing schizophrenia. Although micro-deletions in this region have been extensively investigated in different populations across the world, little is known of their prevalence in African subjects with schizophrenia. We screened 110 African ...

A rare balanced nonrobertsonian translocation involving acrocentric chromosomes: Chromosome abnormality of t(13;15(p11.2;q22.1

Directory of Open Access Journals (Sweden)

Dalvi Rupa

2016-01-01

Full Text Available BACKGROUND: Balanced non-robertsonian translocation (RT, involving acrocentric chromosomes, is a rare event and only a few cases are reported. Most of the RTs are balanced involving acrocentric chromosomes with the breakpoints (q10;q10. MATERIALS AND METHODS: Chromosome analysis was performed as per standard procedure – Giemsa-trypsin banding with 500 band resolution was analyzed for chromosome identification. RESULTS: In the present study, we report a rare balanced non-RTs involving chromosomes 13 and 15 with cytogenetic finding of 46, XX, t(13;15(p11.2;q22.1. CONCLUSION: To the best of our knowledge, this is the first such report of an unusual non-RT of t(13:15 with (p11.2;q22.1 break points.

Anterior pituitary failure (panhypopituitarism) with balanced chromosome translocation 46,XY,t(11;22)(q24;q13).

Science.gov (United States)

Yang, C Y; Chou, C W; Chen, S Y; Cheng, H M

2001-04-01

Hypopituitarism is the clinical syndrome that results from failure of the anterior pituitary gland to produce its hormones. Hypopituitarism can result from: (1) intrinsic or primary pituitary disease; (2) intrinsic hypothalamic or secondary pituitary disease; or (3) extrinsic extrasellar or parasellar disease. The etiologies of primary hypopituitarism are miscellaneous. The dominant clinical picture of hypopituitarism in the adult is that of hypogonadism. Reports have associated hypopituitarism with anti-pituitary-antibodies, hereditary syndrome and chromosome defects, but hypopituitarism has rarely been associated with balanced chromosome translocation (11;22)(q24;q13). Here, we describe a case of anterior pituitary failure with balanced chromosome translocation. A 19-year-old Chinese teenager presented with failure of pubertal development and sexual infantilism. On examination, the patient had the classic appearance of hypogonadism. Endocrine studies and three combined pituitary function tests revealed panhypopituitarism. A chromosomal study revealed 46,XY,t(11;22)(q24;q13), a balanced translocation between 11q24 and 22q13. Chest films showed delayed fusion of bilateral humeral head epiphyses and bilateral acromions. Scrotal sonography revealed testes were small bilaterally. Magnetic resonance imaging (MRI) of the sella revealed pituitary dwarfism. The patient received 19 months replacement therapy, including steroids (prednisolone 5 mg each day), L-thyroxine (Eltroxin 100 ug each day), and testosterone enanthate 250 mg every two weeks. His height increased 4 cm with secondary sexual characteristics developed, and muscle power increased.

Constitutional 11q14-q22 chromosome deletion syndrome in a child with neuroblastoma MYCN single copy.

Science.gov (United States)

Passariello, Annalisa; De Brasi, Daniele; Defferrari, Raffaella; Genesio, Rita; Tufano, Maria; Mazzocco, Katia; Capasso, Maria; Migliorati, Roberta; Martinsson, Tommy; Siani, Paolo; Nitsch, Lucio; Tonini, Gian Paolo

2013-11-01

Constitutional 11q deletion is a chromosome imbalance possibly found in MCA/MR patients analyzed for chromosomal anomalies. Its role in determining the phenotype depends on extension and position of deleted region. Loss of heterozygosity of 11q (region 11q23) is also associated with neuroblastoma, the most frequent extra cranial cancer in children. It represents one of the most frequent cytogenetic abnormalities observed in the tumor of patients with high-risk disease even if germline deletion of 11q in neuroblastoma is rare. Hereby, we describe a 18 months old girl presenting with trigonocephaly and dysmorphic facial features, including hypotelorism, broad depressed nasal bridge, micrognathia, synophrys, epicanthal folds, and with a stage 4 neuroblastoma without MYCN amplification, carrying a germline 11q deletion (11q14.1-q22.3), outside from Jacobsen syndrome and from neuroblastoma 11q critical regions. The role of 11q deletion in determining the clinical phenotype and its association with neuroblastoma development in the patient are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

Energy Technology Data Exchange (ETDEWEB)

D`Angelo, J.A.; Pillers, D.M.; Jett, P.L. [Oregon Health Sciences Univ. Portland, OR (United States)] [and others

1994-09-01

Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOF and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.

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

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

A 1.37-Mb 12p11.22-p11.21 deletion coincident with a 367-kb 22q11.2 duplication detected by array comparative genomic hybridization in an adolescent girl with autism and difficulty in self-care of menstruation.

Science.gov (United States)

Chen, Chih-Ping; Lin, Shuan-Pei; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Lee, Chen-Chi; Wang, Wayseen

2014-03-01

To present an array comparative genomic hybridization (aCGH) characterization of a 12p11.22-p11.21 microdeletion and 22q11.2 microduplication in an adolescent girl with autism, mental retardation, facial dysmorphism, microcephaly, behavior problems, and an apparently balanced reciprocal translocation of t(8;12)(q24.3;p11.2). A 13-year-old girl was referred to the hospital because of autism, mental retardation, and difficulty in the self-care of her menstruation. Cytogenetic analysis revealed an apparently balanced reciprocal translocation and a karyotype of 46,XX,t(8;12) (q24.3;p11.2)dn. The girl manifested microcephaly, hypertelorism, flat facial profile, prominent forehead, thick scalp hair, upslanting palpebral fissures, broad nasal bridge, bulbous nose, right simian crease, bilateral clinodactyly of the fifth fingers, bilateral pes cavus, learning difficulties, mental retardation, emotional instability, cognitive impairment, behavior problems, jumping-like gaits, and autistic spectrum disorder. aCGH was performed to evaluate genomic imbalance in this patient. aCGH analysis revealed a 1.37-Mb 12p11.22-p11.21 microdeletion or arr [hg 19] 12p11.22-p11.21 (30,645,008-32,014,774)×1 and a 367-kb 22q11.21 microduplication or arr [hg 19] 22q11.21 (18,657,470-19,024,306)×3. The 1.37-Mb 12p11.22-p11.21 microdeletion encompassed 26 genes including IPO8, CAPRIN2, and DDX11, and the 367-kb 22q11.21 microduplication encompassed 20 genes including USP18, DGCR6, PRODH, and DGCR2. An apparently balanced translocation may be in fact affected by concurrent deletion and duplication in two different chromosomal regions. Our presentation provides information on diagnostic phenotype of 12p11.22-p11.21 microdeletion and 22q11.2 microduplication. Copyright © 2014. Published by Elsevier B.V.

22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

Science.gov (United States)

Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

2017-04-01

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH. © 2017 Wiley Periodicals, Inc.

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…

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

Directory of Open Access Journals (Sweden)

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.

Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication.

Science.gov (United States)

Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E; Ventura, Mario

2008-01-01

Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Human bacterial artificial chromosome/p1 artificial chromosome probes spanning the length of chromosome 17 were used in FISH experiments on great apes, Old World monkeys and New World monkeys to study the evolutionary history of this chromosome. We observed that the macaque marker order represents the ancestral organization. Human, chimpanzee and gorilla homologous chromosomes differ by a paracentric inversion that occurred specifically in the Homo sapiens/Pan troglodytes/Gorilla gorilla ancestor. Detailed analyses of the paracentric inversion revealed that the breakpoints mapped to two regions syntenic to human 17q12/21 and 17q23, both rich in segmental duplications. Sequence analyses of the human and macaque organization suggest that the duplication events occurred in the catarrhine ancestor with the duplication blocks continuing to duplicate or undergo gene conversion during evolution of the hominoid lineage. We propose that the presence of these duplicons has mediated the inversion in the H. sapiens/P. troglodytes/G. gorilla ancestor. Recently, the same duplication blocks have been shown to be polymorphic in the human population and to be involved in triggering microdeletion and duplication in human. These results further support a model where genomic architecture has a direct role in both rearrangement involved in karyotype evolution and genomic instability in human.

Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures

Directory of Open Access Journals (Sweden)

Kesterson Robert A

2003-04-01

Full Text Available Abstract Background Chromosomal abnormalities affecting human chromosome 15q11-q13 underlie multiple genomic disorders caused by deletion, duplication and triplication of intervals in this region. These events are mediated by highly homologous segments of DNA, or duplicons, that facilitate mispairing and unequal cross-over in meiosis. The gene encoding an amyloid precursor protein-binding protein (APBA2 was previously mapped to the distal portion of the interval commonly deleted in Prader-Willi and Angelman syndromes and duplicated in cases of autism. Results We show that this gene actually maps to a more telomeric location and is partially duplicated within the broader region. Two highly homologous copies of an interval containing a large 5' exon and downstream sequence are located ~5 Mb distal to the intact locus. The duplicated copies, containing the first coding exon of APBA2, can be distinguished by single nucleotide sequence differences and are transcriptionally inactive. Adjacent to APBA2 maps a gene termed KIAA0574. The protein encoded by this gene is weakly homologous to a protein termed X123 that in turn maps adjacent to APBA1 on 9q21.12; APBA1 is highly homologous to APBA2 in the C-terminal region and is distinguished from APBA2 by the N-terminal region encoded by this duplicated exon. Conclusion The duplication of APBA2 sequences in this region adds to a complex picture of different low copy repeats present across this region and elsewhere on the chromosome.

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

De novo 12q22.q23.3 duplication associated with temporal lobe epilepsy.

Science.gov (United States)

Vari, Maria Stella; Traverso, Monica; Bellini, Tommaso; Madia, Francesca; Pinto, Francesca; Minetti, Carlo; Striano, Pasquale; Zara, Federico

2017-08-01

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and may be associated with acquired central nervous system lesions or could be genetic. Various susceptibility genes and environmental factors are believed to be involved in the aetiology of TLE, which is considered to be a heterogeneous, polygenic, and complex disorder. Rare point mutations in LGI1, DEPDC5, and RELN as well as some copy number variations (CNVs) have been reported in families with TLE patients. We perform a genetic analysis by Array-CGH in a patient with dysmorphic features and temporal lobe epilepsy. We report a de novo duplication of the long arm of chromosome 12. We confirm that 12q22-q23.3 is a candidate locus for familial temporal lobe epilepsy with febrile seizures and highlight the role of chromosomal rearrangements in patients with epilepsy and intellectual disability. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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.)

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.)

Williams Syndrome and 15q Duplication: Coincidence versus Association.

Science.gov (United States)

Khokhar, Aditi; Agarwal, Swashti; Perez-Colon, Sheila

2017-01-01

Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN -specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.

Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

Science.gov (United States)

Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

2010-09-01

We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.

Characteristic face: a key indicator for direct diagnosis of 22q11.2 deletions in Chinese velocardiofacial syndrome patients.

Science.gov (United States)

Wu, Dandan; Chen, Yang; Xu, Chen; Wang, Ke; Wang, Huijun; Zheng, Fengyun; Ma, Duan; Wang, Guomin

2013-01-01

Velocardiofacial syndrome (VCFS) is a disease in human with an expansive phenotypic spectrum and diverse genetic mechanisms mainly associated with copy number variations (CNVs) on 22q11.2 or other chromosomes. However, the correlations between CNVs and phenotypes remain ambiguous. This study aims to analyze the types and sizes of CNVs in VCFS patients, to define whether correlations exist between CNVs and clinical manifestations in Chinese VCFS patients. In total, 55 clinically suspected Chinese VCFS patients and 100 normal controls were detected by multiplex ligation-dependent probe amplification (MLPA). The data from MLPA and all the detailed clinical features of the objects were documented and analyzed. A total of 44 patients (80.0%) were diagnosed with CNVs on 22q11.2. Among them, 43 (78.2%) presented with 22q11.2 heterozygous deletions, of whom 40 (93.0%) had typical 3-Mb deletion, and 3 (7.0%) exhibited proximal 1.5-Mb deletion; no patient was found with atypical deletion on 22q11.2. One patient (1.8%) presented with a 3-Mb duplication mapping to the typical 3-Mb region on 22q11.2, while none of the chromosomal abnormalities in the MLPA kit were found in the other 11 patients and 100 normal controls. All the 43 patients with 22q11.2 deletions displayed characteristic face and palatal anomalies; 37 of them (86.0%) had cognitive or behavioral disorders, and 23 (53.5%) suffered from immune deficiencies; 10 patients (23.3%) manifested congenital heart diseases. Interestingly, all patients with the characteristic face had 22q11.2 heterozygous deletions, but no difference in phenotypic spectrum was observed between 3-Mb and 1.5-Mb deletions. Our data suggest that the characteristic face can be used as a key indicator for direct diagnosis of 22q11.2 deletions in Chinese VCFS patients.

Deletions at chromosome regions 7q11.23 and 7q36 in a patient with Williams syndrome

NARCIS (Netherlands)

Wouters, C. H.; Meijers-Heijboer, H. J.; Eussen, B. J.; van der Heide, A. A.; van Luijk, R. B.; van Drunen, E.; Beverloo, B. B.; Visscher, F.; van Hemel, J. O.

2001-01-01

We report on a patient with Williams syndrome and a complex de novo chromosome rearrangement, including microdeletions at 7q11.23 and 7q36 and additional chromosomal material at 7q36. The nature of this additional material was elucidated by spectral karyotyping and first assigned to chromosome 22.

Fine mapping of a de novo interstitial 10q22-q23 duplication in a patient with congenital heart disease and microcephaly

DEFF Research Database (Denmark)

Erdogan, F; Belloso, J M; Gabau, E

2008-01-01

deletions or duplications elsewhere in the genome. The main clinical features of the patient are microcephaly and congenital heart disease, which are likely to be caused by dosage effect of one or several genes in the duplicated region. Similar phenotypes have been found in other patients with 10q11-q22...

Neural correlates of reward processing in adults with 22q11 deletion syndrome

NARCIS (Netherlands)

van Duin, Esther D. A.; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

2016-01-01

Background: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic

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…

A case of de novo duplication of 15q24-q26.3

Directory of Open Access Journals (Sweden)

Hye Ran Kim

2011-06-01

Full Text Available Distal duplication, or trisomy 15q, is an extremely rare chromosomal disorder characterized by prenatal and postnatal overgrowth, mental retardation, and craniofacial malformations. Additional abnormalities typically include an unusually short neck, malformations of the fingers and toes, scoliosis and skeletal malformations, genital abnormalities, particularly in affected males, and, in some cases, cardiac defects. The range and severity of symptoms and physical findings may vary from case to case, depending upon the length and location of the duplicated portion of chromosome 15q. Most reported cases of duplication of the long arm of chromosome 15 frequently have more than one segmental imbalance resulting from unbalanced translocations involving chromosome 15 and deletions in another chromosome, as well as other structural chromosomal abnormalities. We report a female newborn with a de novo duplication, 15q24- q26.3, showing intrauterine overgrowth, a narrow asymmetric face with down-slanting palpebral fissures, a large, prominent nose, and micrognathia, arachnodactyly, camptodactyly, congenital heart disease, hydronephrosis, and hydroureter. Chromosomal analysis showed a 46,XX,inv(9(p12q13,dup(15(q24q26.3. Array comparative genomic hybridization analysis revealed a gain of 42 clones on 15q24-q26.3. This case represents the only reported patient with a de novo 15q24-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component in Korea.

Vitamin D deficiency, behavioral atypicality, anxiety and depression in children with chromosome 22q11.2 deletion syndrome.

Science.gov (United States)

Kelley, L; Sanders, A F P; Beaton, E A

2016-12-01

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex developmental disorder with serious medical, cognitive and emotional symptoms across the lifespan. This genetic deletion also imparts a lifetime risk for developing schizophrenia that is 25-30 times that of the general population. The origin of this risk is multifactorial and may include dysregulation of the stress response and immunological systems in relation to brain development. Vitamin D is involved in brain development and neuroprotection, gene transcription, immunological regulation and influences neuronal signal transduction. Low levels of vitamin D are associated with schizophrenia, depression and anxiety in the general population. Yet, little is known about how vitamin D levels in children with 22q11.2DS could mediate risk of psychosis in adulthood. Blood plasma levels of vitamin D were measured in children aged 7-16 years with (n=11) and without (n=16) 22q11.2DS in relation to parent reports of children's anxiety and atypicality. Anxiety and atypicality in childhood are risk indicators for the development of schizophrenia in those with 22q11.2DS and the general population. Children with 22q11.2DS had lower vitamin D levels, as well as elevated anxiety and atypicality compared with typical peers. Higher levels of anxiety, depression and internalizing problems but not atypicality were associated with lower levels of vitamin D. Vitamin D insufficiency may relate to higher levels of anxiety and depression, in turn contributing to the elevated risk of psychosis in this population. Further study is required to determine casual linkages between anxiety, stress, mood and vitamin D in children with 22q11.2DS.

The Danish 22q11 research initiative

DEFF Research Database (Denmark)

Schmock, Henriette; Vangkilde, Anders; Larsen, Kit Melissa

2015-01-01

mechanisms may come from studies of subjects with homogenous etiologies. Breakthroughs in psychiatric genetics have shown that several genetic anomalies predispose for neurodevelopmental brain disorders. We have established a Danish research initiative to study the common microdeletion at chromosome 22q11...

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 duplication...

Clinical, Cytogenetic, and Biochemical Analyses of a Family with a t(3;13(q26.2;p11.2: Further Delineation of 3q Duplication Syndrome

Directory of Open Access Journals (Sweden)

M. Abreu-González

2013-01-01

Full Text Available Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%–75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13(q26.2;p11.2. As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype.

Social cognitive training in adolescents with chromosome 22q11.2 deletion syndrome: feasibility and preliminary effects of the intervention.

Science.gov (United States)

Shashi, V; Harrell, W; Eack, S; Sanders, C; McConkie-Rosell, A; Keshavan, M S; Bonner, M J; Schoch, K; Hooper, S R

2015-10-01

Children with chromosome 22q11.2 deletion syndrome (22q11DS) often have deficits in social cognition and social skills that contribute to poor adaptive functioning. These deficits may be of relevance to the later occurrence of serious psychiatric illnesses such as schizophrenia. Yet, there are no evidence-based interventions to improve social cognitive functioning in children with 22q11DS. Using a customised social cognitive curriculum, we conducted a pilot small-group-based social cognitive training (SCT) programme in 13 adolescents with 22q11DS, relative to a control group of nine age- and gender-matched adolescents with 22q11DS. We found the SCT programme to be feasible, with high rates of compliance and satisfaction on the part of the participants and their families. Our preliminary analyses indicated that the intervention group showed significant improvements in an overall social cognitive composite index. SCT in a small-group format for adolescents with 22q11DS is feasible and results in gains in social cognition. A larger randomised controlled trial would permit assessment of efficacy of this promising novel intervention. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

A cross-sectional analysis of the development of response inhibition in children with Chromosome 22q11.2 Deletion Syndrome

Directory of Open Access Journals (Sweden)

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.

A 15 Mb large paracentric chromosome 21 inversion identified in Czech population through a pair of flanking duplications.

Science.gov (United States)

Drabova, Jana; Trkova, Marie; Hancarova, Miroslava; Novotna, Drahuse; Hejtmankova, Michaela; Havlovicova, Marketa; Sedlacek, Zdenek

2014-01-01

Inversions are balanced structural chromosome rearrangements, which can influence gene expression and the risk of unbalanced chromosome constitution in offspring. Many examples of inversion polymorphisms exist in human, affecting both heterochromatic regions and euchromatin. We describe a novel, 15 Mb long paracentric inversion, inv(21)(q21.1q22.11), affecting more than a third of human 21q. Despite of its length, the inversion cannot be detected using karyotyping due to similar band patterns on the normal and inverted chromosomes, and is therefore likely to escape attention. Its identification was aided by the repeated observation of the same pair of 150 kb long duplications present in cis on chromosome 21 in three Czech families subjected to microarray analysis. The finding prompted us to hypothesise that this co-occurrence of two remote duplications could be associated with an inversion of the intervening segment, and this speculation turned out to be right. The inversion was confirmed in a series of FISH experiments which also showed that the second copy of each of the duplications was always located at the opposite end of the inversion. The presence of the same pair of duplications in additional individuals reported in public databases indicates that the inversion may also be present in other populations. Three out of the total of about 4000 chromosomes 21 examined in our sample carried the duplications and were inverted, corresponding to carrier frequency of about 1/660. Although the breakpoints affect protein-coding genes, the occurrence of the inversion in normal parents and siblings of our patients and the occurrence of the duplications in unaffected controls in databases indicate that this rare variant is rather non-pathogenic. The inverted segment carried an identical shared haplotype in the three families studied. The haplotypes, however, diverged very rapidly in the flanking regions, possibly pointing to an ancient founder event at the origin of the

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.

A chromosome 10 variant with a 12 Mb inversion [inv(10)(q11.22q21.1)] identical by descent and frequent in the Swedish population.

Science.gov (United States)

Entesarian, Miriam; Carlsson, Birgit; Mansouri, Mahmoud Reza; Stattin, Eva-Lena; Holmberg, Eva; Golovleva, Irina; Stefansson, Hreinn; Klar, Joakim; Dahl, Niklas

2009-03-01

We identified a paracentric inversion of chromosome 10 [inv(10)(q11.22q21.1)] in 0.20% of Swedish individuals (15/7,439) referred for cytogenetic analysis. A retrospective analysis of 8,896 karyotypes from amniocenteses in Sweden revealed a carrier frequency of 0.079% (7/8,896) for the inversion. Cloning and detailed analysis of the inversion breakpoint regions show enrichment for interspersed repeat elements and AT-stretches. The centromeric breakpoint coincides with that of a predicted inversion from HapMap data, which suggests that this region is involved in several chromosome 10 variants. No known gene or predicted transcript are disrupted by the inversion which spans approximately 12 Mb. Carriers from four non-related Swedish families have identical inversion breakpoints and haplotype analysis confirmed that the rearrangement is identical by descent. Diagnosis was retrieved in 6 out of the 15 carriers referred for cytogenetic analysis. No consistent phenotype was found to be associated with the inversion. Our study demonstrates that the inv(10)(q11.22q21.1) is a rare and inherited chromosome variant with a broad geographical distribution in Sweden. 2009 Wiley-Liss, Inc.

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.

Noonan's and DiGeorge syndromes with monosomy 22q11.

OpenAIRE

Wilson, D I; Britton, S B; McKeown, C; Kelly, D; Cross, I E; Strobel, S; Scambler, P J

1993-01-01

A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome.

A 54 Mb 11qter duplication and 0.9 Mb 1q44 deletion in a child with laryngomalacia and agenesis of corpus callosum

Directory of Open Access Journals (Sweden)

Lall Meena

2011-09-01

Full Text Available Abstract Background Partial Trisomy 11q syndrome (or Duplication 11q has defined clinical features and is documented as a rare syndrome by National Organization of Rare Disorders (NORD. Deletion 1q44 (or Monosomy 1q44 is a well-defined syndrome, but there is controversy about the genes lying in 1q44 region, responsible for agenesis of the corpus callosum. We report a female child with the rare Partial Trisomy 11q syndrome and Deletion 1q44 syndrome. The genomic imbalance in the proband was used for molecular characterization of the critical genes in 1q44 region for agenesis of corpus callosum. Some genes in 11q14q25 may be responsible for laryngomalacia. Results We report a female child with dysmorphic features, microcephaly, growth retardation, seizures, acyanotic heart disease, and hand and foot deformities. She had agenesis of corpus callosum, laryngomalacia, anterior ectopic anus, esophageal reflux and respiratory distress. Chromosome analysis revealed a derivative chromosome 1. Her karyotype was 46,XX,der(1t(1;11(q44;q14pat. The mother had a normal karyotype and the karyotype of the father was 46,XY,t(1;11(q44;q14. SNP array analysis showed that the proband had a 54 Mb duplication of 11q14q25 and a 0.9 Mb deletion of the submicroscopic subtelomeric 1q44 region. Fluorescence Insitu Hybridisation confirmed the duplication of 11qter and deletion of 1qter. Conclusion Laryngomalacia or obstruction of the upper airway is the outcome of increased dosage of some genes due to Partial Trisomy 11q Syndrome. In association with other phenotypic features, agenesis of corpus callosum appears to be a landmark phenotype for Deletion 1q44 syndrome, the critical genes lying proximal to SMYD3 in 1q44 region.

Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21

DEFF Research Database (Denmark)

McGinniss, M J; Kazazian, H H; Stetten, G

1992-01-01

We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6 with de novo r(21). The copy number of chromosome 21 sequences in the rings of these patients was determined by quantitative dosage......), resulting in deletion of varying amounts of 21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype were consistent with asymmetric breakage and reunion of 21q sequences from an intermediate isochromosome or Robertsonian translocation chromosome as reported by Wong et al. Another......). The phenotype of patients correlated well with the extent of deletion or duplication of chromosome 21 sequences. These data demonstrate three mechanisms of r(21) formation and show that the phenotype of r(21) patients varies with the extent of chromosome 21 monosomy or trisomy....

Mosaicism for r(X and der(Xdel(X(p11.23dup(X(p11.21p11.22 provides insight into the possible mechanism of rearrangement

Directory of Open Access Journals (Sweden)

Fang Ping

2008-07-01

Full Text Available Abstract We report a patient with a unique and complex cytogenetic abnormality involving mosaicism for a small ring X and deleted Xp derivative chromosome with tandem duplication at the break point. The patient presented with failure to thrive, muscular hypotonia, and minor facial anatomic anomalies, all concerning for Turner syndrome. Brain MRI revealed mild thinning of the corpus callosum, an apparent decrease in ventricular white matter volume, and an asymmetric myelination pattern. Array comparative genome hybridization analysis revealed mosaicism for the X chromosome, deletion of the short arm of an X chromosome, and a duplication of chromosome region Xp11.21-p11.22. G-banded chromosome and FISH analyses revealed three abnormal cell lines: 46,X,der(Xdel(X(p11.23dup(X(p11.21p11.22/46,X,r(X(q11.1q13.1/45,X. The small ring X chromosome was estimated to be 5.2 Mb in size and encompassed the centromere and Xq pericentromeric region. X chromosome inactivation (XCI studies demonstrated a skewed pattern suggesting that the ring X remained active, likely contributing to the observed clinical features of brain dysmyelination. We hypothesize that a prezygotic asymmetric crossing over within a loop formed during meiosis in an X chromosome with a paracentric inversion resulted in an intermediate dicentric chromosome. An uneven breakage of the dicentric chromosome in the early postzygotic period might have resulted in the formation of one cell line with the X chromosome carrying a terminal deletion and pericentromeric duplication of the short arm and the second cell line with the X chromosome carrying a complete deletion of Xp. The cell line carrying the deletion of Xp could have then stabilized through self-circularization and formation of the ring X chromosome.

Exclusion of 22q11 deletion in Noonan syndrome with Tetralogy of Fallot

Energy Technology Data Exchange (ETDEWEB)

Digilio, M.C.; Marino, B.; Giannotti, A. [Bambino Gesu Hospital, Rome (Italy); Dallapiccola, B. [Univ. of Tor Vergata, Rome (Italy)]|[Casa Sollievo Sofferenza Hospital, San Giovanni Rotondo (Italy)

1996-04-24

We read with interest the report of Robin et al. [1995] published in recent issue of the Journal. The authors described 6 patients with Noonan syndrome (NS) who underwent molecular evaluation for submicroscopic deletion of chromosome band 22q11. None of those patients presented with conotruncal heart defects. Evidence for 22q11 hemizygosity was demonstrated in only one patient. This patient had NS-like manifestations without clinical manifestations of DiGeorge (DG) or velo-cardio-facial (VCF) syndromes. The molecular results obtained in the other 5 patients led the authors to conclude that classical NS is not due to del(22)(q11), even if some patients with del(22)(q11) may present NS-like manifestations. 12 refs., 1 tab.

Recurrent duplications of 17q12 associated with variable phenotypes

DEFF Research Database (Denmark)

Mitchell, Elyse; Douglas, Andrew; Kjaegaard, Susanne

2015-01-01

The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information......, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing...... to phenotypic variability....

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…

[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.

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 m...

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…

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

OpenAIRE

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...

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

Chromosome 10q tetrasomy: First reported case

Energy Technology Data Exchange (ETDEWEB)

Blackston, R.D.; May, K.M.; Jones, F.D. [Emory Univ., Atlanta, GA (United States)] [and others

1994-09-01

While there are several reports of trisomy 10q (at least 35), we are not aware of previous cases of 10q tetrasomy. We present what we believe to be the initial report of such a case. R.J. is a 6 1/2 year old white male who presented with multiple dysmorphic features, marked articulation problems, hyperactivity, and developmental delays. He is the product of a term uncomplicated pregnancy. There was a normal spontaneous vaginal delivery with a birth weight of 6 lbs. 4oz. and length was 19 1/2 inch. Dysmorphic features include small size, an asymmetrically small head, low set ears with overfolded helixes, bilateral ptosis, downslanting eyes, right eye esotropia, prominent nose, asymmetric facies, high palate, mild pectus excavatum deformity of chest, and hyperextensible elbow joints. The patient is in special needs classes for mildly mentally handicapped students. Chromosome analysis at a resolution of 800 bands revealed a complex rearrangement of chromosomes 10 and 11. The segment 10q25.3 to q16.3 appears to be inverted and duplicated within the long arm of chromosome 10 at band q25.3 and the same segment of chromosome 10 is present on the terminal end of the short arm of chromosome 11. There is no visible loss of material from chromosome 11. Fluorescence in situ hybridization was performed with a chromosome 10 specific {open_quotes}paint{close_quotes} to confirm that all of the material on the abnormal 10 and the material on the terminal short arm of 11 was from chromosome 10. Thus, it appears that the segment 10q25.3 to q26.3 is present in four copies. Parental chromosome studies are normal. We compared findings which differ in that the case of 10q tetrasomy did not have prenatal growth deficiency, microphthalmia, cleft palate, digital anomalies, heart, or renal defects. Whereas most cases of 10q trisomy are said to have severe mental deficiency, our case of 10q tetrasomy was only mildly delayed. We report this first apparent cited case of 10q tetrasomy.

Neural correlates of reward processing in adults with 22q11 deletion syndrome.

Science.gov (United States)

van Duin, Esther D A; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

2016-01-01

22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS

Rare genome-wide copy number variation and expression of schizophrenia in 22q11.2 deletion syndrome

NARCIS (Netherlands)

Bassett, Anne S.; Lowther, Chelsea; Merico, Daniele; Costain, Gregory; Chow, Eva W C; Van Amelsvoort, Therese; McDonald-Mcginn, Donna M.; Gur, Raquel E.; Swillen, Ann; van den Bree, Marianne B M; Murphy, Kieran C.; Gothelf, Doron; Bearden, Carrie E.; Eliez, Stephan; Kates, Wendy R.; Philip, Nicole; Sashi, Vandana; Campbell, Linda E.; Vorstman, Jacob; Cubells, Joseph; Repetto, Gabriela M.; Simon, Tony J.; Boot, Erik; Heung, Tracy; Evers, Rens; Vingerhoets, Claudia; Van Duin, Esther; Zackai, Elaine; Vergaelen, Elfi; Devriendt, Koen; Vermeesch, Joris R.; Owen, Michael J; Murphy, Clodagh M.; Michaelovosky, Elena; Kushan, Leila; Schneider, Maude; Fremont, Wanda; Busa, Tiffany; Hooper, Stephen R.; 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.

2017-01-01

Objective: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this studywas to identify additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression. Method: Through an

New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22(q34;p11;q11

Directory of Open Access Journals (Sweden)

Abdeljabar El Andaloussi

2007-01-01

Full Text Available A Chronic myeloid leukaemia (CML case with a new complex t(9;18;22(q34;p11;q11 of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH. In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importance of combined cytogenetic analysis for diagnosis and guidance of treatment in clinical diagnosis of CML.

Chronic myeloid leukemia with variation of translocation at (Ph) [ins (22;9) (q11;q21q34)]: a case report.

Science.gov (United States)

Wang, Zhiqiong; Zen, Wen; Meng, Fankai; Xin, Xing; Luo, Li; Sun, Hanying; Zhou, Jianfeng; Huang, Lifang

2015-01-01

Chronic myeloid leukemia (CML) is most frequently observed in middle-aged individuals. In most patients, normal marrow cells are replaced by cells with an abnormal G-group chromosome, the Philadelphia (Ph) chromosome. The Ph chromosome that is characterized by the translocation (9;22) (q34;q11) is noted in 90-95% of patients diagnosed with CML. Studies have also shown that CML can be associated with various other cytogenetic abnormalities, with 5-10% of these cases showing complex translocation involving another chromosome in addition to the Ph chromosome. Here, we report the case of a Ph(+) CML patient with an inserted karyotype who presented clinically in the chronic phase but with atypical features. This case highlights the significance of cytogenetic abnormalities on the prognosis in CML.

NEUROD2 and NEUROD3 genes map to human chromosomes 17q12 and 5q23-q31 and mouse chromosomes 11 and 13, respectively

Energy Technology Data Exchange (ETDEWEB)

Tamimi, R.M.; Montgomery-Dyer, K.; Tapscott, S.J. [Fred Hutchinson Cancer Research Center, Seattle, WA (United States)] [and others

1997-03-01

NEUROD2 and NEUROD3 are transcription factors involved in neurogenesis that are related to the basic helix-loop-helix protein NEUROD. NEUROD2 maps to human chromosome 17q12 and mouse chromosome 11. NEUROD3 maps to human chromosome 5q23-q31 and mouse chromosome 13. 16 refs., 2 figs.

6q16.3q23.3 duplication associated with Prader-Willi-like syndrome.

Science.gov (United States)

Desch, Laurent; Marle, Nathalie; Mosca-Boidron, Anne-Laure; Faivre, Laurence; Eliade, Marie; Payet, Muriel; Ragon, Clemence; Thevenon, Julien; Aral, Bernard; Ragot, Sylviane; Ardalan, Azarnouche; Dhouibi, Nabila; Bensignor, Candace; Thauvin-Robinet, Christel; El Chehadeh, Salima; Callier, Patrick

2015-01-01

Prader-Willi syndrome (PWS) is characterized by hypotonia, delayed neuropsychomotor development, overeating, obesity and mental deficiency. This phenotype is encountered in other conditions, defining Prader-Willi-like syndrome (PWLS). We report a 14-year-old boy with a complex small supernumerary marker chromosome (sSMC) associated with PWLS. The propositus presents clinical features commonly found in patients with PWLS, including growth hormone deficit. Banding karyotype analysis and fluorescence in situ hybridization (FISH) revealed a marker derived from chromosome 6 and a neocentromere as suspected, but array-CGH enabled us to characterize this marker as a der(10)t(6;10)(6qter → 6q23.3::10p11.1 → 10p11.21)dn. As far as we know, this is the first diagnosed case of PWLS associated with a complex sSMC, involving a 30.9 Mb gain in the 6q16.3q23.3 region and a 3.5 Mb gain in the 10p11.21p11.1 region. Several genes have been mapped to the 6q region including the TCBA1 gene, which is associated with developmental delay and recurrent infections, the ENPP1 gene, associated with insulin resistance and susceptibility to obesity and the BMIQ3 gene, associated with body mass index (BMI). No OMIM gene was found in the smallest 10p11.21p11.1 region. We suggest that the duplicated chromosome segment 6q16.3q23.3 may be responsible for the phenotype of our case and may also be a candidate locus of PWLS.

Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma

International Nuclear Information System (INIS)

Rao, Pulivarthi H; Murty, Vundavalli VVS; Arias-Pulido, Hugo; Lu, Xin-Yan; Harris, Charles P; Vargas, Hernan; Zhang, Fang F; Narayan, Gopeshwar; Schneider, Achim; Terry, Mary Beth

2004-01-01

Carcinoma of uterine cervix is the second most common cancers among women worldwide. Combined radiation and chemotherapy is the choice of treatment for advanced stages of the disease. The prognosis is poor, with a five-year survival rate ranging from about 20–65%, depending on stage of the disease. Therefore, genetic characterization is essential for understanding the biology and clinical heterogeneity in cervical cancer (CC). We used a genome-wide screening method – comparative genomic hybridization (CGH) to identify DNA copy number changes in 77 patients with cervical cancer. We applied categorical and survival analyses to analyze whether chromosomal changes were related to clinico-pathologic characteristics and patients survival. The CGH analysis revealed a loss of 2q33-q37 (57.1%), gain of 3q (54.5%) and chromosomal amplifications (20.77%) as frequent genetic changes. A total of 15 amplified chromosomal sites were detected in 16 cases that include 1p31, 2q32, 7q22, 8q21.2-q24, 9p22, 10q21, 10q24, 11q13, 11q21, 12q15, 14q12, 17p11.2, 17q22, 18p11.2, and 19q13.1. Recurrent amplified sites were noted at 11q13, 11q21, and 19q13.1. The genomic alterations were further evaluated for prognostic significance in CC patients, and we did not find any correlation with a number of clinical or histological parameters. The tumors harboring HPV18 exhibited higher genomic instability compared to tumors with HPV 16. This study demonstrated that 2q33-q37 deletions, 3q gains and chromosomal amplifications as characteristic changes in invasive CC. These genetic alterations will aid in the identification of novel tumor suppressor gene(s) at 2q33-q37 and oncogenes at amplified chromosomal sites. Molecular characterization of these chromosomal changes utilizing the current genomic technologies will provide new insights into the biology and clinical behavior of CC

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.

Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome.

Directory of Open Access Journals (Sweden)

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.

Tetrasomy 15q11-q13 Diagnosed by FISH in a Patient with Autistic Disorder

Directory of Open Access Journals (Sweden)

Karim Ouldim

2007-01-01

Full Text Available We report the case of a Moroccan boy with mental retardation, hyperactivity, epilepsy, developmental problems and behavioural disorders. Cytogenetic analysis showed the presence of a supernumerary marker chromosome. Molecular cytogenetics allowed us to determine the marker as an inverted duplication of chromosome 15. It is the first case of a Moroccan patient with tetrasomy 15q in which fluorescence in situ hybridization (FISH enabled us to specify the diagnosis. Interestingly, this patient has an infantile autism with cytogenetic abnormalities on chromosomal region 15q11-q13 as reported in patients with Autistic Disorder.

Construction of a DNA library representing 15q11-13 by subtraction of two flow sorted marker chromosome-specific libraries

Energy Technology Data Exchange (ETDEWEB)

Blennow, E.; Werelius, B.; Nordenskjoeld, M. [Karolinska Hospital, Stockholm (Sweden)] [and others

1994-09-01

Constitutional extra {open_quotes}marker chromosomes{close_quotes} are found in {approx}0.5/1000 of newborns. Of these, 50% are inverted duplications of the pericentromeric region of chromosome 15, including two variants; (1) inv dup(15)(pter{yields}q11:q11{yields}pter) and (2) inv dup(15) (pter{yields}q12-13::q12-13{yields}pter). Variant (1) is found in phenotypically normal individuals, whereas variant (2) will produce a typical clinical picture including mental retardation, autism, hyperactivity and discrete dysmorphic features. Fluorescence in situ hybridization (FISH) using single copy probes from the Prader-Willi region confirms these observations as well as chromosome painting using a flow-sorted marker chromosome-specific library from a variant (1) marker, hybridized to the chromosomes of a patient with a variant (2) marker chromosome. Followingly, a flow-sorted biotinylated variant (1) library was subtracted from a non-labeled variant (2) library using magnetic beads and subsequent amplification by degenerate oligonucleotide-primed PCR (DOP-PCR). The successful result was demonstrated by using the amplified material for chromosome painting on chromosome slides from variant (1) and variant (2) patients. We have constructed a library from 15q11-13. This region contains genes producing a specific abnormal phenotype when found in a tri- or tetrasomic state. The region also contains the genes responsible for the Prader-Willi and Angelman syndromes when the paternal/maternal copy is missing, respectively. It is therefore a region where parental imprinting plays an important role. The isolated library may be used to isolate single copy clones which will allow further investigations of this region.

Two sequence-ready contigs spanning the two copies of a 200-kb duplication on human 21q: partial sequence and polymorphisms.

Science.gov (United States)

Potier, M; Dutriaux, A; Orti, R; Groet, J; Gibelin, N; Karadima, G; Lutfalla, G; Lynn, A; Van Broeckhoven, C; Chakravarti, A; Petersen, M; Nizetic, D; Delabar, J; Rossier, J

1998-08-01

Physical mapping across a duplication can be a tour de force if the region is larger than the size of a bacterial clone. This was the case of the 170- to 275-kb duplication present on the long arm of chromosome 21 in normal human at 21q11.1 (proximal region) and at 21q22.1 (distal region), which we described previously. We have constructed sequence-ready contigs of the two copies of the duplication of which all the clones are genuine representatives of one copy or the other. This required the identification of four duplicon polymorphisms that are copy-specific and nonallelic variations in the sequence of the STSs. Thirteen STSs were mapped inside the duplicated region and 5 outside but close to the boundaries. Among these STSs 10 were end clones from YACs, PACs, or cosmids, and the average interval between two markers in the duplicated region was 16 kb. Eight PACs and cosmids showing minimal overlaps were selected in both copies of the duplication. Comparative sequence analysis along the duplication showed three single-basepair changes between the two copies over 659 bp sequenced (4 STSs), suggesting that the duplication is recent (less than 4 mya). Two CpG islands were located in the duplication, but no genes were identified after a 36-kb cosmid from the proximal copy of the duplication was sequenced. The homology of this chromosome 21 duplicated region with the pericentromeric regions of chromosomes 13, 2, and 18 suggests that the mechanism involved is probably similar to pericentromeric-directed mechanisms described in interchromosomal duplications. Copyright 1998 Academic Press.

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…

Simultaneous occurrence of t(9;22)(q34;q11.2) and t(16;16)(p13;q22) in a patient with chronic myeloid leukemia in blastic phase.

Science.gov (United States)

Zámecníkova, Adriana; Al Bahar, Soad; Ramesh, Pandita

2008-06-01

Coexistence of two specific chromosomal translocations in the same clone is an infrequent phenomenon and has only rarely been reported in hematological malignancies. We report a combination of t(16;16)(p13;q22), the Philadelphia translocation t(9;22)(q34;q11.2), and deletion of the long arm of chromosome 7 in a patient with chronic myeloid leukemia in blast phase. Monotherapy treatment with imatinib mesylate resulted in the disappearance of the Ph-positive clone, but with persistence of t(16;16) and del(7) in all of the metaphases examined. The case illustrates that, although imatinib mesylate can be an effective treatment in eradication of the BCR-ABL fusion gene cells, the occurrence of additional specific abnormalities in Philadelphia-positive leukemias may pose a significant therapeutic challenge. (c) 2008 Elsevier Inc.

Seizures as the first manifestation of chromosome 22q11.2 deletion syndrome in a 40-year old man: a case report

Directory of Open Access Journals (Sweden)

Tonelli Adriano R

2007-12-01

Full Text Available Abstract Background The microdeletion of chromosome 22q11.2 is the most common human deletion syndrome. It typically presents early in life and is rarely considered in adult patients. As part of the manifestations of this condition, patients can have parathyroid glandular involvement ranging from hypocalcemic hypoparathyroidism to normocalcemia with normal parathryroid hormone levels. The first manifestation of the syndrome might be seizures due to profound hypocalcemia. Case presentation A 40-year-old man without significant past medical history presented with a new-onset generalized tonic-clonic seizure. He had no personal history of hypocalcemia or seizures. Physical examination was remarkable for short stature, hypertelorism, prominent forehead and nasal voice. His initial laboratory examination showed hypocalcemia (Calcium 5.2 mg/dl and Calcium ionized 0.69 mmol/l with hypoparathyroidism (Parathyroid hormone intact Conclusion Microdeletion of chromosome 22q11.2 is among the most clinically variable syndromes, with more than 180 features associated with the deletion. It has a variable phenotypical expression, requiring a high level of awareness for its early diagnosis. Seizures, related to marked hypocalcemia due to idiopathic hypoparathyroidism, might be the presenting feature in an adult patient with this syndrome.

Inactivation of the P16INK4/MTS1 gene by a chromosome translocation t(9;14)(p21-22;q11) in an acute lymphoblastic leukemia of B-cell type.

Science.gov (United States)

Duro, D; Bernard, O; Della Valle, V; Leblanc, T; Berger, R; Larsen, C J

1996-02-15

We have reported previously a preliminary study of a t(9;14)(p21-22; q11) in B-cell acute lymphoblastic leukemia. This translocation had rearranged the TCRA/D locus on chromosome band 14q11 and the locus encoding the tumor suppressor gene P16INK4/MTS1 (P16) on band 9p21 (D. Duro et al., Oncogene, 11: 21-29, 1995). In the present report, the breakpoints were precisely localized on each chromosome partner. On the 14q- derivative, the sequence derived from chromosome 9 was interrupted at 1.0 kb upstream of the first exon of P16, close to a consensus recombination heptamer, CACTGTG. In addition, the chromosome 14 breakpoint was localized at the end of the TCRD2 (delta 2) segment, and 22 residues with unknown origin were present at the translocation junction. On the 9p+ derivative, chromosome 9 sequences were in continuity with those displaced onto chromosome 14, and the 14q11 breakpoint was located within TCRJA29 segment. These features are consistent with aberrant activity of the TCR gene recombinase complex. Although all three coding exons of P16 were displaced onto the chromosome 14q-derivative, no P16 transcript was detected in the leukemic cells. Because the region spanning the P16 exon 1 was not inactivated by methylation and because the other P16 allele was deleted, the implication is that the chromosome breakpoint was likely to disrupt regulatory elements involved in the normal expression of the gene. As a whole, then, our results show that translocations affecting band 9p21 can participate to the inactivation of P16, thus justifying a systematic survey of translocations of the 9p21 band in acute lymphoblastic leukemia.

A familial pericentric inversion of chromosome 11 associated with a microdeletion of 163 kb and microduplication of 288 kb at 11p13 and 11q22.3 without aniridia or eye anomalies.

Science.gov (United States)

Balay, Lara; Totten, Ellen; Okada, Luna; Zell, Sidney; Ticho, Benjamin; Israel, Jeannette; Kogan, Jillene

2016-01-01

Interstitial deletions of 11p13 involving MPPED2, DCDC5, DCDC1, DNAJC24, IMMP1L, and ELP4 are previously reported to have downstream transcriptional effects on the expression of PAX6, due to a downstream regulatory region (DRR). Currently, no clear genotype-phenotype correlations have been established allowing for conclusive information regarding the exact location of the PAX6 DRR, though its location has been approximated in mouse models to be within the Elp4 gene. Of the clinical reports currently published examining patients with intact PAX6 genes but harboring deletions identified in genes downstream of PAX6, 100% indicate phenotypes which include aniridia, whereas approximately half report additional eye deformities, autism, or intellectual disability. In this clinical report, we present a 12-year-old male patient, his brother, and mother with pericentric inversions of chromosome 11 associated with submicroscopic interstitial deletions of 11p13 and duplications of 11q22.3. The inversions were identified by standard cytogenetic analysis; microarray and FISH detected the chromosomal imbalance. The patient's phenotype includes intellectual disability, speech abnormalities, and autistic behaviors, but interestingly neither the patient, his brother, nor mother have aniridia or other eye anomalies. To the best of our knowledge, these findings in three family members represent the only reported cases with 11p13 deletions downstream of PAX6 not demonstrating phenotypic characteristics of aniridia or abnormal eye development. Although none of the deleted genes are obvious candidates for the patient's phenotype, the absence of aniridia in the presence of this deletion in all three family members further delineates the location of the DRR for PAX6. © 2015 Wiley Periodicals, Inc.

Heterogeneity of chromosome 22 breakpoint in Philadelphia-positive (Ph+) acute lymphocytic leukemia

International Nuclear Information System (INIS)

Erikson, J.; Griffin, C.A.; Ar-Rushdi, A.

1986-01-01

In chronic myelogenous leukemias (CML) with the t(9;22)(q34;q11) chromosome translocation the breakpoints on chromosome 22 occur within a 5.8-kilobase segment of DNA referred to as breakpoint cluster region (bcr). The same cytogenetically indinstinguishable translocation occurs in approximately 10% of patients with acute lymphocytic leukemias (ALL). In this study the authors have investigated the chromosome breakpoints in several cases of ALL carrying the t(9;22) translocation. In three of five cases of ALL they found that the bcr region was not involved in the chromosome rearrangement and that the 22q11 chromosome breakpoints were proximal (5') to the bcr region at band 22q11. In addition, they observed normal size bcr and c-alb transcripts in an ALL cell line carrying the t(9;22) translocation. They conclude, therefore, that if c-alb is inappropriately expressed in ALL cells without bcr rearrangements, the genetic mechanism of activation must be different from that reported for CML

Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

Directory of Open Access Journals (Sweden)

Qiong Pan

Full Text Available Complex chromosome rearrangements (CCRs, which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques.

Brief Report: Visual-Spatial Deficit in a 16-Year-Old Girl with Maternally Derived Duplication of Proximal 15q

Science.gov (United States)

Cohen, David; Martel, Claire; Wilson, Anna; Dechambre, Nicole; Amy, Celine; Duverger, Ludovic; Guile, Jean-Marc; Pipiras, Eva; Benzacken, Brigitte; Cave, Helene; Cohen, Laurent; Heron, Delphine; Plaza, Monique

2007-01-01

Duplications of chromosome 15 may be one of the most common single genetic causes of autism spectrum disorders (ASD), aside from fragile X. Most of the cases are associated with maternally derived interstitial duplication involving 15q11-13. This case report describes a female proband with a maternally derived interstitial duplication of proximal…

Velo-Cardio-Facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region

Energy Technology Data Exchange (ETDEWEB)

Nickel, R.E.; Pillers, D.M.; Merkens, M.; Magenis, R.E.; Zonana, J. [Oregon Health Sciences Univ., Portland, OR (United States); Driscoll, D.A.; Emanuel, B.S. [Univ. of Pennsylvania Medical Center, Philadelphia, PA (United States)

1994-10-01

Approximately 5% of children with neural tube defects (NTDs) have a congenital heart defect and/or cleft lip and palate. The cause of isolated meningomyelocele, congenital heart defects, or cleft lip and palate has been largely thought to be multifactorial. However, chromosomal, teratogenic, and single gene causes of combinations of NTDs with congenital heart defects and/or cleft lip and palate have been reported. We report on 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of velo-cardio-facial syndrome (VCFS); both have bifid uvula. The third child had DiGeorge sequence (DGS). The association of NTDs with 22q11 deletion has not been reported previously. An accurate diagnosis of the 22q11 deletion is critical as this micro-deletion and its associated clinical problems is transmitted as an autosomal dominant trait due to the inheritance of the deletion-bearing chromosome. We recommend that all children with NTDs and congenital heart defects, with or without cleft palate, have cytogenetic and molecular studies performed to detect 22q11 deletions. 31 refs., 3 figs.

Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2

Energy Technology Data Exchange (ETDEWEB)

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.

A Quantitative Electrophysiological Biomarker of Duplication 15q11.2-q13.1 Syndrome.

Directory of Open Access Journals (Sweden)

Joel Frohlich

Full Text Available Duplications of 15q11.2-q13.1 (Dup15q syndrome are highly penetrant for autism spectrum disorder (ASD. A distinct electrophysiological (EEG pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome.In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11, age-and-IQ-matched children with ASD (n = 10 and age-matched typically developing (TD children (n = 9 and computed relative power in 6 frequency bands for 9 regions of interest (ROIs. Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27 across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions.In the first study, spontaneous beta1 (12-20 Hz and beta2 (20-30 Hz power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1-4 Hz was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1. In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome.Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.

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.

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

Seizures as the first manifestation of chromosome 22q11.2 deletion syndrome in a 40-year old man: a case report

OpenAIRE

Tonelli, Adriano R; Kosuri, Kalyan; Wei, Sainan; Chick, Davoren

2007-01-01

Abstract Background The microdeletion of chromosome 22q11.2 is the most common human deletion syndrome. It typically presents early in life and is rarely considered in adult patients. As part of the manifestations of this condition, patients can have parathyroid glandular involvement ranging from hypocalcemic hypoparathyroidism to normocalcemia with normal parathryroid hormone levels. The first manifestation of the syndrome might be seizures due to profound hypocalcemia. Case presentation A 4...

Mapping of four distinct BCR-related loci to chromosome region 22q11: order of BCR loci relative to chronic myelogenous leukemia and acute lymphoblastic leukemia breakpoints

International Nuclear Information System (INIS)

Croce, C.M.; Huebner, K.; Isobe, M.; Fainstain, E.; Lifshitz, B.; Shtivelman, E.; Canaani, E.

1987-01-01

A probe derived from the 3' region of the BCR gene (breakpoint cluster region gene) detects four distinct loci in the human genome. One of the loci corresponds to the complete BCR gene, whereas the other contain a 3' segment of the gene. After HindIII cleavage of human DNA, these four loci are detected as 23-, 19-, 13-, and 9-kikobase-pair fragments, designated BCR4, BCR3, BCR2, and BCR1, respectively, with BCR1 deriving from the original complete BCR gene. All four BCR loci segregate 100% concordantly with human chromosome 22 in a rodent-human somatic cell hybrid panel and are located at chromosome region 22q11.2 by chromosomal in situ hybridization. The BCR2 and BCR4 loci are amplified in leukemia cell line K562 cells, indicating that they fall within the amplification unit that includes immunoglobulin λ light chain locus (IGL) and ABL locus on the K562 Philadelphia chromosome (Ph 1 ). Similarly, in mouse-human hybrids retaining a Ph 1 chromosome derived from an acute lymphoblastic leukemia-in the absence of the 9q + and 22, only BCR2 and BCR4 loci are retained. Thus, the order of loci on chromosome 22 is centromere → BCR2, BCR4, and IGL → BCR1 → BCR3 → SIS, possibly eliminating BCR2 and BCR4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph 1 chromosome

Identifying patterns of anxiety and depression in children with chromosome 22q11.2 deletion syndrome: comorbidity predicts behavioral difficulties and impaired functional communications.

Science.gov (United States)

Stephenson, David D; Beaton, Elliott A; Weems, Carl F; Angkustsiri, Kathleen; Simon, Tony J

2015-01-01

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex genetic disorder with a variable clinical presentation that can include cardiac, neural, immunological, and psychological issues. Previous studies have measured elevated anxiety and depression in children with 22q11.2DS. Comorbity of anxiety and depression is well established in the pediatric literature but the nature of comorbidity patterns has not been empirically established in children with 22q11.2DS. Comorbidity of anxiety and depression has important implications for treatment and prognosis, and may be a marker of risk in this population of children at high-risk for developing schizophrenia. Participants were 131 boys and girls ages 8-14 with (n=76) and without (n=55) 22q11.2DS and their mothers. Children and mothers independently completed self- and parent-report measures of anxiety and depression. Mothers also completed measures of behavioral functioning including the Behavioral Assessment for Children, 2nd ed. (BASC-2). Cluster analyses were conducted to test if theoretically based groupings of anxiety and depression could be identified. We hypothesized four psychological profiles based on child- and mother-reports: low/no anxiety and low/no depression, higher depression and low/no anxiety, higher anxiety and no/low depression, and a comorbid profile of higher anxiety and higher depression. BASC-2 subscale scores were then compared across subgroups of children to determine if a comorbid profile would predict greater behavioral difficulties. In the full sample of children both with and without 22q11.2DS, cluster analyses of self and maternal reported anxiety and depression revealed the expected subgroups: (1) a group of children with higher anxiety/lower depression (anxious); (2) a group with primary depression (lower anxiety/higher depression (depressed)); (3) a comorbid group with higher anxiety/higher depression (comorbid); and, (4) a lowest anxiety/lowest depression group (NP). Mothers

Mirror-symmetric duplicated chromosome 21q with minor proximal deletion, and with neocentromere in a child without the classical Down syndrome phenotype.

Science.gov (United States)

Barbi, G; Kennerknecht, I; Wöhr, G; Avramopoulos, D; Karadima, G; Petersen, M B

2000-03-13

We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21. This der(21) chromosome has a deletion of 21p and of proximal 21q, whereas the main portion of 21q is duplicated leading to a mirror-symmetric appearance with the mirror axis at the breakpoint. The centromere is only characterized by a secondary constriction (with a centromeric index of a G chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specific or with all human centromeres alpha satellite DNA shows no cross hybridization. Thus, the marker chromosome represents a further example of an "analphoid marker with neocentromere." Molecular analysis using polymorphic markers on chromosome 21 verified a very small monosomic segment of the proximal long arm of chromosome 21, and additionally trisomy of the remaining distal segment. Although trisomic for almost the entire 21q arm, our patient shows no classical Down syndrome phenotype, but only a few minor anomalies found in trisomy 21 and in monosomy of proximal 21q, respectively. Copyright 2000 Wiley-Liss, Inc.

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.

11p15 duplication and 13q34 deletion with Beckwith-Wiedemann syndrome and factor VII deficiency.

Science.gov (United States)

Jurkiewicz, Dorota; Kugaudo, Monika; Tańska, Anna; Wawrzkiewicz-Witkowska, Angelika; Tomaszewska, Agnieszka; Kucharczyk, Marzena; Cieślikowska, Agata; Ciara, Elżbieta; Krajewska-Walasek, Małgorzata

2015-06-01

Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith-Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation-sensitive multiplex ligation-dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay. © 2015 Japan Pediatric Society.

Analysis of autism susceptibility gene loci on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q in Finnish multiplex families.

Science.gov (United States)

Auranen, M; Nieminen, T; Majuri, S; Vanhala, R; Peltonen, L; Järvelä, I

2000-05-01

The role of genetic factors in the etiology of the autistic spectrum of disorders has clearly been demonstrated. Ten chromosomal regions, on chromosomes 1p, 4p, 6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q have potentially been linked to autism.1-8 We have analyzed these chromosomal regions in a total of 17 multiplex families with autism originating from the isolated Finnish population by pairwise linkage analysis and sib-pair analysis. Mild evidence for putative contribution was found only with the 1p chromosomal region in the susceptibility to autism. Our data suggest that additional gene loci exist for autism which will be detectable in and even restricted to the isolated Finnish population.

Constitutional Tandem Duplication of 9q34 that Truncates EHMT1 in a Child with Ganglioglioma

Science.gov (United States)

Cheung, Hannah C.; Yatsenko, Svetlana A.; Kadapakkam, Meena; Legay, Hélène; Su, Jack; Lupski, James R.; Plon, Sharon E.

2011-01-01

Point mutations of EHMT1 or deletions and duplications of chromosome 9q34.3 are found in patients with variable neurologic and developmental disorders. Here, we present a child with congenital cataract, developmental and speech delay who developed a metastatic ganglioglioma with progression to anaplastic astrocytoma. Molecular analysis identified a novel constitutional tandem duplication in 9q34.3 with breakpoints in intron 1 of TRAF2 and intron 16 of EHMT1 generating a fusion transcript predicted to encode a truncated form of EHMT1. The ganglioglioma showed complex chromosomal aberrations with further duplication of the dup9q34. Thus, this unique tandem 9q34.3 duplication may impact brain tumor formation. PMID:21681934

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.

An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome

Directory of Open Access Journals (Sweden)

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.

19q12q13.2 duplication syndrome: neuropsychiatric long-term follow-up of a new case and literature update

Directory of Open Access Journals (Sweden)

Nacinovich R

2017-10-01

Full Text Available Renata Nacinovich,1,2 Nicoletta Villa,3 Fiorenza Broggi,1,2 Cristina Tavaniello,1 Monica Bomba,1 Donatella Conconi,2 Serena Redaelli,2 Elena Sala,3 Marialuisa Lavitrano,2 Francesca Neri1,2 1Childhood and Adolescence Neuropsychiatric Unit, San Gerardo Hospital, 2School of Medicine and Surgery, University of Milano Bicocca, 3Medical Genetics Laboratory, Clinical Pathology Department, San Gerardo Hospital, Monza, Italy Abstract: Genetic syndromes are well characterized by the phenotypic point of view, but little is known about their progression and patients’ quality of life. We report a 10-year neuropsychiatric follow-up of a boy with duplication of chromosome 19. Cytogenetic investigation was requested at the age of 5 years for psychomotor and speech delay. The genomic study identified an 8.17 Mb duplication on chromosome 19q12q13.2. We propose that the long-term follow-up of our patient would help to delineate the neuropsychiatric phenotype associated with 19q duplication. This study could be a model for further long-term research in the neuropsychiatric follow-up of patients with 19q duplication syndrome. Keywords: 19q duplication, neuropsychiatric follow-up, array-CGH

Extra skeletal Soft Tissue Ewing?s Sarcoma with Variant Translocation of Chromosome t (4; 22) (q35; q12)-A Case Report

OpenAIRE

Nagaraj, Prashanth; H, Srinivas C; Rao, Raghavendra; Manohar, Sandesh

2013-01-01

Introduction: Ewing’s sarcomas is a rare primitive neuroectodermal tumour (PNET) which has an annual incidence of 2.9 /million population in USA 1Jeffery Toretsky et al (2008) They are very uncommon in African and Asian population .lt is commonly associated with reciprocal translocation between chromosome 11 and 12 t (11:12) or less frequently the t(21 ;22)(q22;ql 2) translocation. It is highly aggressive tumor which is PAS- and CD99 (MIC2)-positive relatively few variant translocations have ...

Angelman syndrome associated with an inversion of chromosome 15q11.2q24.3

Energy Technology Data Exchange (ETDEWEB)

Greger, V.; Knoll, J.H.M.; Wagstaff, J.; Lalande, M. [and others

1997-03-01

Angelman syndrome (AS) most frequently results from large ({ge}5 Mb) de novo deletions of chromosome 15q11-q13. The deletions are exclusively of maternal origin, and a few cases of paternal uniparental disomy of chromosome 15 have been reported. The latter finding indicates that AS is caused by the absence of a maternal contribution to the imprinted 15q11-q13 region. Failure to inherit a paternal 15q11-q13 contribution results in the clinically distinct disorder of Prader-Willi syndrome. Cases of AS resulting from translocations or pericentric inversions have been observed to be associated with deletions, and there have been no confirmed reports of balanced rearrangements in AS. We report the first such case involving a paracentric inversion with a breakpoint located {approximately}25 kb proximal to the reference marker D15S10. This inversion has been inherited from a phenotypically normal mother. No deletion is evident by molecular analysis in this case, by use of cloned fragments mapped to within {approximately}1 kb of the inversion breakpoint. Several hypotheses are discussed to explain the relationship between the inversion and the AS phenotype. 47 refs., 3 figs.

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.

Genomic Anatomy of a Premier Major Histocompatibility Complex Paralogous Region on Chromosome 1q21–q22

Science.gov (United States)

Shiina, Takashi; Ando, Asako; Suto, Yumiko; Kasai, Fumio; Shigenari, Atsuko; Takishima, Nobusada; Kikkawa, Eri; Iwata, Kyoko; Kuwano, Yuko; Kitamura, Yuka; Matsuzawa, Yumiko; Sano, Kazumi; Nogami, Masahiro; Kawata, Hisako; Li, Suyun; Fukuzumi, Yasuhito; Yamazaki, Masaaki; Tashiro, Hiroyuki; Tamiya, Gen; Kohda, Atsushi; Okumura, Katsuzumi; Ikemura, Toshimichi; Soeda, Eiichi; Mizuki, Nobuhisa; Kimura, Minoru; Bahram, Seiamak; Inoko, Hidetoshi

2001-01-01

Human chromosomes 1q21–q25, 6p21.3–22.2, 9q33–q34, and 19p13.1–p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21–25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21–q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides. [The nucleotide sequence data reported in this paper have been submitted to the DDBJ, EMBL, and GenBank databases under

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 M; Agergaard, Peter; Olesen, Charlotte

2010-01-01

The 22q11 deletion syndrome, which is caused by a 1.5- to 3.0-megabase hemizygous deletion in chromosome 22q11.2, has a prevalence of 1/2000 to 1/4000. However, the syndrome presents with highly variable phenotypes and thus may be underestimated among Danish newborns. To establish a true incidenc...

An Fgf8 Mouse Mutant Phenocopies Human 22q11 Deletion Syndrome

OpenAIRE

Frank, Deborah U.; Fotheringham, Lori K.; Brewer, Judson A.; Muglia, Louis J.; Tristani-Firouzi, Martin; Capecchi, Mario R.; Moon, Anne M.

2002-01-01

Deletion of chromosome 22q11, the most common microdeletion detected in humans, is associated with a life-threatening array of birth defects. Although 90% of affected individuals share the same three megabase deletion, their phenotype is highly variable and includes craniofacial and cardiovascular anomalies, hypoplasia or aplasia of the thymus with associated deficiency of T cells, hypocalcemia with hypoplasia or aplasia of the parathyroids, and a variety of central nervous system abnormaliti...

Síndrome de deleção 22q11 e cardiopatias congênitas complexas 22q11.2 deletion syndrome and complex congenital heart defects

Directory of Open Access Journals (Sweden)

Rafael Fabiano Machado Rosa

2011-02-01

Full Text Available OBJETIVO: Verificar a frequência da síndrome de deleção 22q11 (SD22q11 entre pacientes portadores de cardiopatia congênita do tipo complexa. MÉTODOS: A amostra foi constituída por uma coorte prospectiva e consecutiva de pacientes com cardiopatia complexa em sua primeira hospitalização em uma unidade de tratamento intensivo cardiológica de um hospital pediátrico. Para cada paciente foi preenchida uma ficha de avaliação, com coleta de dados clínicos, e realizado o cariótipo de alta resolução e técnica de hibridização in situ fluorescente (FISH com pesquisa de microdeleção 22q11. Os defeitos cardíacos foram classificados por um cardiologista participante do estudo. RESULTADOS: A amostra foi composta de 66 pacientes. Quanto à análise cariotípica, alterações foram observadas em cinco pacientes (7,6%; contudo, nenhum deles apresentava deleção 22q11. A avaliação pela técnica de FISH pôde ser realizada com sucesso em 65 pacientes, sendo que a microdeleção 22q11 foi identificada em dois (3,1%. Dos 66 pacientes com defeitos complexos, 52 eram portadores de malformações do tipo conotruncal, sendo que em 51 a pesquisa para microdeleção 22q11 foi realizada. Os dois pacientes portadores da microdeleção 22q11 fizeram parte deste grupo, representando uma frequência de 3,9%. Eles apresentavam tetralogia de Fallot. CONCLUSÃO: A SD22q11 é uma anormalidade frequente entre pacientes com cardiopatias congênitas complexas e conotruncais. Variações da frequência da SD22q11 entre os estudos parecem estar associadas, principalmente, com a forma adotada para a seleção da amostra e às características da população em análise.OBJECTIVE: Investigate the frequency of 22q11 deletion syndrome among patients with complex congenital heart disease. METHODS: A prospective and consecutive cohort of patients with complex heart defects was evaluated in their first hospitalization at a cardiac intensive care unit of a pediatric

Inversion of chromosome 7q22 and q36 as a sole abnormality presenting in myelodysplastic syndrome: a case report.

Science.gov (United States)

Kaneko, Hiroto; Shimura, Kazuho; Kuwahara, Saeko; Ohshiro, Muneo; Tsutsumi, Yasuhiko; Iwai, Toshiki; Horiike, Shigeo; Yokota, Shouhei; Ohkawara, Yasuo; Taniwaki, Masafumi

2014-08-05

Deletions of chromosome 7 are often detected in myelodysplastic syndrome. The most commonly deleted segments are clustered at band 7q22. A critical gene is therefore suggested to be located in this region. We report a patient with myelodysplastic syndrome whose marrow cells carried an inversion of 7q22 and q36 as a sole karyotypic abnormality. How this extremely rare chromosomal aberration contributes to the pathogenesis of myelodysplastic syndrome should be clarified by accumulating clinical data of such cases. A 74-year-old Japanese man presented with pancytopenia incidentally detected by routine medical check-up. His complete blood cell counts revealed that his white blood cells had decreased to 2100/mm3, neutrophils 940/mm3, red blood cells 320×104/mm3, hemoglobin 11.1g/dL, hematocrit 33.1%, and platelets 12.6×104/mm3. Bone marrow examination showed normal cellularity with nucleated cells of 9.4×104/mm3. The proportion of blasts was 4%. A morphological examination showed only basophilic stippling of erythroblasts which was seen as dysplasia. According to World Health Organization classification, the diagnosis was myelodysplastic syndrome-u. Karyotypic analysis showed 46,XY,inv(7)(q22q36) in all of 20 metaphases examined. Additional analysis revealed the karyotype of his lymphocytes was 46,XY. He is asymptomatic and cytopenia has slowly progressed. To the best of our knowledge, this karyotype from a clinical sample of de novo malignancies has never been documented although the identical karyotype from secondary myelodysplastic syndrome was reported. Despite the extremely low frequency, inversion of 7q22 appears to play a crucial role for myelodysplastic syndrome in this patient.

Comprehensive review of the duplication 3q syndrome and report of a patient with Currarino syndrome and de novo duplication 3q26.32-q27.2.

Science.gov (United States)

Dworschak, G C; Crétolle, C; Hilger, A; Engels, H; Korsch, E; Reutter, H; Ludwig, M

2017-05-01

Partial duplications of the long arm of chromosome 3, dup(3q), are a rare but well-described condition, sharing features of Cornelia de Lange syndrome. Around two thirds of cases are derived from unbalanced translocations, whereas pure dup(3q) have rarely been reported. Here, we provide an extensive review of the literature on dup(3q). This search revealed several patients with caudal malformations and anomalies, suggesting that caudal malformations or anomalies represent an inherent phenotypic feature of dup(3q). In this context, we report a patient with a pure de novo duplication 3q26.32-q27.2. The patient had the clinical diagnosis of Currarino syndrome (CS) (characterized by the triad of sacral anomalies, anorectal malformations and a presacral mass) and additional features, frequently detected in patients with a dup(3q). Mutations within the MNX1 gene were found to be causative in CS but no MNX1 mutation could be detected in our patient. Our comprehensive search for candidate genes located in the critical region of the duplication 3q syndrome, 3q26.3-q27, revealed a so far neglected phenotypic overlap of dup(3q) and the Pierpont syndrome, associated with a mutation of the TBL1XR1 gene on 3q26.32. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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

Directory of Open Access Journals (Sweden)

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.

Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and review of the potential link between the constitutional t(11;22) and cancer.

Science.gov (United States)

Doyen, Jérôme; Carpentier, Xavier; Haudebourg, Juliette; Hoch, Benjamin; Karmous-Benailly, Houda; Ambrosetti, Damien; Fabas, Thibault; Amiel, Jean; Lambert, Jean-Claude; Pedeutour, Florence

2012-11-01

We observed a t(11;22)(q23-24;q11.2-12) and monosomy 3 in renal tumor cells from a 72-year-old man. The hypothesis of a primitive peripheral neuroectodermal tumor (PPNET) located in the kidney was promptly excluded: Histologically, the tumor was a clear cell renal cell carcinoma (RCC) and we did not observe an EWSR1 gene rearrangement. The constitutional origin of this alteration was established. We report on the second case of RCC in a patient with a constitutional t(11;22). The t(11;22)(q23;q11.2) is the main recurrent germline translocation in humans. Unbalanced translocation can be transmitted to the progeny and can cause Emanuel syndrome. Our observation alerts cancer cytogeneticists to the fortuitous discovery of the constitutional t(11;22) in tumor cells. This translocation appears grossly similar to the t(11;22)(q24;q12) of PPNET and should be evoked if present in all cells of a tumor other than PPNET. This is important when providing appropriate genetic counseling. Moreover, the potential oncogenic role of the t(11;22) and its predisposing risk of cancer are under debate. The family history of the patient revealed a disabled brother who died at an early age from colon cancer and a sister with breast cancer. This observation reopens the issue of a link between the constitutional t(11;22) and cancer, and the utility of cancer prevention workups for t(11;22) carriers. Copyright © 2012 Elsevier Inc. All rights reserved.

Chromosome 15q overgrowth syndrome: Prenatal diagnosis, molecular cytogenetic characterization, and perinatal findings in a fetus with dup(15(q26.2q26.3

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2011-09-01

Conclusion: The present case provides evidence for prenatal overgrowth, craniosynostosis, and characteristic facial dysmorphism in association with a duplication of 15q26.2→q26.3 and a duplication of the IGF1R gene. Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of the chromosome 15q overgrowth syndrome.

Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11 deletion syndrome

Directory of Open Access Journals (Sweden)

Beverly A. Karpinski

2014-02-01

Full Text Available We assessed feeding-related developmental anomalies in the LgDel mouse model of chromosome 22q11 deletion syndrome (22q11DS, a common developmental disorder that frequently includes perinatal dysphagia – debilitating feeding, swallowing and nutrition difficulties from birth onward – within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA signaling, prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V, glossopharyngeal (IX or vagus (X cranial nerves (CNs that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to those in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS.

A de novo 11p12-p15.4 duplication in a patient with pharmacoresistant epilepsy, mental retardation, and dysmorphisms.

Science.gov (United States)

Coppola, Antonietta; Striano, Pasquale; Gimelli, Stefania; Ciampa, Clotilde; Santulli, Lia; Caranci, Ferdinando; Zuffardi, Orsetta; Gimelli, Giorgio; Striano, Salvatore; Zara, Federico

2010-03-01

We report a 22-year-old male patient with pharmacoresistant epilepsy, mental retardation and dysmorphisms. Standard cytogenetic analysis revealed a de novo interstitial duplication of the short arm of chromosome 11 (11p). High density array-CGH analysis showed that the rearrangement spans about 35Mb on chromosome 11p12-p15.4. Duplications of 11p are rare and usually involve the distal part of the chromosome arm (11p15), being not associated with epilepsy, whereas our patient showed a unique epileptic phenotype associated with mental retardation and dysmorphic features. The role of some rearranged genes in epilepsy pathogenesis in this patient is also discussed.

Childhood cognitive development in 22q11.2 deletion syndrome: case-control study.

Science.gov (United States)

Chawner, Samuel J R A; Doherty, Joanne L; Moss, Hayley; Niarchou, Maria; Walters, James T R; Owen, Michael J; van den Bree, Marianne B M

2017-10-01

Background 22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of childhood as well as adult psychiatric disorders, in particular schizophrenia. Childhood cognitive deterioration in 22q11.2DS has previously been reported, but only in studies lacking a control sample. Aims To compare cognitive trajectories in children with 22q11.2DS and unaffected control siblings. Method A longitudinal study of neurocognitive functioning (IQ, executive function, processing speed and attention) was conducted in children with 22q11.2DS ( n = 75, mean age time 1 ( T 1 ) 9.9, time 2 ( T 2 ) 12.5) and control siblings ( n = 33, mean age T 1 10.6, T 2 13.4). Results Children with 22q11.2DS exhibited deficits in all cognitive domains. However, mean scores did not indicate deterioration. When individual trajectories were examined, some participants showed significant decline over time, but the prevalence was similar for 22q11.2DS and control siblings. Findings are more likely to reflect normal developmental fluctuation than a 22q11.2DS-specific abnormality. Conclusions Childhood cognitive deterioration is not associated with 22q11.2DS. Contrary to previous suggestions, we believe it is premature to recommend repeated monitoring of cognitive function for identifying individual children with 22q11.2DS at high risk of developing schizophrenia. © The Royal College of Psychiatrists 2017.

Complex Variant t(9;22 Chromosome Translocations in Five Cases of Chronic Myeloid Leukemia

Directory of Open Access Journals (Sweden)

Ana Valencia

2009-01-01

Full Text Available The Philadelphia (Ph1 chromosome arising from the reciprocal t(9;22 translocation is found in more than 90% of chronic myeloid leukemia (CML patients and results in the formation of the chimeric fusion gene BCR-ABL. However, a small proportion of patients with CML have simple or complex variants of this translocation, involving various breakpoints in addition to 9q34 and 22q11. We report five CML cases carrying variant Ph translocations involving both chromosomes 9 and 22 as well as chromosomes 3, 5, 7, 8, or 10. G-banding showed a reciprocal three-way translocation involving 3q21, 5q31, 7q32, 8q24, and 10q22 bands. BCR-ABL fusion signal on der(22 was found in all of the cases by FISH.

Use of a human chromosome 11 radiation hybrid panel to map markers at 11q13

International Nuclear Information System (INIS)

Withers, D.; Richard, C. III; Meeker, T.C.; Maurer, S.; Evans, G.; Myers, R.M.; Cox, D.R.

1990-01-01

A human/hamster hybrid cell line containing human chromosome 11 was X-irradiated and 102-independent derivative lines were recovered. These 'radiation hybrids' contain random fragments of human chromosome 11. This radiation hybrid panel was used to score the retention of markers at band 11q13. Statistical analysis of marker co-retention patterns in the radiation hybrid panel permits a preliminary ordering and mapping of the markers used. The best order for six scored markers is: proximal - CD5 - CD20 - PGA - HST - BCL1 - SEA - distal. Additional markers are currently being scored. The six 11q13 markers above are spread over approximately 10-12 mB of DNA. The mapping data has implications for the identification of the bcl-1 gene. bcl-1 is the site of chromosome breakage in translocations associated with B lymphocytic malignancy. bcl-1 markers map at least 4 Mb away from any of four genes previously hypothesized to be activated by such translocations, thereby making them unlikely candidates for activation

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

Siblings with opposite chromosome constitutions, dup(2q)/del(7q) and del(2q)/dup(7q).

Science.gov (United States)

Shim, Sung Han; Shim, Jae Sun; Min, Kyunghoon; Lee, Hee Song; Park, Ji Eun; Park, Sang Hee; Hwang, Euna; Kim, Minyoung

2014-01-15

Chromosome 7q36 microdeletion syndrome is a rare genomic disorder characterized by underdevelopment of the brain, microcephaly, anomalies of the sex organs, and language problems. Developmental delay, intellectual disability, autistic spectrum disorders, BDMR syndrome, and unusual facial morphology are the key features of the chromosome 2q37 microdeletion syndrome. A genetic screening for two brothers with global developmental delay using high-resolution chromosomal analysis and subtelomeric multiplex ligation-dependent probe amplification revealed subtelomeric rearrangements on the same sites of 2q37.2 and 7q35, with reversed deletion and duplication. Both of them showed dysmorphic facial features, severe disability of physical and intellectual development, and abnormal genitalia with differential abnormalities in their phenotypes. The family did not have abnormal genetic phenotypes. According to the genetic analysis of their parents, adjacent-1 segregation from their mother's was suggested as a mechanism of their gene mutation. By comparing the phenotypes of our patients with previous reports on similar patients, we tried to obtain the information of related genes and their chromosomal locations. © 2013.

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.

Neurocognitive profile in psychotic versus nonpsychotic individuals with 22q11.2 deletion syndrome.

Science.gov (United States)

Weinberger, Ronnie; Yi, James; Calkins, Monica; Guri, Yael; McDonald-McGinn, Donna M; Emanuel, Beverly S; Zackai, Elaine H; Ruparel, Kosha; Carmel, Miri; Michaelovsky, Elena; Weizman, Abraham; Gur, Ruben C; Gur, Raquel E; Gothelf, Doron

2016-10-01

The 22q11.2 deletion syndrome (22q11DS) is associated with increased rates of psychotic disorders and cognitive deficits, but large scale studies are needed to elucidate their interaction. The objective of this two-center study was to identify the neurocognitive phenotype of individuals with 22q11DS and psychotic disorders. We hypothesized that psychotic 22q11DS individuals compared to nonpsychotic deleted individuals would have more severe neurocognitive deficits, especially in executive function and social cognition. These deficits would be present when compared to IQ- matched individuals with Williams Syndrome (WS). Three groups were ascertained from the Tel Aviv and Philadelphia centers: 22q11DS individuals with a psychotic disorder (n=31), nonpsychotic 22q11DS (n=86) and typically-developing controls (TD, n=828). In Tel Aviv a group of individuals with WS (n=18) matched in IQ to the 22q11DS psychotic group was also included. The Penn Computerized Neurocognitive Battery (CNB) was used to assess a wide-range of cognitive functions and all patients underwent structured psychiatric evaluations. 22q11DS individuals performed poorly on all CNB domains compared to TD. Participants with 22q11DS and psychosis, compared to nonpsychotic 22q11DS, had more severe deficits in global neurocognitive performance (GNP), executive function, social cognition and episodic memory domains. The primary deficits were also significant when comparing the Tel Aviv 22q11DS psychotic group to IQ-matched individuals with WS. In conclusion, 22q11DS individuals with a psychotic disorder have specific neurocognitive deficits that are reliably identified cross nationality using the CNB. These cognitive dysfunctions should be further studied as potential endophenotypes of psychosis in 22q11DS and as targets for intervention. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13. 1-q21. 1 and mouse chromosome 5

Energy Technology Data Exchange (ETDEWEB)

Kaiser, U.B.; Dushkin, H.; Beier, D.R.; Chin, W.W. (Harvard Medical School, Boston, MA (United States)); Altherr, M.R. (Los Alamos National Lab., NM (United States))

1994-04-01

The gonadotropin-releasing hormone receptor (GRHR) is a G-protein-coupled receptor on the cell surface of pituitary gonadotropes, where it serves to transduce signals from the extracellular ligand, the hypothalamic factor gonadotropin-releasing hormone, and to modulate the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. The authors have localized the GRHR gene to the q13.1-q21.1 region of the human chromosome 4 using mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4. Furthermore, using linkage analysis of single-strand conformational polymorphisms, the murine GRHR gene was localized to mouse chromosome 5, linked to the endogenous retroviral marker Pmv-11. This is consistent with the evolutionary conservation of homology between these two regions, as has been previously suggested from comparative mapping of several other loci. The localization of the GRHR gene may be useful in the study of disorders of reproduction. 22 refs., 2 figs.

Allelic variations at the haploid TBX1 locus do not influence the cardiac phenotype in cases of 22q11 microdeletion.

Science.gov (United States)

Voelckel, Marie-Antoinette; Girardot, Lydie; Giusiano, Bernard; Levy, Nicolas; Philip, Nicole

2004-01-01

Microdeletion at the 22q11 locus is characterised by a high clinical variability. Congenital heart defects (CHD) are the most life-threatening manifestations of the syndrome and affect approximately 50% of patients carrying the deleted chromosome 22. The causes of this phenotype variability remain unknown although several hypotheses have been raised. It has been suggested that allelic variations at the haploid locus could modify the phenotypic expression. Regarding this hypothesis, TBX1 was thought to be a major candidate to the cardiac phenotype or its severity in patients carrying the 22q11 microdeletion. A mutational screening was performed in this gene, in a series of 39 deleted patients, with and without CHD. The results indicate that mutations in TBX1 are not likely to be involved in the cardiac phenotype observed in del22q11 patients.

Fluorescence in situ hybridization (FISH screening for the 22q11.2 deletion in patients with clinical features of velocardiofacial syndrome but without cardiac anomalies

Directory of Open Access Journals (Sweden)

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.

A molecularly defined duplication set for the X chromosome of Drosophila melanogaster

Energy Technology Data Exchange (ETDEWEB)

Venken, Koen J. T.; Popodi, Ellen; Holtzman, Stacy L.; Schulze, Karen L.; Park, Soo; Carlson, Joseph W.; Hoskins, Roger A.; Bellen, Hugo J.; Kaufman, Thomas C.

2010-07-22

We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using C31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.

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.

[Recombinant chromosome 4 with partial 4p deletion and 4q duplication inherited from paternal pericentric inversion].

Science.gov (United States)

Mun, Se Jin; Cho, Eun Hae; Chey, Myoung-Jae; Shim, Gyu-Hong; Shin, Bo-Moon; Lee, Rae-Kyung; Ko, Ji-Kyung; Yoo, Soo Jin

2010-02-01

Pericentric inversion of chromosome 4 can give rise to 2 alternate recombinant (rec) chromosomesby duplication or deletion of 4p. The deletion of distal 4p manifests as Wolf-Hirschhorn syndrome (WHS). Here, we report the molecular cytogenetic findings and clinical manifestations observed in an infant with 46,XX,rec(4)dup(4q)inv(4)(p16q31.3)pat. The infant was delivered by Cesarean section at the 33rd week of gestation because pleural effusion and polyhydramnios were detected on ultrasonography. At birth, the infant showed no malformation or dysfunction, except for a preauricular skin tag. Array comparative genomic hybridization analysis of neonatal peripheral blood samples showed a gain of 38 Mb on 4q31.3-qter and a loss of 3 Mb on 4p16.3, and these results were consistent with WHS. At the last follow-up at 8 months of age (corrected age, 6 months), the infant had not achieved complete head control.

A case of schizophrenia comorbid for tetralogy of Fallot treated with clozapine: further considerations on a role for 22q.11.2 in the proneness for seizures

Directory of Open Access Journals (Sweden)

Kashiwagi H

2017-08-01

Full Text Available Hiroko Kashiwagi,1 Satoru Ikezawa,2 Tomiki Sumiyoshi,3 Atsuko Kadono,4 Kazuhiko Segawa,5 Kazuyoshi Takeda,1 Mayu Omori,1 Hisako Taguchi,1 Naotsugu Hirabayashi1 1Department of Forensic Psychiatry, 2Department of Psychiatry, 3Department of Clinical Epidemiology, Translational Medical Center, National Center Hospital of Neurology and Psychiatry, Kodaira, Tokyo, 4Saitama Psychiatric Medical Center, Kitaadatigun, Saitama, 5Department of General Medicine, National Center Hospital of Neurology and Psychiatry, Kodaira, Tokyo, Japan Abstract: We present a case of schizophrenia comorbid for tetralogy of Fallot, without chromosome 22q.11.2 deletion or duplication, treated successfully with a combination of clozapine and antiepileptic drugs. Although clozapine by itself initially triggered convulsive seizures, we continued it with co-administration of valproate and topiramate. This combined treatment did not affect cardiac function of the patient, who experienced a favorable clinical course in terms of symptomatology and functional outcomes. To our knowledge, we provide the first report on a patient with tetralogy of Fallot, in whom 22q.11.2 was not deleted and clozapine-induced seizures were observed. Keywords: schizophrenia, clozapine, tetralogy of Fallot, seizure, copy number variants

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

Referential communication abilities in children with 22q11.2 deletion syndrome.

Science.gov (United States)

Van Den Heuvel, Ellen; ReuterskiöLd, Christina; Solot, Cynthia; Manders, Eric; Swillen, Ann; Zink, Inge

2017-10-01

This study describes the performance on a perspective- and role-taking task in 27 children, ages 6-13 years, with 22q11.2 deletion syndrome (22q11.2DS). A cross-cultural design comparing Dutch- and English-speaking children with 22q11.2DS explored the possibility of cultural differences. Chronologically age-matched and younger typically developing (TD) children matched for receptive vocabulary served as control groups to identify challenges in referential communication. The utterances of children with 22q11.2DS were characterised as short and simple in lexical and grammatical terms. However, from a language use perspective, their utterances were verbose, ambiguous and irrelevant given the pictured scenes. They tended to elaborate on visual details and conveyed off-topic, extraneous information when participating in a barrier-game procedure. Both types of aberrant utterances forced a listener to consistently infer the intended message. Moreover, children with 22q11.2DS demonstrated difficulty selecting correct speech acts in accordance with contextual cues during a role-taking task. Both English- and Dutch-speaking children with 22q11.2DS showed impoverished information transfer and an increased number of elaborations, suggesting a cross-cultural syndrome-specific feature.

Characterization of human chromosome 22 : Cloning of breakpoints of the constitutional translocation t(11;22)(q23;q11) and detection of small constitutional delections by microarray CGH

OpenAIRE

Tapia Paez, Isabel

2003-01-01

Chromosome 22 is the second smallest human chromosome, composing approximately 1.5% of the genome. The short arm of this acrocentric chromosome harbors ribosomal genes and the long arm contains the protein coding genes. This chromosome is gene-rich in comparison to the majority of other chromosomes, containing approximately 600 so far characterized genes. Many of these are involved in the etiology of a wide spectrum of diseases such as congenital and psychiatric disorders as...

A molecularly defined duplication set for the X chromosome of Drosophila melanogaster.

Science.gov (United States)

Venken, Koen J T; Popodi, Ellen; Holtzman, Stacy L; Schulze, Karen L; Park, Soo; Carlson, Joseph W; Hoskins, Roger A; Bellen, Hugo J; Kaufman, Thomas C

2010-12-01

We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using ΦC31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.

Heart defects and other features of the 22q11 distal deletion syndrome

DEFF Research Database (Denmark)

Fagerberg, Christina Ringmann; Graakjaer, Jesper; Heinl, Ulrike D

2013-01-01

patients with 22q11 distal deletions, of whom two have complex congenital heart malformation, thus broadening the phenotypic spectrum. We compare cardiac malformations reported in 22q11 distal deletion to those reported in the common 22q11 deletion syndrome. We also review the literature for patients...... with 22q11 distal deletions, and discuss the possible roles of haploinsufficiency of the MAPK1 gene. We find the most frequent features in 22q11 distal deletion to be developmental delay or learning disability, short stature, microcephalus, premature birth with low birth weight, and congenital heart...... malformation ranging from minor anomalies to complex malformations. Behavioral problems are also seen in a substantial portion of patients. The following dysmorphic features are relatively common: smooth philtrum, abnormally structured ears, cleft palate/bifid uvula, micro-/retrognathia, upslanting palpebral...

[Grave's disease in children with 22q11 deletion. Report of three cases].

Science.gov (United States)

Gosselin, J; Lebon-Labich, B; Lucron, H; Marçon, F; Leheup, B

2004-12-01

Hypothyroidism is a well recognized complication of 22q11.2 deletion syndrome. Auto-immune hyperthyroidism is less common. We report three patients with a 22q11.2 deletion and Graves' disease diagnosed at age 17, 14 and 11 years, respectively. The clinical and biological presentation was typical for auto-immune hyperthyroidism. Graves' disease should be periodically sought during the follow-up program of patients with 22q11.2 deletion syndrome.

Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome.

Science.gov (United States)

Murray, Jeffrey C; Donahue, David J; Malik, Saleem I; Dzurik, Yvette B; Braly, Emily Z; Dougherty, Margaret J; Eaton, Katherine W; Biegel, Jaclyn A

2011-05-01

DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.

Targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae.

Science.gov (United States)

Takahashi, Tadashi; Sato, Atsushi; Ogawa, Masahiro; Hanya, Yoshiki; Oguma, Tetsuya

2014-08-01

We describe here the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had a 5'-deleted pyrG upstream of the region targeted for tandem chromosomal duplication and a 3'-deleted pyrG downstream of the target region. Consequently,strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks(DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under nonselective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method.

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.

Behavioral phenotype in children with 22q11Ds : Agreement between parents and teachers

NARCIS (Netherlands)

Klaassen, Petra W J; Duijff, Sasja N.; Sinnema, Gerben; Beemer, Frits A.; Swanenburg de Veye, Henriëtte F N; Vorstman, Jacob A S

2015-01-01

Patients with the 22q11-deletion syndrome (22q11DS) are at an increased risk of developing schizophrenia. Besides the effects of genetic variation, environmental factors could also be important in modifying the risk of schizophrenia in 22q11DS patients. In particular, previous studies have shown the

Multisite Semiautomated Clinical Data Repository for Duplication 15q Syndrome: Study Protocol and Early Uses.

Science.gov (United States)

Ajayi, Oluwaseun Jessica; Smith, Ebony Jeannae; Viangteeravat, Teeradache; Huang, Eunice Y; Nagisetty, Naga Satya V Rao; Urraca, Nora; Lusk, Laina; Finucane, Brenda; Arkilo, Dimitrios; Young, Jennifer; Jeste, Shafali; Thibert, Ronald; Reiter, Lawrence T

2017-10-18

Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a rare disorder caused by duplications of chromosome 15q11.2-q13.1, resulting in a wide range of developmental disabilities in affected individuals. The Dup15q Alliance is an organization that provides family support and promotes research to improve the quality of life of patients living with Dup15q syndrome. Because of the low prevalence of this condition, the establishment of a single research repository would have been difficult and more time consuming without collaboration across multiple institutions. The goal of this project is to establish a national deidentified database with clinical and survey information on individuals diagnosed with Dup15q syndrome. The development of a multiclinic site repository for clinical and survey data on individuals with Dup15q syndrome was initiated and supported by the Dup15q Alliance. Using collaborative workflows, communication protocols, and stakeholder engagement tools, a comprehensive database of patient-centered information was built. We successfully established a self-report populating, centralized repository for Dup15q syndrome research. This repository also resulted in the development of standardized instruments that can be used for other studies relating to developmental disorders. By standardizing the data collection instruments, it allows us integrate our data with other national databases, such as the National Database for Autism Research. A substantial portion of the data collected from the questionnaires was facilitated through direct engagement of participants and their families. This allowed for a more complete set of information to be collected with a minimal turnaround time. We developed a repository that can efficiently be mined for shared clinical phenotypes observed at multiple clinic sites and used as a springboard for future clinical and basic research studies. ©Oluwaseun Jessica Ajayi, Ebony Jeannae Smith, Teeradache Viangteeravat

Chromosome 22 microdeletion in children with syndromic ...

African Journals Online (AJOL)

Cytogenetic study and fluorescence in situ hybridization (FISH) were performed in the patients. The study revealed that 2 patients were with chromosomal aberrations [one with 46,XY, add (13)(p13) & the other with 47,XX,+13]. In addition, FISH revealed 4 patients (20%) with 22q11.2 microdeletion syndrome. The congenital ...

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

Haploinsufficiency of the 22q11.2 microdeletion gene Mrpl40 disrupts short-term synaptic plasticity and working memory through dysregulation of mitochondrial calcium.

Science.gov (United States)

Devaraju, P; Yu, J; Eddins, D; Mellado-Lagarde, M M; Earls, L R; Westmoreland, J J; Quarato, G; Green, D R; Zakharenko, S S

2017-09-01

Hemizygous deletion of a 1.5- to 3-megabase region on chromosome 22 causes 22q11.2 deletion syndrome (22q11DS), which constitutes one of the strongest genetic risks for schizophrenia. Mouse models of 22q11DS have abnormal short-term synaptic plasticity that contributes to working-memory deficiencies similar to those in schizophrenia. We screened mutant mice carrying hemizygous deletions of 22q11DS genes and identified haploinsufficiency of Mrpl40 (mitochondrial large ribosomal subunit protein 40) as a contributor to abnormal short-term potentiation (STP), a major form of short-term synaptic plasticity. Two-photon imaging of the genetically encoded fluorescent calcium indicator GCaMP6, expressed in presynaptic cytosol or mitochondria, showed that Mrpl40 haploinsufficiency deregulates STP via impaired calcium extrusion from the mitochondrial matrix through the mitochondrial permeability transition pore. This led to abnormally high cytosolic calcium transients in presynaptic terminals and deficient working memory but did not affect long-term spatial memory. Thus, we propose that mitochondrial calcium deregulation is a novel pathogenic mechanism of cognitive deficiencies in schizophrenia.

Identification of susceptibility genes for bipolar affective disorder and schizophrenia on chromosome 22q13

DEFF Research Database (Denmark)

Severinsen, Jacob Eg

2006-01-01

Linkage analyses suggest that chromosome 22q12-13 may harbor one or more shared susceptibility loci for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of distantly related cases and control individuals from the Faeroe Islands our group has previously reported that chromosome 22...... samples (total of 1,751 individuals), and by bioinformatic and expression analyses of a subset of disease associated genes and gene variants. In total 67 single nucleotide polymorphisms (SNPs) located in 18 positional candidate genes, and 4 microsattelite markers were investigated, using a Scottish case...

Neuropeptide Y receptor genes on human chromosome 4q31-q32 map to conserved linkage groups on mouse chromosomes 3 and 8

Energy Technology Data Exchange (ETDEWEB)

Lutz, C.M.; Frankel, W.N. [Jackson Lab., Bar Harbor, ME (United States); Richards, J.E. [Univ. of Michigan Medical School, Ann Arbor, MI (United States)] [and others

1997-05-01

Npy1r and Npy2r, the genes encoding mouse type 1 and type 2 neuropeptide Y receptors, have been mapped by interspecific backcross analysis. Previous studies have localized the human genes encoding these receptors to chromosome 4q31-q32. We have now assigned Npy1r and Npy2r to conserved linkage groups on mouse Chr 8 and Chr 3, respectively, which correspond to the distal region of human chromosome 4q. Using yeast artificial chromosomes, we have estimated the distance between the human genes to be approximately 6 cM. Although ancient tandem duplication events may account for some closely spaced G-protein-coupled receptor genes, the large genetic distance between the human type 1 and type 2 neuropeptide Y receptor genes raises questions about whether this mechanism accounts for their proximity. 20 refs., 1 fig.

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.

Frontonasal malformation with tetralogy of Fallot associated with a submicroscopic deletion of 22q11

Energy Technology Data Exchange (ETDEWEB)

Stratton, R.F. [South Texas Genetics Center, San Antonio, TX (United States); Payne, R.M. [Central Texas Genetics Center, Austin, TX (United States)

1997-03-31

We report on a 14-month-old girl with bifid nasal tip and tetralogy of Fallot. Several similar patients have been described with CNS or eye abnormalities. Chromosome analysis with FISH, using Oncor DiGeorge probes, confirmed a submicroscopic deletion of 22q11. Many patients with Shprintzen (velo-cardio-facial) syndrome have a similar deletion with conotruncal cardiac defects and an abnormal nasal shape, suggesting that a gene in this area, possibly affecting neural crest cells, influences facial and other midline development. 13 refs., 1 fig.

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.

Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes.

Science.gov (United States)

Dunaway, Keith W; Islam, M Saharul; Coulson, Rochelle L; Lopez, S Jesse; Vogel Ciernia, Annie; Chu, Roy G; Yasui, Dag H; Pessah, Isaac N; Lott, Paul; Mordaunt, Charles; Meguro-Horike, Makiko; Horike, Shin-Ichi; Korf, Ian; LaSalle, Janine M

2016-12-13

Rare variants enriched for functions in chromatin regulation and neuronal synapses have been linked to autism. How chromatin and DNA methylation interact with environmental exposures at synaptic genes in autism etiologies is currently unclear. Using whole-genome bisulfite sequencing in brain tissue and a neuronal cell culture model carrying a 15q11.2-q13.3 maternal duplication, we find that significant global DNA hypomethylation is enriched over autism candidate genes and affects gene expression. The cumulative effect of multiple chromosomal duplications and exposure to the pervasive persistent organic pollutant PCB 95 altered methylation of more than 1,000 genes. Hypomethylated genes were enriched for H2A.Z, increased maternal UBE3A in Dup15q corresponded to reduced levels of RING1B, and bivalently modified H2A.Z was altered by PCB 95 and duplication. These results demonstrate the compounding effects of genetic and environmental insults on the neuronal methylome that converge upon dysregulation of chromatin and synaptic genes. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe Islands

DEFF Research Database (Denmark)

Jorgensen, T H; Børglum, A D; Mors, O

2002-01-01

Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe...... Islands were typed for 35 evenly distributed polymorphic markers on 22q in a search for shared risk genes in the two disorders. No single marker was strongly associated with either disease, but five two-marker segments that cluster within two regions on the chromosome have haplotypes occurring...

Familial partial duplication (1)(p21p31)

Energy Technology Data Exchange (ETDEWEB)

Hoechstetter, L.; Soukup, S.; Schorry, E.K. [Children`s Hospital Research Foundation, Cincinnati, OH (United States)

1995-11-20

A partial duplication (1)(p21p31), resulting from a maternal direct insertion (13,1) (q22p21p31), was found in a 30-year-old woman with mental retardation, cleft palate, and multiple minor anomalies. Two other affected and deceased relatives were presumed to have the same chromosome imbalance. Duplication 1p cases are reviewed. 8 refs., 5 figs., 1 tab.

A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements.

Science.gov (United States)

Kohmoto, Tomohiro; Okamoto, Nana; Naruto, Takuya; Murata, Chie; Ouchi, Yuya; Fujita, Naoko; Inagaki, Hidehito; Satomura, Shigeko; Okamoto, Nobuhiko; Saito, Masako; Masuda, Kiyoshi; Kurahashi, Hiroki; Imoto, Issei

2017-01-01

Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented. Here, we report on the chromosomal microarray (CMA)-based identification of the first known case with concurrent interstitial duplication at 1q42.12-q42.2 and triplication at 1q42.2-q43 followed by isoUPD for the remainder of chromosome 1q (at 1q43-qter). In distal 1q duplication/triplication overlapping with 1q42.12-q43, variable clinical features have been reported, and our 25-year-old patient with MCA/ID presented with some of these frequently described features. Further analyses including the precise mapping of breakpoint junctions within the CGR in a sequence level suggested that the CGR found in association with isoUPD in our case is a triplication with flanking duplications, characterized as a triplication with a particularly long duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure. Because microhomology was observed in both junctions between the triplicated region and the flanking duplicated regions, our case provides supportive evidence for recently proposed replication-based mechanisms, such as MMBIR, underlying the formation of CGRs + isoUPD implicated in chromosomal disorders. To the best of our knowledge, this is the first case of CGRs + isoUPD observed in 1q and having DUP-TRP/INV-DUP structure with a long proximal duplication, which supports MMBIR-based model for genomic rearrangements. Molecular cytogenetic analyses using CMA containing single

Prevalence of rearrangements in the 22q11.2 region and population-based risk of neuropsychiatric and developmental disorders in a Danish population

DEFF Research Database (Denmark)

Olsen, Line; Sparsø, Thomas; Weinsheimer, Shantel M

2018-01-01

BACKGROUND: Although the pathogenic nature of copy number variants (CNVs) on chromosome 22q11.2 has been recognised for decades, unbiased estimates of their population prevalence, mortality, disease risks, and diagnostic trajectories are absent. We aimed to provide the true population prevalence ...

Familial DiGeorge/velocardiofacial syndrome with deletions of chromosome area 22q11.2: Report of five families with a review of the literature

Energy Technology Data Exchange (ETDEWEB)

Leana-Cox, J.; Pangkanon, Suthipong; Eanet, K.R. [Univ. of Maryland School of Medicine, Baltimore, MD (United States)] [and others

1996-11-11

The DiGeorge (DG), velocardiofacial (VCF), and conotruncal anomaly-face (CTAF) syndromes were originally described as distinct disorders, although overlapping phenotypes have been recognized. It is now clear that all three syndromes result from apparently similar or identical 22q11.2 deletions, suggesting that they represent phenotypic variability of a single genetic syndrome. We report on 12 individuals in five families with del(22)(q11.2) by fluorescent in situ hybridization, and define the frequency of phenotypic abnormalities in those cases and in 70 individuals from 27 del(22)(q11.2) families from the literature. Common manifestations include mental impairment (97%), abnormal face (93%), cardiac malformations (681%), thymic (64%) and parathyroid (63%) abnormalities, and cleft palate or velopharyngeal insufficiency (48%). Familial DG, VCF, and CTAF syndromes due to del(22)(q11.2) show significant inter- and intrafamilial clinical variability consistent with the hypothesis that a single gene or group of tightly linked genes is the common cause of these syndromes. Up to 25% of 22q deletions are inherited, indicating that parents of affected children warrant molecular cytogenetic evaluation. We propose use of the compound term {open_quotes}DiGeorge/velocardiofacial (DGNCF) syndrome{close_quotes} in referring to this condition, as it calls attention to the phenotypic spectrum using historically familiar names. 41 refs., 2 figs., 2 tabs.

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.

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

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

OpenAIRE

Yasutaka Tastuzawa; Kanako Sekinaka; Tetsufumi Suda; Hiroshi Matsumoto; Hiroyuki Otabe; Shigeaki Nonoyama; Aihide Yoshino

2015-01-01

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 ps...

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.

Partial deletion 11q

DEFF Research Database (Denmark)

Hertz, Jens Michael; Tommerup, N; Sørensen, F B

1995-01-01

We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most...

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.

Development of a 22q11DS psycho-educational programme: exploration of the views, concerns and educational needs of parents caring for children or adolescents with 22q11DS in relation to mental health issues.

Science.gov (United States)

Alugo, T; Malone, H; Sheehan, A; Coyne, I; Lawlor, A; McNicholas, F

2017-07-01

22q11.2 deletion syndrome (22q11DS) is a multisystem genetic condition with a broad phenotype. It is associated with a high prevalence of depression and anxiety during childhood and increased risk of schizophrenia in adulthood. Despite this, studies report that families may receive inadequate information of mental health (MH) risks at diagnosis. Therefore, this study investigated parents' experiences of caring for a child with 22q11DS, investigated their knowledge regarding the risk of MH problems and assessed the need for a psycho-educational programme. A qualitative design and purposeful sampling was utilized. Parents registered with the '22q11 Ireland' support group, and parents listed on the cleft palate database in a children's hospital in Ireland were invited to participate. Focus groups were held with 22 parents. Data were thematically analysed using Burnard's method of analysis. Most parents had some knowledge of the relationship between 22q11DS and an increased risk of MH issues. Parents reported that MH information relating to 22q11DS was mainly obtained from 22q11DS conferences, the '22q11 Ireland' support group and the Internet. Parents expressed a need for information to prevent or cope with their child's MH issues. Parents suggested that the following topics would be quite useful in a psycho-educational programme. These included information on the early warning signs of MH issues and guidance on when and how to tell the child about the condition and how to manage the child or young person's anxiety, obsessive behaviour or hearing voices. The findings indicated parental support for a psycho-educational programme that would provide relevant, accurate and timely information on how to effectively care for a child with 22q11DS MH needs. © 2017 John Wiley & Sons Ltd.

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.

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

Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome

NARCIS (Netherlands)

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.; 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

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

Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional connectivity analysis.

Science.gov (United States)

Mattiaccio, Leah M; Coman, Ioana L; Thompson, Carlie A; Fremont, Wanda P; Antshel, Kevin M; Kates, Wendy R

2018-01-20

22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental syndrome associated with deficits in cognitive and emotional processing. This syndrome represents one of the highest risk factors for the development of schizophrenia. Previous studies of functional connectivity (FC) in 22q11DS report aberrant connectivity patterns in large-scale networks that are associated with the development of psychotic symptoms. In this study, we performed a functional connectivity analysis using the CONN toolbox to test for differential connectivity patterns between 54 individuals with 22q11DS and 30 healthy controls, between the ages of 17-25 years old. We mapped resting-state fMRI data onto 68 atlas-based regions of interest (ROIs) generated by the Desikan-Killany atlas in FreeSurfer, resulting in 2278 ROI-to-ROI connections for which we determined total linear temporal associations between each. Within the group with 22q11DS only, we further tested the association between prodromal symptoms of psychosis and FC. We observed that relative to controls, individuals with 22q11DS displayed increased FC in lobar networks involving the frontal-frontal, frontal-parietal, and frontal-occipital ROIs. In contrast, FC between ROIs in the parietal-temporal and occipital lobes was reduced in the 22q11DS group relative to healthy controls. Moreover, positive psychotic symptoms were positively associated with increased functional connections between the left precuneus and right superior frontal gyrus, as well as reduced functional connectivity between the bilateral pericalcarine. Positive symptoms were negatively associated with increased functional connectivity between the right pericalcarine and right postcentral gyrus. Our results suggest that functional organization may be altered in 22q11DS, leading to disruption in connectivity between frontal and other lobar substructures, and potentially increasing risk for prodromal psychosis.

Association study of candidate genes for susceptibility to schizophrenia and bipolar disorder on chromosome 22Q13

DEFF Research Database (Denmark)

Severinsen, Jacob; Binderup, Helle; Mors, Ole

Chromosome 22q is suspected to harbor risk genes for schizophrenia as well as bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. In a recent study of distantly related patients from...... the Faroe Islands we have obtained evidence suggesting two regions on chromosome 22q13 to potentially harbor susceptibility genes for both schizophrenia and bipolar affective disorder. We have selected a number of candidate genes from these two regions for further analysis, including the neuro-gene WKL1...... and unrelated controls, and in a Scottish case-control sample comprising 200 schizophrenics, 200 bipolar patients and 200 controls. None of the investigated SNPs have so far showed strong evidence of association to either bipolar disorder or schizophrenia....

Graves disease and IgA deficiency as manifestations of 22q11.2 deletion syndrome:

OpenAIRE

Silva, João Miguel de Almeida; Silva, Cecília Pereira; Melo, Flavio Fernando Nogueira de; Silva, Luis Alberto A.; Utagawa, Claudia Yamada

2010-01-01

A síndrome de deleção 22q11.2 (SD22q11.2) está associada à alta variabilidade fenotípica, abrangendo o espectro velocardiofacial/síndrome de DiGeorge. Manifestações autoimunes, endocrinológicas e de imunodeficiência vêm sendo relatadas associadas à síndrome. O objetivo deste estudo foi relatar um caso de SD22q11.2 associado à deficiência de IgA e à doença de Graves e rever a literatura visando verificar a frequência dessas alterações na SD22q11.2. Os distúrbios autoimunes, cada vez mais relac...

Syntenic homology of human unique DNA sequences within chromossome regions 5q31, 10q22, 13q32-33 and 19q13.1 in the great apes

Directory of Open Access Journals (Sweden)

Rhea U. Vallente-Samonte

2000-09-01

Full Text Available Homologies between chromosome banding patterns and DNA sequences in the great apes and humans suggest an apparent common origin for these two lineages. The availability of DNA probes for specific regions of human chromosomes (5q31, 10q22, 13q32-33 and 19q13.1 led us to cross-hybridize these to chimpanzee (Pan troglodytes, PTR, gorilla (Gorilla gorilla, GGO and orangutan (Pongo pygmaeus, PPY chromosomes in a search for equivalent regions in the great apes. Positive hybridization signals to the chromosome 5q31-specific DNA probe were observed at HSA 5q31, PTR 4q31, GGO 4q31 and PPY 4q31, while fluorescent signals using the chromosome 10q22-specific DNA probe were noted at HSA 10q22, PTR 8q22, GGO 8q22 and PPY 7q22. The chromosome arms showing hybridization signals to the Quint-EssentialTM 13-specific DNA probe were identified as HSA 13q32-33, PTR 14q32-33, GGO 14q32-33 and PPY 14q32-33, while those presenting hybridization signals to the chromosome 19q13.1-specific DNA probe were identified as HSA 19q13.1, PTR 20q13, GGO 20q13 and PPY 20q13. All four probes presumably hybridized to homologous chromosomal locations in the apes, which suggests a homology of certain unique DNA sequences among hominoid species.Homologias entre os padrões de bandamento de cromossomos e seqüências de DNA em grandes macacos e humanos sugerem uma aparente origem comum para estas duas linhagens. A disponibilidade de sondas de DNA para regiões específicas de cromossomos humanos (5q31, 10q22, 13q32-33 e 19q13.1 nos levou a realizar hibridação cruzada com cromossomos de chimpanzé (Pan troglodytes, PTR, gorila (Gorilla gorilla, GGO e orangotango (Pongo pygmaeus, PPY em um pesquisa de regiões equivalentes em grandes macacos. Sinais positivos de hibridação para a sonda de DNA específica para o cromossomo 5q31 foram observados em HSA 5q31, PTR 4q31, GGO 4q31 e PPY 4q31, enquanto que sinais fluorescentes usando a sonda de DNA específica para o cromossomo 10q22 foram

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.

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.

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.

The presence of two rare genomic syndromes, 1q21 deletion and Xq28 duplication, segregating independently in a family with intellectual disability.

Science.gov (United States)

Ha, Kyungsoo; Shen, Yiping; Graves, Tyler; Kim, Cheol-Hee; Kim, Hyung-Goo

2016-01-01

1q21 microdeletion syndrome is a rare contiguous gene deletion disorder with de novo or autosomal dominant inheritance patterns and its phenotypic features include intellectual disability, distinctive facial dysmorphism, microcephaly, cardiac abnormalities, and cataracts. MECP2 duplication syndrome is an X-linked recessive neurodevelopmental disorder characterized by intellectual disability, global developmental delay, and other neurological complications including late-onset seizures. Previously, these two different genetic syndromes have not been reported segregating independently in a same family. Here we describe two siblings carrying either a chromosome 1q21 microdeletion or a chromosome Xq28 duplication. Using a comparative genomic hybridization (CGH) array, we identified a 1.24 Mb heterozygous deletion at 1q21 resulting in the loss of 9 genes in a girl with learning disability, hypothyroidism, short stature, sensory integration disorder, and soft dysmorphic features including cupped ears and a unilateral ear pit. We also characterized a 508 kb Xq28 duplication encompassing MECP2 in her younger brother with hypotonia, poor speech, cognitive and motor impairment. The parental CGH and quantitative PCR (qPCR) analyses revealed that the 1q21 deletion in the elder sister is de novo , but the Xq28 duplication in the younger brother was originally inherited from the maternal grandmother through the mother, both of whom are asymptomatic carriers. RT-qPCR assays revealed that the affected brother has almost double the amount of MECP2 mRNA expression compared to other family members of both genders including maternal grandmother and mother who have the same Xq28 duplication with no phenotype. This suggests the X chromosome with an Xq28 duplication in the carrier females is preferentially silenced. From our understanding, this would be the first report showing the independent segregation of two genetically unrelated syndromes, 1q21 microdeletion and Xq28 duplication

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…

Deletion 22q13.3 syndrome

Directory of Open Access Journals (Sweden)

Phelan Mary C

2008-05-01

Full Text Available Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH or array comparative genomic hybridization (CGH is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy. Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements

Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain.

Science.gov (United States)

Harper, Kathryn M; Hiramoto, Takeshi; Tanigaki, Kenji; Kang, Gina; Suzuki, Go; Trimble, William; Hiroi, Noboru

2012-08-01

Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception-and their genetic underpinnings-are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene.

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

Brief Report: Functional MRI of a Patient with 7q11.23 Duplication Syndrome and Autism Spectrum Disorder

Science.gov (United States)

Prontera, Paolo; Serino, Domenico; Caldini, Bernardo; Scarponi, Laura; Merla, Giuseppe; Testa, Giuseppe; Muti, Marco; Napolioni, Valerio; Mazzotta, Giovanni; Piccirilli, Massimo; Donti, Emilio

2014-01-01

The duplication of the Williams-Beuren syndrome (WBS) region (7q11.23) is a copy number variant associated with autism spectrum disorder (ASD). One of the most intriguing aspects is that the reciprocal microdeletion causes WBS, characterized by hypersociability, marked empathy, and a relative capacity in verbal short-term memory and language.…

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12.

Science.gov (United States)

Nagamani, Sandesh Chakravarthy Sreenath; Erez, Ayelet; Shen, Joseph; Li, Chumei; Roeder, Elizabeth; Cox, Sarah; Karaviti, Lefkothea; Pearson, Margret; Kang, Sung-Hae L; Sahoo, Trilochan; Lalani, Seema R; Stankiewicz, Pawel; Sutton, V Reid; Cheung, Sau Wai

2010-03-01

Deletions in chromosome 17q12 encompassing the HNF1 beta gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with an increased risk of epilepsy and mental retardation. We conducted a detailed clinical and molecular characterization of four patients with a deletion and five patients with a reciprocal duplication of this region. Our patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioral abnormalities, but not with seizures. Our findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.

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

Science.gov (United States)

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…

Abordaje inmunológico del síndrome por deleción 22q11

Directory of Open Access Journals (Sweden)

Estefanía Vásquez-Echeverri

Full Text Available El síndrome por deleción 22q11 (SD22q11 es el síndrome por deleción cromosómica más frecuente en humanos y se caracteriza por la tríada clínica que incluye cardiopatía congénita, hipocalcemia e inmunodeficiencia primaria. El 85-90% de los pacientes tienen microdeleciones en el cromosoma 22q11.2. Tomando como punto cardinal la cardiopatía congénita, se diseñó una estrategia para tamización y diagnóstico de SD22q11 con énfasis en la evaluación inmune. Es imprescindible realizar una historia clínica detallada y, posteriormente, un análisis cuantitativo y funcional de las subpoblaciones de linfocitos en sangre periférica para clasificarlo en SD22q11 completo (<1% o parcial (95-99% e instaurar las pautas de tratamiento en aspectos como: aislamiento del paciente, vacunación, profilaxis contra microorganismos oportunistas, uso de productos sanguíneos irradiados y reconstitución inmunológica. Sin embargo, el abordaje del paciente debe ser multidisciplinario para detectar y prevenir complicaciones a largo plazo que pueden ser graves, especialmente en los pacientes con SD22q11 completo.

Severe intellectual disability, omphalocele, hypospadia and high blood pressure associated to a deletion at 2q22.1q22.3: case report

Directory of Open Access Journals (Sweden)

Mulatinho Milene

2012-06-01

Full Text Available Abstract Background Recently, array-comparative genomic hybridization (aCGH platforms have significantly improved the resolution of chromosomal analysis allowing the identification of genomic copy number gains and losses smaller than 5 Mb. Here we report on a young man with unexplained severe mental retardation, autism spectrum disorder, congenital malformations comprising hypospadia and omphalocele, and episodes of high blood pressure. An ~ 6 Mb interstitial deletion that includes the causative genes is identified by oligonucleotide-based aCGH. Results Our index case exhibited a de novo chromosomal abnormality at 2q22 [del(2(q22.1q22.3dn] which was not visible at the 550 haploid band level. The deleted region includes eight genes: HNMT, SPOPL, NXPH2, LOC64702, LRP1B, KYNU, ARHGAP15 and GTDC1. Discussion aCGH revealed an ~ 6 Mb deletion in 2q22.1 to 2q22.3 in an as-yet unique clinical case associated with intellectual disability, congenital malformations and autism spectrum disorder. Interestingly, the deletion is co-localized with a fragile site (FRA2K, which could be involved in the formation of this chromosomal aberration. Further studies are needed to determine if deletions of 2q22.1 to 2q22.3 define a new microdeletion syndrome.

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.

Biparental inheritance of chromosomal abnormalities in male twins with non-syndromic mental retardation

DEFF Research Database (Denmark)

Nielsen, Mette Gilling; Lind-Thomsen, Allan; Mang, Yuan

2011-01-01

In a monozygotic twin couple with mental retardation (MR), we identified a maternally inherited inversion and a paternally inherited translocation: 46,XY,inv(10)(p11.2q21.2)mat,t(9;18)(p22;q21.1)pat. The maternally inherited inv(10) was a benign variant without any apparent phenotypical...... implications. The translocation breakpoint at 9p was within a cluster of interferon a genes and the 18q21 breakpoint truncated ZBTB7C (zinc finger and BTB containing 7C gene). In addition, analyses with array-CGH revealed a 931 kb maternally inherited deletion on chromosome 8q22 as well as an 875 kb maternally...... inherited duplication on 5p14. The deletion encompasses the RIM2 (Rab3A-interacting molecule 2), FZD6 (Frizzled homolog 6) and BAALC (Brain and Acute Leukemia Gene, Cytoplasmic) genes and the duplication includes the 5' end of the CDH9 (cadherin 9) gene. Exome sequencing did not reveal any additional...

Cortical Development Requires Mesodermal Expression of Tbx1, a Gene Haploinsufficient in 22q11.2 Deletion Syndrome.

Science.gov (United States)

Flore, Gemma; Cioffi, Sara; Bilio, Marchesa; Illingworth, Elizabeth

2017-03-01

In mammals, proper temporal control of neurogenesis and neural migration during embryonic development ensures correct formation of the cerebral cortex. Changes in the distribution of cortical projection neurons and interneurons are associated with behavioral disorders and psychiatric diseases, including schizophrenia and autism, suggesting that disrupted cortical connectivity contributes to the brain pathology. TBX1 is the major candidate gene for 22q11.2 deletion syndrome (22q11.2DS), a chromosomal deletion disorder characterized by a greatly increased risk for schizophrenia. We have previously shown that Tbx1 heterozygous mice have reduced prepulse inhibition, a behavioral abnormality that is associated with 22q11.2DS and nonsyndromic schizophrenia. Here, we show that loss of Tbx1 disrupts corticogenesis in mice by promoting premature neuronal differentiation in the medio-lateral embryonic cortex, which gives rise to the somatosensory cortex (S1). In addition, we found altered polarity in both radially migrating excitatory neurons and tangentially migrating inhibitory interneurons. Together, these abnormalities lead to altered lamination in the S1 at the terminal stages of corticogenesis in Tbx1 null mice and similar anomalies in Tbx1 heterozygous adult mice. Finally, we show that mesoderm-specific inactivation of Tbx1 is sufficient to recapitulate the brain phenotype indicating that Tbx1 exerts a cell nonautonomous role in cortical development from the mesoderm. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tetrasomy 15q11-q13 identified by fluorescence in situ hybridization in a patient with autistic disorder Identificação de tetrassomia 15q11-q13 por hibridação in situ fluorescente em uma paciente com distúrbio autístico

Directory of Open Access Journals (Sweden)

Ana Elizabete Silva

2002-06-01

Full Text Available We report a female child with tetrasomy of the 15q11-q13 chromosomal region, and autistic disorder associated with mental retardation, developmental problems and behavioral disorders. Combining classical and molecular cytogenetic approaches by fluorescence in situ hybridization technique, the karyotype was demonstrated as 47,XX,+mar.ish der(15(D15Z1++,D15S11++,GABRB3++,PML-. Duplication of the 15q proximal segment represents the most consistent chromosomal abnormality reported in association with autism. The contribution of the GABA receptor subunit genes, and other genes mapped to this region, to the clinical symptoms of the disease is discussed.Relatamos uma criança do sexo feminino com tetrassomia da região cromossômica 15q11-q13 e distúrbio autístico associado com retardo mental, problemas de desenvolvimento e distúrbios comportamentais. A combinação de metodologias da citogenética clássica e molecular pela técnica de hibridação in situ fluorescente, demonstrou o cariótipo como 47,XX,+mar.ish der(15 (D15Z1++,D15S11++,GABRB3++,PML. Duplicação do segmento 15q proximal representa a mais consistente anomalia cromossômica relatada em associação com autismo. A contribuição dos genes das subunidades do recepetor GABA, assim como outros genes mapeados nessa região, para os sintomas clínicos da doença é discutida.

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…

Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe Islands

DEFF Research Database (Denmark)

Jorgensen, Tove H; Børglum, A.D; Mors, O

2002-01-01

Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe...... was found at a segment of at least 1.1 cM including markers D22S1161 and D22S922 (P=0.0081 in the test for association). Our results also support the a priori evidence of a susceptibility gene to schizophrenia at a segment of at least 0.45 cM including markers D22S279 and D22S276 (P=0.0075). Patients were...... tested for the presence of a missense mutation in the WKL1 gene encoding a putative cation channel close to segment D22S1161-D22S922, which has been associated with schizophrenia. We did not find this mutation in schizophrenic or bipolar patients or the controls from the Faroe Islands. © 2002 Wiley...

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

A rare duplication on chromosome 16p11.2 is identified in patients with psychosis in Alzheimer's disease.

Directory of Open Access Journals (Sweden)

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.

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.

Inversion duplication deletions involving the long arm of chromosome 13: phenotypic description of additional three fetuses and genotype-phenotype correlation.

Science.gov (United States)

Quelin, Chloe; Spaggiari, Emmanuel; Khung-Savatovsky, Suonavy; Dupont, Celine; Pasquier, Laurent; Loeuillet, Laurence; Jaillard, Sylvie; Lucas, Josette; Marcorelles, Pascale; Journel, Hubert; Pluquailec-Bilavarn, Khantaby; Bazin, Anne; Verloes, Alain; Delezoide, Anne-Lise; Aboura, Azzedine; Guimiot, Fabien

2014-10-01

Inversion duplication and terminal deletion of the long arm of chromosome 13 (inv dup del 13q) is a rare chromosomal rearrangement: only five patients have been reported, mostly involving a ring chromosome 13. We report on additional three fetuses with pure inv dup del 13q: Patient 1 had macrosomia, enlarged kidneys, hypersegmented lungs, unilateral moderate ventriculomegaly, and a mild form of hand and feet preaxial polydactyly; Patient 2 had intrauterine growth retardation, widely spaced eyes, left microphthalmia, right anophthalmia, short nose, bilateral absent thumbs, cutaneous syndactyly of toes 4 and 5, bifid third metacarpal, a small left kidney, hyposegmented lungs, and partial agenesis of the corpus callosum; Patient 3 had widely spaced eyes, long and smooth philtrum, low-set ears, median notch in the upper alveolar ridge, bifid tongue, cutaneous syndactyly of toes 2 and 3, enlarged kidneys and pancreas, arhinencephaly, and partial agenesis of the corpus callosum. We compared the phenotypes of these patients to those previously reported for ring chromosome 13, pure 13q deletions and duplications. We narrowed some critical regions previously reported for lung, kidney and fetal growth, and for thumb, cerebral, and eye anomalies. © 2014 Wiley Periodicals, Inc.

Microarray Analysis of Copy Number Variants on the Human Y Chromosome Reveals Novel and Frequent Duplications Overrepresented in Specific Haplogroups.

Directory of Open Access Journals (Sweden)

Martin M Johansson

Full Text Available The human Y chromosome is almost always excluded from genome-wide investigations of copy number variants (CNVs due to its highly repetitive structure. This chromosome should not be forgotten, not only for its well-known relevance in male fertility, but also for its involvement in clinical phenotypes such as cancers, heart failure and sex specific effects on brain and behaviour.We analysed Y chromosome data from Affymetrix 6.0 SNP arrays and found that the signal intensities for most of 8179 SNP/CN probes in the male specific region (MSY discriminated between a male, background signals in a female and an isodicentric male containing a large deletion of the q-arm and a duplication of the p-arm of the Y chromosome. Therefore, this SNP/CN platform is suitable for identification of gain and loss of Y chromosome sequences. In a set of 1718 males, we found 25 different CNV patterns, many of which are novel. We confirmed some of these variants by PCR or qPCR. The total frequency of individuals with CNVs was 14.7%, including 9.5% with duplications, 4.5% with deletions and 0.7% exhibiting both. Hence, a novel observation is that the frequency of duplications was more than twice the frequency of deletions. Another striking result was that 10 of the 25 detected variants were significantly overrepresented in one or more haplogroups, demonstrating the importance to control for haplogroups in genome-wide investigations to avoid stratification. NO-M214(xM175 individuals presented the highest percentage (95% of CNVs. If they were not counted, 12.4% of the rest included CNVs, and the difference between duplications (8.9% and deletions (2.8% was even larger.Our results demonstrate that currently available genome-wide SNP platforms can be used to identify duplications and deletions in the human Y chromosome. Future association studies of the full spectrum of Y chromosome variants will demonstrate the potential involvement of gain or loss of Y chromosome sequence in

Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

Science.gov (United States)

Cheung, Evelyn Ning Man; George, Susan R.; Andrade, Danielle M.; Chow, Eva W. C.; Silversides, Candice K.; Bassett, Anne S.

2015-01-01

Purpose Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome. Methods We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability. Results The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate- to-severe intellectual disability with other factors such as major structural brain malformations in this sample. Conclusion The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions. PMID:23765047

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...

A novel 5p15.33-14.1 deletion and 4q34.24-35.2 duplication in a ...

Indian Academy of Sciences (India)

Both are normal in phenotype and intelligence. His mother ... Bacterial artificial chromosome (BAC) clone RP11-159A22. (4q35.1) was ... However, we can not exclude the impacts ... researchers of State Key Laboratory of Medical Genetics.

Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 or r(8(::p12→q13.1:: associated with phenotypic abnormalities

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2016-12-01

Conclusion: Mosaic sSMC(8 derived from r(8(::p12→q13.1:: can present phenotypic abnormalities. Chromosome 8q12 duplication syndrome should be included in differential diagnosis when an sSMC(8 contains 8q12.2 and CHD7.

Children with 7q11.23 Duplication Syndrome: Psychological Characteristics

Science.gov (United States)

Mervis, Carolyn B.; Klein-Tasman, Bonita P.; Huffman, Myra J.; Velleman, Shelley L.; Pitts, C. Holley; Henderson, Danielle R.; Woodruff-Borden, Janet; Morris, Colleen A.; Osborne, Lucy R.

2015-01-01

To begin to delineate the psychological characteristics associated with classic 7q11.23 duplication syndrome (duplication of the classic Williams syndrome region; hereafter classic Dup7), we tested 63 children with classic Dup7 aged 4–17 years. Sixteen toddlers aged 18–45 months with classic Dup7 and 12 adults identified by cascade testing also were assessed. For the child group, median General Conceptual Ability (similar to IQ) on the Differential Ability Scales-II was 85.0 (low average), with a range from severe disability to high average ability. Median reading and mathematics achievement standard scores were at the low average to average level, with a range from severe impairment to high average or superior ability. Adaptive behavior was considerably more limited; median Scales of Independent Behavior—Revised Broad Independence standard score was 62.0 (mild impairment), with a range from severe adaptive impairment to average adaptive ability. Anxiety disorders were common, with 50.0% of children diagnosed with Social Phobia, 29.0% with Selective Mutism, 12.9% with Separation Anxiety Disorder, and 53.2% with Specific Phobia. In addition, 35.5% were diagnosed with Attention Deficit/Hyperactivity Disorder and 24.2% with Oppositional Defiant Disorder or Disruptive Behavior Disorder-Not Otherwise Specified. 33.3% of the children screened positive for a possible Autism Spectrum Disorder and 82.3% were diagnosed with Speech Sound Disorder. We compare these findings to previously reported results for children with Williams syndrome and argue that genotype/phenotype studies involving the Williams syndrome region offer important opportunities to understand the contribution of genes in this region to common disorders affecting the general population. PMID:25900101

Children with 7q11.23 duplication syndrome: psychological characteristics.

Science.gov (United States)

Mervis, Carolyn B; Klein-Tasman, Bonita P; Huffman, Myra J; Velleman, Shelley L; Pitts, C Holley; Henderson, Danielle R; Woodruff-Borden, Janet; Morris, Colleen A; Osborne, Lucy R

2015-07-01

To begin to delineate the psychological characteristics associated with classic 7q11.23 duplication syndrome (duplication of the classic Williams syndrome region; hereafter classic Dup7), we tested 63 children with classic Dup7 aged 4-17 years. Sixteen toddlers aged 18-45 months with classic Dup7 and 12 adults identified by cascade testing also were assessed. For the child group, median General Conceptual Ability (similar to IQ) on the Differential Ability Scales-II was 85.0 (low average), with a range from severe disability to high average ability. Median reading and mathematics achievement standard scores were at the low average to average level, with a range from severe impairment to high average or superior ability. Adaptive behavior was considerably more limited; median Scales of Independent Behavior-Revised Broad Independence standard score was 62.0 (mild impairment), with a range from severe adaptive impairment to average adaptive ability. Anxiety disorders were common, with 50.0% of children diagnosed with Social Phobia, 29.0% with Selective Mutism, 12.9% with Separation Anxiety Disorder, and 53.2% with Specific Phobia. In addition, 35.5% were diagnosed with Attention Deficit/Hyperactivity Disorder and 24.2% with Oppositional Defiant Disorder or Disruptive Behavior Disorder-Not Otherwise Specified. 33.3% of the children screened positive for a possible Autism Spectrum Disorder and 82.3% were diagnosed with Speech Sound Disorder. We compare these findings to previously reported results for children with Williams syndrome and argue that genotype/phenotype studies involving the Williams syndrome region offer important opportunities to understand the contribution of genes in this region to common disorders affecting the general population. © 2015 Wiley Periodicals, Inc.

Maternally Derived Microduplications at 15q11-q13: Implication of Imprinted Genes in Psychotic Illness

DEFF Research Database (Denmark)

Ingason, Andrés; Kirov, George; Giegling, Ina

2011-01-01

or schizoaffective disorder and 41,370 comparison subjects without known psychiatric illness for copy number variants at 15q11-q13 and determined the parental origin of duplications using methylation-sensitive Southern hybridization analysis. Results: Duplications were found in four case patients and five comparison...

A Novel 2.3 Mb Microduplication of 9q34.3 Inserted into 19q13.4 in a Patient with Learning Disabilities

Directory of Open Access Journals (Sweden)

Shalinder Singh

2012-01-01

Full Text Available Insertional translocations in which a duplicated region of one chromosome is inserted into another chromosome are very rare. We report a 16.5-year-old girl with a terminal duplication at 9q34.3 of paternal origin inserted into 19q13.4. Chromosomal analysis revealed the karyotype 46,XX,der(19ins(19;9(q13.4;q34.3q34.3pat. Cytogenetic microarray analysis (CMA identified a ~2.3Mb duplication of 9q, which was confirmed by Fluorescence in situ hybridisation (FISH. The duplication at 9q34.3 is the smallest among the cases reported so far. The proband exhibits similar clinical features to those previously reported cases with larger duplication events.

Malformation/dysplasia syndrome (neural tube defect, hypospadias neuroblastoma) associated with an extra dicentric marker chromosome 15 ({open_quotes}inversion duplication 15{close_quotes})

Energy Technology Data Exchange (ETDEWEB)

Reitnauer, P.J.; Rao, K.W.; Tepperberg, J.H. [Univ. of North Carolina, Chapel Hill, NC (United States)

1994-09-01

Extra dicentric 15 marker chromosomes are associated with variable degrees of mental retardation but not major structural birth defects. We have studied a unique patient, a male infant who was prenatally diagnosed with lumbar meningomyelocele and an extra pseudodicentric marker chromosome: 47,XY,+psu dic(15)t(15;15)(?q12,?q12)mat. Hairy ears and a coronal hypospadias were noted at birth. At three months of age, a stage I thoracic neuroblastoma was primarily resected. Tumor cells, skin fibroblasts and peripheral blood lymphocytes contained the dicentric 15. The mother is mosaic for the marker chromosome. Fluorescence in situ hybridization (FISH) studies using a classic 15 satellite probe (D15Z1 [Oncor]) confirmed the presence of 2 number 15 centromeres in the marker. The marker is felt to be the result of a translocation rather than an inverted duplication because the G-band morphology of the short arm/satellite complexes differ from one another, implying that the arms originate from 2 different number 15s. FISH analysis using cosmid probes for the Prader-Willi/Angelman critical region (D15S11 and GABRB3 [Oncor]) revealed 2 copies of this region, indicating that these loci are duplicated in the marker. Although some features of the patient`s phenotype such as developmental delay and hypotonia have been associated with dicentric chromosome 15 markers, this is the first malformation/dysplasia syndrome or neuroblastoma reported to our knowledge. The association of neuroblastoma with chromosome 15 aberrations in this case provides speculation as to the role of chromosome 15 loci in cell division control.

Chromosome 15q24 microdeletion syndrome

Directory of Open Access Journals (Sweden)

Magoulas Pilar L

2012-01-01

involves a multi-disciplinary approach to care with the primary care physician and clinical geneticist playing a crucial role in providing appropriate screening, surveillance, and care for individuals with this syndrome. At the time of diagnosis, individuals should receive baseline echocardiograms, audiologic, ophthalmologic, and developmental assessments. Growth and feeding should be closely monitored. Other specialists that may be involved in the care of individuals with 15q24 deletion syndrome include immunology, endocrine, orthopedics, neurology, and urology. Chromosome 15q24 microdeletion syndrome should be differentiated from other genetic syndromes, particularly velo-cardio-facial syndrome (22q11.2 deletion syndrome, Prader-Willi syndrome, and Noonan syndrome. These conditions share some phenotypic similarity to 15q24 deletion syndrome yet have characteristic features specific to each of them that allows the clinician to distinguish between them. Molecular genetic testing and/or aCGH will be able to diagnose these conditions in the majority of individuals. Disease name and synonyms Chromosome 15q24 deletion syndrome 15q24 deletion syndrome 15q24 microdeletion syndrome

TBX1 mutation identified by exome sequencing in a Japanese family with 22q11.2 deletion syndrome-like craniofacial features and hypocalcemia.

Directory of Open Access Journals (Sweden)

Tsutomu Ogata

Full Text Available BACKGROUND: Although TBX1 mutations have been identified in patients with 22q11.2 deletion syndrome (22q11.2DS-like phenotypes including characteristic craniofacial features, cardiovascular anomalies, hypoparathyroidism, and thymic hypoplasia, the frequency of TBX1 mutations remains rare in deletion-negative patients. Thus, it would be reasonable to perform a comprehensive genetic analysis in deletion-negative patients with 22q11.2DS-like phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: We studied three subjects with craniofacial features and hypocalcemia (group 1, two subjects with craniofacial features alone (group 2, and three subjects with normal phenotype within a single Japanese family. Fluorescence in situ hybridization analysis excluded chromosome 22q11.2 deletion, and genomewide array comparative genomic hybridization analysis revealed no copy number change specific to group 1 or groups 1+2. However, exome sequencing identified a heterozygous TBX1 frameshift mutation (c.1253delA, p.Y418fsX459 specific to groups 1+2, as well as six missense variants and two in-frame microdeletions specific to groups 1+2 and two missense variants specific to group 1. The TBX1 mutation resided at exon 9C and was predicted to produce a non-functional truncated protein missing the nuclear localization signal and most of the transactivation domain. CONCLUSIONS/SIGNIFICANCE: Clinical features in groups 1+2 are well explained by the TBX1 mutation, while the clinical effects of the remaining variants are largely unknown. Thus, the results exemplify the usefulness of exome sequencing in the identification of disease-causing mutations in familial disorders. Furthermore, the results, in conjunction with the previous data, imply that TBX1 isoform C is the biologically essential variant and that TBX1 mutations are associated with a wide phenotypic spectrum, including most of 22q11.2DS phenotypes.

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors

International Nuclear Information System (INIS)

Bystroem, C.; Larsson, C.; Blomberg, C.; Nordenskjoeld, M.; Sandelin, K.; Falkmer, U.; Werner, S.; Skogseid, B.; Oeberg, K.

1990-01-01

The gene for multiple endocrine neoplasia type 1 (MEN1), and inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. The authors now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, they could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas

Translocation t(11;14 (q13;q32 and genomic imbalances in multi-ethnic multiple myeloma patients: a Malaysian study

Directory of Open Access Journals (Sweden)

Ivyna Bong Pau Ni

2012-09-01

Full Text Available More than 50% of myeloma cases have normal karyotypes under conventional cytogenetic analysis due to low mitotic activity and content of plasma cells in the bone marrow. We used a polymerase chain reaction (PCR-based translocation detection assay to detect BCL1/JH t(11;14 (q13;q32 in 105 myeloma patients, and randomly selected 8 translocation positive samples for array comparative genomic hybridization (aCGH analysis. Our findings revealed 14.3% of myeloma samples were positive for BCL1/JH t(11;14 (q13;q32 translocation (n=15 of 105. We found no significant correlation between this translocation with age (P=0.420, gender (P=0.317, ethnicity (P=0.066 or new/relapsed status of multiple myeloma (P=0.412 at 95% confidence interval level by x2 test. In addition, aCGH results showed genomic imbalances in all samples analyzed. Frequent chromosomal gains were identified at regions 1q, 2q, 3p, 3q, 4p, 4q, 5q, 7q, 9q, 11q, 13q, 15q, 21q, 22q and Xq, while chromosomal losses were detected at 4q and 14q. Copy number variations at genetic loci that contain NAMPT, IVNS1ABP and STK17B genes are new findings that have not previously been reported in myeloma patients. Besides fluorescence in situ hybridization, PCR is another rapid, sensitive and simple technique that can be used for detecting BCL1/JH t(11;14(q13;q32 translocation in multiple myeloma patients. Genes located in the chromosomal aberration regions in our study, such as NAMPT, IVNS1ABP, IRF2BP2, PICALM, STAT1, STK17B, FBXL5, ACSL1, LAMP2, SAMSN1 and ATP8B4 might be potential prognostic markers and therapeutic targets in the treatment and management of multiple myeloma patients positive for BCL1/JH t(11;14 (q13;q32 translocation.

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.

Verbal short-term memory in individuals with chromosome 22q11.2 deletion: Specific deficit in serial order retention capacities?

OpenAIRE

Majerus, Steve; Van der Linden, Martial; Braissand, V.; Eliez, S.

2007-01-01

Many researchers have recently explored the cognitive profile of velocardiofacial syndrome (VCFS), a neurodevelopmental disorder linked to a 22q11.2 deletion. However, verbal short-term memory has not yet been systematically investigated. We explored verbal short-term memory abilities in a group of 11 children and adults presenting with VCFS and two control groups, matched on either CA or vocabulary knowledge, by distinguishing short-term memory for serial order and item information. The VCFS...

De novo interstitial deletions of 9q22.1-22.3 in two unrelated cases with different phenotype

Energy Technology Data Exchange (ETDEWEB)

Mohamed, A.N.; Bawle, E.; Conard, J. [Wayne State Univ., Detroit, MI (United States)] [and others

1994-09-01

Deletions involving the long arm of chromosome 9 are rare. A recent review, particularly with deletions of 9q22-32 region, failed to recognize a distinct pattern of dysmorphies and malformations. Herein, we described two phenotypically abnormal unrelated cases with interstitial deletion of chromosome 9 at band q22.1-q22.3. Parents of both cases exhibited normal karyotypes, indicating that the deletions were de novo events. Therefore, the clinical features present in these two cases can be attributed to partial monosomy for the deleted band 9q22. The first case was a 2-day-old baby with ambiguous genitalia, hydrocephalus, cleft palate and lip, polycystic kidney, absence of uterus on ultrasound and one gonad in the labiosacral region. Chromosome analysis showed a male karyotype, 46,XY,del(9)(q22.1q22.3). The absence of monosomy X cell line and the normal histology of testicular tissue were against the diagnosis of mixed gonadal dysgenesis or XY gonadal dysgenesis. The second 3-day-old newborn baby girl presented with right side hypoplastic heart and pulmonary atresia. In addition, the patient showed multiple dysmorphic features including epicanthal fold, low-set ears, depressed nasal bridge, hypertelorism, and micrognathia. The uvula is absent with slight cleft palate. Bilateral clinodactyly of 5th fingers and severe club feet were also present. The external genitalia was of a normal female phenotype. Chromosome study also indicated interstatial deletion of band 9q22. Although both cases appeared to have the same chromosomal anomalies, neither a discrete facial appearance nor a common pattern of malformations was noted.

Isolation of anonymous, polymorphic DNA fragments from human chromosome 22q12-qter

NARCIS (Netherlands)

J.P. Dumanski (Jan); A.H.M. Geurts van Kessel (Ad); M. Ruttledge (Martin); A. Wladis (Andreas); N. Sugawa (Noriaki); V.P. Collins (Peter); M. Nordenskjöld

1990-01-01

textabstractA series of 195 random chromosome 22-specific probes, equivalent to approximately 1% of the size of this chromosome, have been isolated from a chromosome 22-specific bacteriophage lambda genomic library. These probes were mapped to four different regions of chromosome 22 on a panel of

Chromosome break points in T-lymphocytes from atomic bomb survivors

International Nuclear Information System (INIS)

Tanaka, Kimio; Kamada, Nanao; Ohkita, Takeshi; Kuramoto, Atsushi

1982-01-01

In 22 healthy A-bomb survivors who passed more than 30 years since receiving radiation, distribution of 592 chromosome break points found in T-lymphocytes of the peripheral blood was not proportional to the length, the arm length of chromosomes, nor the length of regions, but it was non-random on the chromosomes. High distribution of chromosome break points occurred in 11 regions: 22q1, 14q3, 5q3, 21q2, 6q2, 18p1, 13q3. The regions, 22q1, 14q3, 21q2, and 6q2, contained the chromosome break points which were frequently found in leukemic chromosomes. Some of the changes in nuclear-type observed in leukemic cells of A-bomb survivors were similar to those found in leukemic cells of non-exposed leukemic patients. In abnormal chromosomes of T-lymphocytes of healthy A-bomb survivors, no cells with abnormal nuclear types such as t(4;11), t(8;21), t(9;22), and t(15;17) which are seen in various types of leukemia were not found. However, cells with chromosome aberrations, 22q-, 14q+, and 6q-, were found to be 0.99%, 0.55%, and 0.25% respectively. On the basis of these results, implication of chromosome aberrations in developing cancer was discussed. (Ueda, J.)

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.

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

OpenAIRE

Nagamani, Sandesh Chakravarthy Sreenath; Erez, Ayelet; Shen, Joseph; Li, Chumei; Roeder, Elizabeth; Cox, Sarah; Karaviti, Lefkothea; Pearson, Margret; Kang, Sung-Hae L; Sahoo, Trilochan; Lalani, Seema R; Stankiewicz, Pawel; Sutton, V Reid; Cheung, Sau Wai

2009-01-01

Deletions in chromosome 17q12 encompassing the HNF1β gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with a...

Construction of radiation-reduced hybrids and their use in mapping of microclones from chromosome 10p11.2-q11.2

International Nuclear Information System (INIS)

Fujita, Shoichi; Shin, Eisei; Nakamura, Tsutomu; Kurahashi, Hiroki; Mori, Takesada; Takai, Shin-ichiro; Nishisho, Isamu; Kaneda, Yasufumi; Tanaka, Kiyoji.

1993-01-01

Radiation-reduced hybrids for mapping of DNA markers in the pericentromeric region of chromosome 10 were developed. A Chinese hamster/human somatic cell hybrid (762-8A) carrying chromosomes 10 and Y as the only human material were exposed to 40,000 rads of irradiation and then rescued by fusion with non-irradiated recipient Chinese hamster cells (GM459). Southern hybridization analyses revealed that 10 of 128 HAT-resistant clones contained human chromosomal fragments corresponding to at least one marker locus between FNRB (10p11.2) and RBP3 (10q11.2). These hybrids were then used to map microdissection clones previously isolated and roughly mapped to this chromosomal region by fluorescence in situ hybridization (FISH). Two of the six microclones studies could be mapped to the proximity of the D10S102 locus. These radiation hybrids are useful for the construction of refined genetic maps of the pericentromeric region of chromosome 10. (author) 50 refs

Development of Structural Covariance From Childhood to Adolescence: A Longitudinal Study in 22q11.2DS

Directory of Open Access Journals (Sweden)

Corrado Sandini

2018-05-01

Full Text Available Background: Schizophrenia is currently considered a neurodevelopmental disorder of connectivity. Still few studies have investigated how brain networks develop in children and adolescents who are at risk for developing psychosis. 22q11.2 Deletion Syndrome (22q11DS offers a unique opportunity to investigate the pathogenesis of schizophrenia from a neurodevelopmental perspective. Structural covariance (SC is a powerful approach to explore morphometric relations between brain regions that can furthermore detect biomarkers of psychosis, both in 22q11DS and in the general population.Methods: Here we implement a state-of-the-art sliding-window approach to characterize maturation of SC network architecture in a large longitudinal cohort of patients with 22q11DS (110 with 221 visits and healthy controls (117 with 211 visits. We furthermore propose a new clustering-based approach to group regions according to trajectories of structural connectivity maturation. We correlate measures of SC with development of working memory, a core executive function that is highly affected in both idiopathic psychosis and 22q11DS. Finally, in 22q11DS we explore correlations between SC dysconnectivity and severity of internalizing psychopathology.Results: In HCs network architecture underwent a quadratic developmental trajectory maturing up to mid-adolescence. Late-childhood maturation was particularly evident for fronto-parietal cortices, while Default-Mode-Network-related regions showed a more protracted linear development. Working memory performance was positively correlated with network segregation and fronto-parietal connectivity. In 22q11DS, we demonstrate aberrant maturation of SC with disturbed architecture selectively emerging during adolescence and correlating more severe internalizing psychopathology. Patients also presented a lack of typical network development during late-childhood, that was particularly prominent for frontal connectivity.Conclusions: Our

Autosomal dominant hereditary spastic paraplegia with axonal sensory motor polyneuropathy maps to chromosome 21q 22.3.

Science.gov (United States)

Peddareddygari, Leema Reddy; Hanna, Philip A; Igo, Robert P; Luo, Yuqun A; Won, Sungho; Hirano, Michio; Grewal, Raji P

2016-01-01

Hereditary spastic paraplegia (HSP) are a genetically and clinically heterogeneous group of disorders. At present, 19 autosomal dominant loci for HSP have been mapped. We ascertained an American family of European descent segregating an autosomal dominant HSP associated with peripheral neuropathy. A genome wide scan was performed with 410 microsatellite repeat marker (Weber lab screening set 16) and following linkage and haplotype analysis, fine mapping was performed. Established genes or loci for HSP were excluded by direct sequencing or haplotype analysis. All established loci for HSP were excluded. Fine mapping suggested a locus on chromosome 21q22.3 flanked by markers D21S1411 and D21S1446 with a maximum logarithm of odds score of 2.05 and was supported by haplotype analysis. A number of candidate genes in this region were analyzed and no disease-producing mutations were detected. We present the clinical and genetic analysis of an American family with autosomal dominant HSP with axonal sensory motor polyneuropathy mapping to a novel locus on chromosome 21q22.3 designated SPG56.

Loss of 11q and 16q in Wilms tumors is associated with anaplasia, tumor recurrence, and poor prognosis.

Science.gov (United States)

Wittmann, Stefanie; Zirn, Birgit; Alkassar, Muhannad; Ambros, Peter; Graf, Norbert; Gessler, Manfred

2007-02-01

Allele loss of chromosome arms 11q and 16q in Wilms tumors has been associated with different clinical parameters in prior studies. To substantiate these findings in a large collection of tumors treated according to the GPOH/SIOP protocol and to narrow down critical regions, we performed loss of heterozygosity (LOH) analyses of chromosome arms 11q and 16q on 225 Wilms tumors. On chromosome arm 11q an overall rate of allele loss of 19.6% (44 of 225 tumors) was found using eleven markers that were almost evenly distributed along the long arm. Chromosome arm 16q was analyzed with six markers selected from gene-rich regions that identified an LOH rate of 18.4% (41/223). Evaluation of LOH with respect to clinical data revealed significant associations of LOH 11q with histology: LOH 11q was 3-4 times more frequent in mixed type and diffuse anaplastic tumors. In contrast, epithelial as well as stromal type tumors never exhibited allele loss on 11q. Furthermore, a significant correlation with tumor recurrence and death was detected, but only for tumors that lost the entire long arm of chromosome 11. Similarly, LOH 16q was correlated with higher risks of later relapse, especially in tumors with complete loss of the long arm. Hence, analyses of LOH on 11q and 16q appear to be helpful to identify tumors with a higher risk of relapse and adverse outcome, which need adjusted therapeutic approaches. Copyright 2006 Wiley-Liss, Inc.

Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study.

Science.gov (United States)

Mekori-Domachevsky, Ehud; Guri, Yael; Yi, James; Weisman, Omri; Calkins, Monica E; Tang, Sunny X; Gross, Raz; McDonald-McGinn, Donna M; Emanuel, Beverly S; Zackai, Elaine H; Zalsman, Gil; Weizman, Abraham; Gur, Ruben C; Gur, Raquel E; Gothelf, Doron

2017-10-01

About one third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop schizophrenia. Notably, a full-blown psychotic disorder is usually preceded by subthreshold symptoms. Therefore, it is important to identify early signs of psychosis in this population, a task that is complicated by the intellectual disabilities typically seen in 22q11.2DS. We aimed to identify subthreshold psychotic symptoms that distinguish 22q11.2DS from other neurodevelopmental disorders. The study included two independent cohorts from Tel Aviv and Philadelphia. 22q11.2DS (N=171) and typically developing (TD; N=832) individuals were enrolled at both sites and further compared to two groups with intellectual disabilities: Williams syndrome (WS; N=21) in the Tel Aviv cohort and idiopathic developmental disabilities (IDD; N=129) in the Philadelphia cohort. Participants and their primary caregivers were interviewed with the Structured Interview for Prodromal Symptoms (SIPS) and psychopathologies were assessed using standardized tools; general cognitive abilities were assessed with the Computerized Neurocognitive Battery. Negative/disorganized subthreshold syndrome was significantly more common in the 22q11.2DS group than in the WS (OR=3.90, 95% CI=1.34-11.34) or IDD (OR=5.05, 95% CI=3.01-10.08) groups. The 22q11.2DS group had higher scores than the two intellectual disabilities groups on several SIPS negative items, including avolition and decreased expression of emotion. Overall, there were few significant correlations between level of cognitive deficits and severity of negative symptoms in 22q11.2DS and only in the Tel Aviv cohort. Our findings suggest that 22q11.2DS individuals at the age of risk for developing psychosis should be closely monitored for negative symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Children with 7q11.23 Duplication Syndrome: Speech, Language, Cognitive, and Behavioral Characteristics and their Implications for Intervention

OpenAIRE

Velleman, Shelley L.; Mervis, Carolyn B.

2011-01-01

7q11.23 duplication syndrome is a recently-documented genetic disorder associated with severe speech delay, language delay, a characteristic facies, hypotonia, developmental delay, and social anxiety. Developmentally appropriate nonverbal pragmatic abilities are demonstrated in socially comfortable situations. Motor speech disorder (Childhood Apraxia of Speech and/or dysarthria), oral apraxia, and/or phonological disorder or symptoms of these disorders are common as are characteristics consis...

Recurrent proximal 18p monosomy and 18q trisomy in a family due to a pericentric inversion.

Science.gov (United States)

Zamani, Ayse Gul; Acar, Aynur; Durakbasi-Dursun, Gul; Yildirim, M Selman; Ceylaner, Serdar; Tuncez, Ebru

2014-05-01

Here, we report on a family with pericentric inversion of chromosome 18 [inv(18)(p11.2q21)] and two recombinants with a duplication of q21 → qter and a deletion of p11.2 → pter regions in a four-generation family. This chromosomal abnormality was inherited in our first patient from the father, while it was transmitted to the second patient from the mother. Array-CGH analysis were used to better characterize duplicated and deleted chromosomal regions and showed no genomic copy number variation (CNV) differences between these two relatives. We discussed genotype-phenotype correlations including previously reported. © 2014 Wiley Periodicals, Inc.

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

Autism, ADHD, Mental Retardation and Behavior Problems in 100 Individuals with 22q11 Deletion Syndrome

Science.gov (United States)

Niklasson, Lena; Rasmussen, Peder; Oskarsdottir, Solveig; Gillberg, Christopher

2009-01-01

This study assessed the prevalence and type of associated neuropsychiatric problems in children and adults with 22q11 deletion syndrome. One-hundred consecutively referred individuals with 22q11 deletion syndrome were given in-depth neuropsychiatric assessments and questionnaires screens. Autism spectrum disorders (ASDs) and/or attention…

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

Association between prematurity and the evolution of psychotic disorders in 22q11.2 deletion syndrome.

Science.gov (United States)

Midbari Kufert, Yael; Nachmani, Ariela; Nativ, Einat; Weizman, Abraham; Gothelf, Doron

2016-12-01

In this study, we report the developmental, physical and psychiatric manifestations of 22q11.2 deletion syndrome (22q11.2DS) in a large Israeli cohort, and search for a possible association between preterm birth and the risk for psychotic disorders. The study population consisted of 128 individuals with 22q11.2DS (77 male, 51 female), aged 1-55 years (mean ± SD 12.9 ± 11.0). All subjects underwent a comprehensive medical evaluation. All subjects older than 5 years (n = 104) were also evaluated psychiatrically. Overall, we found rates of physical manifestations similar to those previously reported in the literature. Psychiatric disorders were very common among our study population, with psychotic disorders occurring in 16.3 % of the psychiatrically evaluated population. We found an association between the presence of psychotic disorders and preterm birth. Our results replicate and extend the findings of a previous work and suggest that the evolution of psychosis in 22q11.2DS is a neurodevelopmental process with early obstetric and medical precursors.

Chromosome duplication in Lolium multiflorum Lam.

Directory of Open Access Journals (Sweden)

Roselaine Cristina Pereira

2014-11-01

Full Text Available Artificial chromosome duplication of diploid genotypes of Lolium multiflorum (2n=2x=14 is worthy to breeding, and aims to increase the expression of traits with agronomic interest. The purpose of this study was to obtain polyploid plants of L. multiflorum from local diploid populations in order to exploit adaptation and future verification of the effects of polyploidy in agronomic traits. Seedlings were immersed in different colchicine solutions for an exposure time of 3h and 24h. Ploidy determination was made by the DNA content and certified by chromosomes counts. The plants confirmed as tetraploids were placed in a greenhouse, and, at flowering, pollen viability was evaluated, and seeds were harvested to assess the stability of the progenies. The percentage of polyploids obtained was 20%. Pollen viability of the tetraploids generated ranged from 58% to 69%. The tetraploid plants obtained in the experiment generated 164 progenies, of which 109 presented DNA content compatible with the tetraploid level, showing stability of chromosome duplication in the filial generation.

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.

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

International Nuclear Information System (INIS)

Grassi, Marcília S.; Jacob, Cristina M. A.; Kulikowski, Leslie D.; Pastorino, Antonio C.; Dutra, Roberta L.; Miura, Nana; Jatene, Marcelo B.; Pegler, Stephanie P.; Kim, Chong A.; Carneiro-Sampaio, Magda

2014-01-01

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

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.

Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families.

Science.gov (United States)

Logue, Mark W; Bauver, Sarah R; Knowles, James A; Gameroff, Marc J; Weissman, Myrna M; Crowe, Raymond R; Fyer, Abby J; Hamilton, Steven P

2012-04-01

Replication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa (IA) and the Columba panic disorder families. We use the fuzzy-clustering method presented by Kaabi et al. [Kaabi et al. (2006); Am J Hum Genet 78: 543-553] to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the IA families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia (CO) data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the IA and CO datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear-associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets. Copyright © 2012 Wiley Periodicals, Inc.

Partial Duplication of Chromosome 8p

African Journals Online (AJOL)

rme

The partial chromosome 8p duplication is a rare syndrome and is ... abnormality of maternal origin that ... second trimester by vaginal bleeding and ... echocardiography, brain CT scan and. MRI. Fig. 1:Conventional karyotype of case 3 showing.

Developmental course of conversational behaviour of children with 22q11.2 deletion syndrome and Williams syndrome

OpenAIRE

Van Den Heuvel, E.; Botting, N.; Boudewijns, I.; Manders, E.; Swillen, A.; Zink, I.

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). We 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 autism spectrum disorders (IID+ASD). Children with 22q11.2DS became less actively involved over time. Lower assertiveness than in children with IID was demonstrated. ...

Hematological malignancies with t(9;11)(p21-22;q23)--a laboratory and clinical study of 125 cases. European 11q23 Workshop participants.

Science.gov (United States)

Swansbury, G J; Slater, R; Bain, B J; Moorman, A V; Secker-Walker, L M

1998-05-01

This paper reports clinical and cytogenetic data from 125 cases with t(9;11)(p21-22;q32) which were accepted for a European Union Concerted Action Workshop on 11q23. This chromosome abnormality is known to occur predominantly in acute myeloid leukemia (AML) FAB type M5a and less often in AML M4; in this series it was also found to occur, uncommonly, in other AML FAB types, in childhood acute lymphoblastic leukemia (ALL) (nine cases), in relatively young patients with myelodysplastic syndrome (MDS) (five cases), acute biphenotypic leukemia (two cases), and acute undifferentiated leukemia (one case). All age groups were represented but 50% of the patients were aged less than 15 years. The t(9;11) was the sole abnormality in 57 cases with AML; trisomy 8 was the most common additional abnormality (23 cases, including seven with further abnormalities), and 28 cases had other additional abnormalities. Among the t(9;11)+ve patients with AML, the white cell count (WBC) and age group were significant predictors of event-free survival; central nervous system (CNS) involvement or karyotype class (sole, with trisomy 8, or with other), also contributed to prognosis although our data could not show these to be independent factors. The best outcome was for patients aged 1-9 years, with low WBC, and with absence of CNS disease or presence of trisomy 8. For patients aged less than 15 years, the event-free survival for ALL patients was not significantly worse than that of AML patients.

22q11 deletion syndrome: Parents' and children's experiences of educational and healthcare provision in the United Kingdom.

Science.gov (United States)

Cohen, Wendy; McCartney, Elspeth; Crampin, Lisa

2017-06-01

22q11 deletion syndrome (22q11DS) is a genetic syndrome, prevalence around 1:4000-1:6000 live births, with a complex array of associated features, impacting on healthcare and educational support. This study reports the perceptions of families and individuals with 22q11DS in relation to these needs. Individuals and families of those with 22q11DS were approached though two national charities - the Max Appeal and 22Crew. An initial observational survey design was used to gather views via questions probing access to healthcare and educational experiences. Thirty-four responses were received and the data subjected to descriptive analysis. Over half of the respondents were diagnosed before the age of 1. Ninety-one percent reported ongoing difficulties with learning at school, compounded by school attendance being compromised as a result of medical interventions. Individuals reported engaging heavily with educational support and a high number of health professions (mean 9.5; mode 10). Age of diagnosis of 22q11DS ranged from birth to nine years. Families had ongoing concerns about aspects of education and healthcare services, and lack of knowledge and awareness of the difficulties faced by individuals with 22q11DS was raised. Healthcare and education providers should be aware of the range of services individuals required on a regular basis so as to provide a more holistic approach to care.

Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

DEFF Research Database (Denmark)

Bisgaard, A-M; Kirchhoff, M; Nielsen, J E

2008-01-01

A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene (ARSA......) and succumbed to metachromatic leukodystrophy (MLD). The other patient had a pseudoallele, which does not lead to MLD. The presenting clinical features and low arylsulfatase A activity were explained, in each patients, by a deletion of 22q13 and, thereby, of one allele of ARSA....

The interaction between neurocognitive functioning, subthreshold psychotic symptoms and pharmacotherapy in 22q11.2 deletion syndrome: A longitudinal comparative study.

Science.gov (United States)

Weinberger, R; Weisman, O; Guri, Y; Harel, T; Weizman, A; Gothelf, D

2018-02-01

The 22q11.2 deletion syndrome (22q11DS) is the most common genetic syndrome associated with schizophrenia. The goal of this study was to evaluate longitudinally the interaction between neurocognitive functioning, the presence of subthreshold psychotic symptoms (SPS) and conversion to psychosis in individuals with 22q11DS. In addition, we attempted to identify the specific neurocognitive domains that predict the longitudinal evolution of positive and negative SPS, as well as the effect of psychiatric medications on 22q11DS psychiatric and cognitive developmental trajectories. Forty-four participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically developing (TD) controls, age range 12-35years, were assessed at two time points (15.2±2.1months apart). Evaluation included the Structured Interview for Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn Computerized Neurocognitive Battery (CNB). 22q11DS individuals with SPS had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in both WS and TD controls. Baseline levels of negative SPS were associated with global neurocognitive performance (GNP), executive function and social cognition deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS individuals treated with psychiatric medications showed significant improvement in GNP score between baseline and follow-up assessments, an improvement that was not seen in untreated 22q11DS. Our results highlight the time-dependent interplay among positive and negative SPS symptoms, neurocognition and pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Fine mapping of genetic polymorphisms of pulmonary tuberculosis within chromosome 18q11.2 in the Chinese population: a case-control study

Directory of Open Access Journals (Sweden)

Dai Yaoyao

2011-10-01

Full Text Available Abstract Background Recently, one genome-wide association study identified a susceptibility locus of rs4331426 on chromosome 18q11.2 for tuberculosis in the African population. To validate the significance of this susceptibility locus in other areas, we conducted a case-control study in the Chinese population. Methods The present study consisted of 578 cases and 756 controls. The SNP rs4331426 and other six tag SNPs in the 100 Kbp up and down stream of rs4331426 on chromosome 18q11.2 were genotyped by using the Taqman-based allelic discrimination system. Results As compared with the findings from the African population, genetic variation of the SNP rs4331426 was rare among the Chinese. No significant differences were observed in genotypes or allele frequencies of the tag SNPs between cases and controls either before or after adjusting for age, sex, education, smoking, and drinking history. However, we observed strong linkage disequilibrium of SNPs. Constructed haplotypes within this block were linked the altered risks of tuberculosis. For example, in comparison with the common haplotype AA(rs8087945-rs12456774, haplotypes AG(rs8087945-rs12456774 and GA(rs8087945-rs12456774 were associated with a decreased risk of tuberculosis, with the adjusted odds ratio(95% confidence interval of 0.34(0.27-0.42 and 0.22(0.16-0.29, respectively. Conclusions Susceptibility locus of rs4331426 discovered in the African population could not be validated in the Chinese population. None of genetic polymorphisms we genotyped were related to tuberculosis in the single-point analysis. However, haplotypes on chromosome 18q11.2 might contribute to an individual's susceptibility. More work is necessary to identify the true causative variants of tuberculosis.

A 11.7-Mb Paracentric Inversion in Chromosome 1q Detected in Prenatal Diagnosis Associated with Familial Intellectual Disability.

Science.gov (United States)

Rigola, Maria A; Baena, Neus; Català, Vicenç; Lozano, Iris; Gabau, Elisabet; Guitart, Miriam; Fuster, Carmen

2015-01-01

Most apparent balanced chromosomal inversions are usually clinically asymptomatic; however, infertility, miscarriages, and mental retardation have been reported in inversion carriers. We present a small family with a paracentric inversion 1q42.13q43 detected in routine prenatal diagnosis. Molecular cytogenetic methods defined the size of the inversion as 11.7 Mb and excluded other unbalanced chromosomal alterations in the patients. Our findings suggest that intellectual disability is caused by dysfunction, disruption, or position effects of genes located at or near the breakpoints involved in this inversion. © 2015 S. Karger AG, Basel.

10p Duplication characterized by fluorescence in situ hybridization

Energy Technology Data Exchange (ETDEWEB)

Wiktor, A.; Feldman, G.L.; Van Dyke, D.L.; Kratkoczki, P.; Ditmars, D.M. Jr. [Henry Ford Hospital, Detroit, MI (United States)

1994-09-01

We describe a patient with severe failure to thrive, mild-moderate developmental delay, cleft lip and palate, and other anomalies. Routine cytogenetic analysis documented a de novo chromosome rearrangement involving chromosome 4, but the origin of the derived material was unknown. Using chromosome specific painting probes, the karyotype was defined as 46,XY,der(4)t(4;10)(q35;p11.23). Characterization of the dup(10p) by fluorescence in situ hybridization (FISH) analysis provides another example of the usefulness of this technology in identifying small deletions, duplications, or supernumerary marker chromosomes. 19 refs., 4 figs.

Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?

Science.gov (United States)

Tomescu, Miralena I; Rihs, Tonia A; Becker, Robert; Britz, Juliane; Custo, Anna; Grouiller, Frédéric; Schneider, Maude; Debbané, Martin; Eliez, Stephan; Michel, Christoph M

2014-08-01

Previous studies have repeatedly found altered temporal characteristics of EEG microstates in schizophrenia. The aim of the present study was to investigate whether adolescents affected by the 22q11.2 deletion syndrome (22q11DS), known to have a 30 fold increased risk to develop schizophrenia, already show deviant EEG microstates. If this is the case, temporal alterations of EEG microstates in 22q11DS individuals could be considered as potential biomarkers for schizophrenia. We used high-density (204 channel) EEG to explore between-group microstate differences in 30 adolescents with 22q11DS and 28 age-matched controls. We found an increased presence of one microstate class (class C) in the 22q11DS adolescents with respect to controls that was associated with positive prodromal symptoms (hallucinations). A previous across-age study showed that the class C microstate was more present during adolescence and a combined EEG-fMRI study associated the class C microstate with the salience resting state network, a network known to be dysfunctional in schizophrenia. Therefore, the increased class C microstates could be indexing the increased risk of 22q11DS individuals to develop schizophrenia if confirmed by our ongoing longitudinal study comparing both the adult 22q11DS individuals with and without schizophrenia, as well as schizophrenic individuals with and without 22q11DS. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Axis I psychiatric diagnoses in adolescents and young adults with 22q11 deletion syndrome

Science.gov (United States)

Ousley, O.Y.; Smearman, E.; Fernandez-Carriba, S.; Rockers, K.A.; Coleman, K.; Walker, E.F.; Cubells, J.F.

2017-01-01

Background 22q11.2 deletion syndrome (22q11DS) associates with schizophrenia spectrum disorders (SSDs), autism spectrum disorders (ASDs), and other psychiatric disorders, but co-occurrence of diagnoses are not well described. Methods We evaluated the co-occurrence of SSDs, ASDs and other axis I psychiatric diagnoses in 31 adolescents and adults with 22q11DS, assessing ASDs using either stringent Collaborative Program for Excellence in Autism (ASD-CPEA) criteria, or less stringent DSM-IV criteria alone (ASD-DSM-IV). Results Ten (32%) individuals met criteria for an SSD, five (16%) for ASD-CPEA, and five others (16%) for ASD-DSM-IV. Of those with ASD-CPEA, one (20%) met SSD criteria. Of those with ASD-DSM-IV, four (80%) met SSD criteria. Depressive disorders (8 individuals; 26%) and anxiety disorders (7; 23%) sometimes co-occurred with SSDs and ASDs. SSDs, ASDs, and anxiety occurred predominantly among males and depression predominantly among females. Conclusions Individuals with 22q11DS can manifest SSDs in the presence or absence of ASDs and other axis I diagnoses. The results suggest that standard clinical care should include childhood screening for ASDs, and later periodic screening for all axis I diagnoses. PMID:23916466

Close linkage of the locus for X chromosome-linked severe combined immunodeficiency to polymorphic DNA markers in Xq11-q13

International Nuclear Information System (INIS)

de Saint Basile, G.; Arveiler, B.; Oberle, I.

1987-01-01

The gene for X chromosome-linked severe combined immunodeficiency (SCID), a disease characterized by a block in early T-cell differentiation, has been mapped to the region Xq11-q13 by linkage analysis with restriction fragment length polymorphisms. High logarithm of odds (lod) scores were obtained with the marker 19.2 (DXS3) and with the marker cpX73 (DXS159) that showed complete cosegregation with the disease locus in the informative families analyzed. Other significant linkages were obtained with several markers from Xq11 to q22. With the help of a recently developed genetic map of the region, it was possible to perform multipoint linkage analysis, and the most likely genetic order is DXS1-(SCID, DXS159)-DXYS1-DXYS12-DXS3, with a maximum multipoint logarithm of odds score of 11.0. The results demonstrate that the SCID locus (gene symbol IMD4) is not closely linked to the locus of Bruton's agammaglobulinemia (a defect in B-cell maturation). They also provide a way for a better estimation of risk for carrier and antenatal diagnosis

Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder.

Science.gov (United States)

Mullegama, Sureni V; Rosenfeld, Jill A; Orellana, Carmen; van Bon, Bregje W M; Halbach, Sara; Repnikova, Elena A; Brick, Lauren; Li, Chumei; Dupuis, Lucie; Rosello, Monica; Aradhya, Swaroop; Stavropoulos, D James; Manickam, Kandamurugu; Mitchell, Elyse; Hodge, Jennelle C; Talkowski, Michael E; Gusella, James F; Keller, Kory; Zonana, Jonathan; Schwartz, Stuart; Pyatt, Robert E; Waggoner, Darrel J; Shaffer, Lisa G; Lin, Angela E; de Vries, Bert B A; Mendoza-Londono, Roberto; Elsea, Sarah H

2014-01-01

Copy number variations associated with abnormal gene dosage have an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID) and autism. We hypothesize that the chromosome 2q23.1 region encompassing MBD5 is a dosage-dependent region, wherein deletion or duplication results in altered gene dosage. We previously established the 2q23.1 microdeletion syndrome and report herein 23 individuals with 2q23.1 duplications, thus establishing a complementary duplication syndrome. The observed phenotype includes ID, language impairments, infantile hypotonia and gross motor delay, behavioral problems, autistic features, dysmorphic facial features (pinnae anomalies, arched eyebrows, prominent nose, small chin, thin upper lip), and minor digital anomalies (fifth finger clinodactyly and large broad first toe). The microduplication size varies among all cases and ranges from 68 kb to 53.7 Mb, encompassing a region that includes MBD5, an important factor in methylation patterning and epigenetic regulation. We previously reported that haploinsufficiency of MBD5 is the primary causal factor in 2q23.1 microdeletion syndrome and that mutations in MBD5 are associated with autism. In this study, we demonstrate that MBD5 is the only gene in common among all duplication cases and that overexpression of MBD5 is likely responsible for the core clinical features present in 2q23.1 microduplication syndrome. Phenotypic analyses suggest that 2q23.1 duplication results in a slightly less severe phenotype than the reciprocal deletion. The features associated with a deletion, mutation or duplication of MBD5 and the gene expression changes observed support MBD5 as a dosage-sensitive gene critical for normal development.

Chromosome break points of T-lymphocytes from atomic bomb survivors

International Nuclear Information System (INIS)

Tanaka, Kimio; Kamada, Nanao; Kuramoto, Atsushi; Ohkita, Takeshi

1980-01-01

Chromosome break points of T-lymphocytes were investigated for 9 atomic bomb survivors estimated to be irradiated with 100 - 630 red. Chromosome aberration was found in 199 cells out of 678 cells investigated, with non-random distribution. The types of the chromosome aberration were, transfer: 56%, deficit: 38%, additional abnormality 3%, and reverse: 2%. High and low incidence of chromosome aberrations were observed at the chromosome numbers of 22, 21, and 13, and 11, 12, and 4, respectively. The aberration numbers per arm were high in 22q, 21q, and 18p and low in 11q, 5p, and 12q. For the distribution of aberration number within a chromosome, 50.7% was observed at the terminal portion and 73% was at the pale band appeared by Q-partial-stain method, suggesting the non-random distribution. The incidence of aberration number in 22q was statistically significant (P 1 chromosome in chronic myelocytic leukemia. The non-random distribution of chromosome break points seemed to reflect the selection effect since irradiation. (Nakanishi, T.)

Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22)(p24;q11)

OpenAIRE

A. N. Chamseddine; P. Etancelin; D. Penther; F. Parmentier; C. Kuadjovi; V. Camus; N. Contentin; P. Lenain; C. Bastard; H. Tilly; F. Jardin

2015-01-01

BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24) that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U) showing a t(9;22)(p24;q11), which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most...

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

Science.gov (United States)

Lecoq, Anne-Lise; Stratakis, Constantine A.; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R.; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; Louiset, Estelle; Lacroix, André; Bouligand, Jérôme; Kamenický, Peter

2017-01-01

GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing’s syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. PMID:28931750

Isodicentric chromosome 21: a novel aberration in acute myeloid leukemia.

Science.gov (United States)

Sankar, M; Tanaka, K; Arif, M; Shintani, T; Kumaravel, T S; Kyo, T; Dohy, H; Kamada, N

1998-11-01

We present here a 78-year-old female patient with acute myeloid leukemia (AML), French-American-British classification M2, exhibiting isodicentric chromosome 21, idic(21)(q22), at the time of diagnosis. The patient had three idic(21)(q22), besides the del(5)(q13q32), add(21)(q22), dic(21;22) (q22;q13), and +22. Fluorescence in situ hybridization studies with whole-chromosome painting and centromere-specific probes for chromosome 21 verified the diagnosis of idic(21)(q22). There were no distinct clinicohematological characteristics of AML with isodicentric 21. The patient was treated with remission-induction therapy followed by consolidation therapy. Two years later, the patient showed the disappearance of isodicentric 21 but retained del(5)(q13q32) and gained other chromosomal abnormalities, +add(17)(p11) and -16. To our knowledge, this is the first report of AML with acquired idic(21)(q22).

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...

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.

USH1K, a novel locus for type I Usher syndrome, maps to chromosome 10p11.21-q21.1.

Science.gov (United States)

Jaworek, Thomas J; Bhatti, Rashid; Latief, Noreen; Khan, Shaheen N; Riazuddin, Saima; Ahmed, Zubair M

2012-10-01

We ascertained two large Pakistani consanguineous families (PKDF231 and PKDF608) segregating profound hearing loss, vestibular dysfunction, and retinitis pigmentosa; the defining features of Usher syndrome type 1 (USH1). To date, seven USH1 loci have been reported. Here, we map a novel locus, USH1K, on chromosome 10p11.21-q21.1. In family PKDF231, we performed a genome-wide linkage screen and found a region of homozygosity shared among the affected individuals at chromosome 10p11.21-q21.1. Meiotic recombination events in family PKDF231 define a critical interval of 11.74 cM (20.20 Mb) bounded by markers D10S1780 (63.83 cM) and D10S546 (75.57 cM). Affected individuals of family PKDF608 were also homozygous for chromosome 10p11.21-q21.1-linked STR markers. Of the 85 genes within the linkage interval, PCDH15, GJD4, FZD4, RET and LRRC18 were sequenced in both families, but no potential pathogenic mutation was identified. The USH1K locus overlaps the non-syndromic deafness locus DFNB33 raising the possibility that the two disorders may be caused by allelic mutations.

22q11.2 deletion syndrome: behaviour problems of children and adolescents and parental stress.

Science.gov (United States)

Briegel, W; Schneider, M; Schwab, K Otfried

2008-11-01

22q11.2 deletion syndrome can be associated with a variety of somatic symptoms, developmental delays and psychiatric disorders. At present, there is little information on behaviour problems, parental stress and possible relations between these factors. Therefore, this study investigates behaviour problems of children and adolescents with 22q11.2DS, and their primary caregivers' stress. Parents of 4-17 year old subjects known to the German 22q11.2 deletion syndrome foundation were anonymously asked to fill out several questionnaires, e.g. the Child Behavior Checklist 4-18 (CBCL/4-18). The primary caregivers of 77/126 children [43 males, 34 females, mean age: 8;0 (4;0-16;11) years] sent back filled-out questionnaires. Forty-six of 76 subjects were rated as clinical on at least one of the CBCL-scales. Males had significantly higher scores on the total problems scale and the internalizing problems scale than females. The patients' age correlated with several CBCL-scales. Eleven of 49 subjects were suspicious of an autism spectrum disorder. Compared with the general population, but not with other parents of mentally and/or physically handicapped children, the primary caregivers experienced higher levels of stress, but showed normal life satisfaction. In spite of high rates of clinical behaviour problems among children and adolescents with 22q11.2DS and despite increased parental stress, most primary caregivers seem to have effective coping strategies, e.g. partnership support, to sustain normal levels of life satisfaction.

Detection of Chromosome X;18 Breakpoints and Translocation of the Xq22.3;18q23 Regions Resulting in Variable Fertility Phenotypes

Directory of Open Access Journals (Sweden)

Attila Szvetko

2012-01-01

Full Text Available We describe a familial pattern of gonosomal-autosomal translocation between the X and 18 chromosomes, balanced and unbalanced forms, in male and female siblings. The proposita was consulted for hypergonadotropic hypogonadism. Karyotype analysis revealed a balanced 46, X, t(X;18(q22.3;q23 genotype. The sister of the proband presented with oligomenorrhea with irregular menses and possesses an unbalanced form of the translocation 46, X, der(X, t(X;18(q22.3;q23. The brother of the proband was investigated and was found to possess the balanced form of the same translocation, resulting in disrupted spermatogenesis. Maternal investigation revealed the progenitor karyotype 46, X, t(X;18(q22.3;q23. Maternal inheritance and various genomic events contributed to the resultant genotypes. Primary infertility was initially diagnosed in all progeny; however, the male individual recently fathered twins. We briefly review the mechanisms associated with X;18 translocations and describe a pattern of inheritance, where breakpoints and translocation of the Xq22.3;18q23 regions have resulted in variable fertility.

Multimodal MRI reveals structural connectivity differences in 22q11 deletion syndrome related to impaired spatial working memory

NARCIS (Netherlands)

O'Hanlon, Erik; Howley, Sarah; Prasad, Sarah; McGrath, Jane; Leemans, Alexander; McDonald, Colm; Garavan, Hugh; Murphy, Kieran C

2016-01-01

INTRODUCTION: Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional

Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay.

Science.gov (United States)

Nakamine, Alisa; Ouchanov, Leonid; Jiménez, Patricia; Manghi, Elina R; Esquivel, Marcela; Monge, Silvia; Fallas, Marietha; Burton, Barbara K; Szomju, Barbara; Elsea, Sarah H; Marshall, Christian R; Scherer, Stephen W; McInnes, L Alison

2008-03-01

Duplications of 17(p11.2p11.2) have been associated with various behavioral manifestations including attention deficits, obsessive-compulsive symptoms, autistic traits, and language delay. We are conducting a genetic study of autism and are screening all cases for submicroscopic chromosomal abnormalities, in addition to standard karyotyping, and fragile X testing. Using array-based comparative genomic hybridization analysis of data from the Affymetrix GeneChip(R) Human Mapping Array set, we detected a duplication of approximately 3.3 Mb on chromosome 17p11.2 in a male child with autism and severe expressive language delay. The duplication was confirmed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction. Gene expression analyses revealed increased expression of three candidate genes for the Smith-Magenis neurobehavioral phenotype, RAI1, DRG2, and RASD1, in transformed lymphocytes from Case 81A, suggesting gene dosage effects. Our results add to a growing body of evidence suggesting that duplications of 17(p11.2p11.2) result in language delay as well as autism and related phenotypes. As Smith-Magenis syndrome is also associated with language delay, a gene involved in acquisition of language may lie within this interval. Whether a parent of origin effect, gender of the case, the presence of allelic variation, or changes in expression of genes outside the breakpoints influence the resultant phenotype remains to be determined. (c) 2007 Wiley-Liss, Inc.

Evaluación citogenética y de pérdida de la heterocigosidad de la región 22q11.2 en pacientes con el Síndrome de DiGeorge = Cytogenetic evaluation and loss of heterozigocity of chromosome 22q11.2 in patients with the DiGeorge syndrome

Directory of Open Access Journals (Sweden)

Gallego García, Germán Andreo

2011-09-01

Full Text Available Objetivo: evaluar la utilidad de la PCR para marcadores microsatélites (PCR-STR en la región 22q11.2 en el ADN genómico, para identificar microdeleciones en pacientes con síndrome de DiGeorge (SDG. Materiales y Métodos: se hizo un análisis de las historias clínicas de tres niñas con SDG y se investigaron deleciones en el cromosoma 22q11.2 mediante FISH y PCR-STR. Resultados: la FISH logró detectar deleciones en 22q11.2 en dos de las tres pacientes. Por su parte, por medio de la PCR-STR, se logró establecer que la paciente n.º 1 presentaba una deleción de 1,5 Mb proximal al centrómero, la segunda de mayor frecuencia en los pacientes con SDG. La deleción fue de origen paterno. Para caracterizar el defecto molecular en las otras pacientes, sería necesario acoplar estudios de cromatografía a este método, que permitan determinar el tamaño molecular de cada uno de los alelos parentales, o bien, ampliar este análisis con más microsatélites informativos ubicados en la región 22q11.2 para así definir más precisamente el tamaño de la deleción. Conclusiones: la PCR-STR en el ADN genómico es una alternativa para identificar deleciones que afectan microsatélites en la región 22q11.2 a un menor costo que la FISH y con resultados más rápidos; al mismo tiempo permite definir el origen parental y el tamaño de la microdeleción. Esta información es valiosa para identificar los genes asociados con las características clínicas del síndrome.

Chromosomal organization of adrenergic receptor genes

International Nuclear Information System (INIS)

Yang-Feng, T.L.; Xue, Feiyu; Zhong, Wuwei; Cotecchia, S.; Frielle, T.; Caron, M.G.; Lefkowitz, R.J.; Francke, U.

1990-01-01

The adrenergic receptors (ARs) (subtypes α 1 , α 2 , β 1 , and β 2 ) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. The authors have previously assigned the genes for β 2 -and α 2 -AR to human chromosomes 5 and 10, respectively. By Southern analysis of somatic cell hybrids and in situ chromosomal hybridization, they have now mapped the α 1 -AR gene to chromosome 5q32→q34, the same position as β 2 -AR, and the β 1 -AR gene to chromosome 10q24→q26, the region where α 2 -AR, is located. In mouse, both α 2 -and β 1 -AR genes were assigned to chromosome 19, and the α 1 -AR locus was localized to chromosome 11. Pulsed field gel electrophoresis has shown that the α 1 -and β 2 -AR genes in humans are within 300 kilobases (kb) and the distance between the α 2 - and β 1 -AR genes is <225 kb. The proximity of these two pairs of AR genes and the sequence similarity that exists among all the ARs strongly suggest that they are evolutionarily related. Moreover, they likely arose from a common ancestral receptor gene and subsequently diverged through gene duplication and chromosomal duplication to perform their distinctive roles in mediation the physiological effects of catecholamines. The AR genes thus provide a paradigm for understanding the evolution of such structurally conserved yet functionally divergent families off receptor molecules

Extracorporeal membrane oxygenation in children with heart disease and del22q11 syndrome: a review of the Extracorporeal Life Support Organization Registry.

Science.gov (United States)

Prodhan, P; Gossett, J M; Rycus, P T; Gupta, P

2015-11-01

The study objective was to evaluate outcomes among children with del22q11 (DiGeorge) syndrome supported on ECMO for heart disease. The ELSO registry database was queried to include all children syndrome and with no del22q11 syndrome. Eighty-eight ECMO runs occurred in children with del22q11 syndrome while 2694 ECMO runs occurred in children without del22q11 syndrome. For patients with heart defects receiving ECMO, del22q11 syndrome did not confer a significant mortality risk or an increased risk of infectious complications before or while on ECMO support. Neither the duration of ECMO nor mechanical ventilation prior to ECMO deployment were prolonged in patients with del22q11 syndrome compared to the controls. © The Author(s) 2015.

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…

Evaluation of 6 candidate genes on chromosome 11q23 for coeliac disease susceptibility: a case control study

Directory of Open Access Journals (Sweden)

Close Eimear

2010-05-01

Full Text Available Abstract Background Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance. The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. Methods We have evaluated six candidate genes in one of these regions (11q23, namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. Results Promotor SNPs (-607, -137 in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P IL18-137/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C/-137C (P Conclusion Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine's role in maintaining inflammation in active CD.

Complex distal 10q rearrangement in a girl with mild intellectual disability: follow up of the patient and review of the literature of non-acrocentric satellited chromosomes.

Science.gov (United States)

Sarri, Catherine; Douzgou, Sofia; Gyftodimou, Yolanda; Tümer, Zeynep; Ravn, Kirstine; Pasparaki, Angela; Sarafidou, Theologia; Kontos, Harry; Kokotas, Haris; Karadima, Georgia; Grigoriadou, Maria; Pandelia, Effie; Theodorou, Virginia; Moschonas, Nicholas K; Petersen, Michael B

2011-11-01

We report on an intellectually disabled girl with a de novo satellited chromosome 10 (10qs) and performed a review of the literature of the non-acrocentric satellited chromosomes (NASC). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited non-acrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is, to our knowledge, the third report of a 10qs chromosome. The phenotype observed in the proband prompted a search for a structural rearrangement of chromosome 10q. By microsatellite analysis we observed a 4 Mb deletion on the long arm of chromosome 10, approximately 145 kb from the telomere. FISH and array CGH analyses revealed a complex rearrangement involving in range from the centromere to the telomere: A 9.64 Mb 10q26.11-q26.2 duplication, a 1.3 Mb region with no copy number change, followed by a 5.62 Mb 10q26.2-q26.3 deletion and a translocation of satellite material. The homology between the repeat sequences at 10q subtelomere region and the sequences on the acrocentric short arms may explain the origin of the rearrangement and it is likely that the submicroscopic microdeletion and microduplication are responsible for the abnormal phenotype in our patient. The patient presented here, with a 15-year follow-up, manifests a distinct phenotype different from the 10q26 pure distal monosomy and trisomy syndromes. Copyright © 2011 Wiley Periodicals, Inc.

USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23.

Science.gov (United States)

Ahmed, Z M; Riazuddin, S; Khan, S N; Friedman, P L; Riazuddin, S; Friedman, T B

2009-01-01

Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, progressive loss of vision attributable to retinitis pigmentosa (RP) and variable vestibular function. Three clinical types have been described with type I (USH1) being the most severe. To date, six USH1 loci have been reported. We ascertained two large Pakistani consanguineous families segregating profound hearing loss, vestibular dysfunction, and RP, the defining features of USH1. In these families, we excluded linkage of USH to the 11 known USH loci and subsequently performed a genome-wide linkage screen. We found a novel USH1 locus designated USH1H that mapped to chromosome 15q22-23 in a 4.92-cM interval. This locus overlaps the non-syndromic deafness locus DFNB48 raising the possibility that the two disorders may be caused by allelic mutations.

Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis.

Science.gov (United States)

Padula, Maria Carmela; Schaer, Marie; Armando, Marco; Sandini, Corrado; Zöller, Daniela; Scariati, Elisa; Schneider, Maude; Eliez, Stephan

2018-01-17

Patients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile. In this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach. Our results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS. These results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.

The role of COMT and plasma proline in the variable penetrance of autistic spectrum symptoms in 22q11.2 deletion syndrome

NARCIS (Netherlands)

Hidding, E.; Swaab, H.; de Sonneville, L. M J; van Engeland, H.; Vorstman, J. A S

2016-01-01

This paper examines how COMT158 genotypes and plasma proline levels are associated with variable penetrance of social behavioural and social cognitive problems in 22q11.2 deletion syndrome (22q11DS). Severity of autistic spectrum symptoms of 45 participants with 22q11DS was assessed using the Autism

A genome-wide scan for autoimmune thyroiditis in the Old Order Amish: replication of genetic linkage on chromosome 5q11.2-q14.3.

Science.gov (United States)

Allen, Elsie M; Hsueh, Wen-Chi; Sabra, Mona M; Pollin, Toni I; Ladenson, Paul W; Silver, Kristi D; Mitchell, Braxton D; Shuldiner, Alan R

2003-03-01

Autoimmune thyroiditis (AITD) is a common disorder characterized by circulating antibodies to epitopes of thyroid tissue and hypothyroidism (Hashimoto's thyroiditis or AITD-hypothyroidism), although many subjects with AITD are euthyroid. Current evidence suggests that AITD is familial and polygenic. We studied AITD in a homogeneous founder Caucasian population, the Old Order Amish of Lancaster County, Pennsylvania. We found autoimmune thyroiditis, defined by the presence of circulating antimicrosomal antibodies, to be relatively common in the Amish, with a prevalence of 22.7%. The prevalence of AITD-hypothyroidism was 9.2%. We performed a genome-wide linkage analysis with 373 short tandem repeat markers in 445 subjects from 29 families. We observed suggestive evidence of linkage of AITD to a locus on chromosome 5q11.2-q14.3 (LOD, 2.30; P = 0.0006 at 94 cM; closest marker, D5S428), a region that was previously reported to be linked to AITD-hypothyroidism in a Japanese study. AITD-hypothyroidism showed a more modest linkage peak to the same region (LOD, 1.46; P = 0.005). Possible linkage (nominal P Amish.

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…

A case report of two male siblings with autism and duplication of Xq13-q21, a region including three genes predisposing for autism.

Science.gov (United States)

Wentz, Elisabet; Vujic, Mihailo; Kärrstedt, Ewa-Lotta; Erlandsson, Anna; Gillberg, Christopher

2014-05-01

Autism spectrum disorder, severe behaviour problems and duplication of the Xq12 to Xq13 region have recently been described in three male relatives. To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1-q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication.

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…

Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23.

Science.gov (United States)

Mowat, D R; Croaker, G D; Cass, D T; Kerr, B A; Chaitow, J; Adès, L C; Chia, N L; Wilson, M J

1998-01-01

We have identified six children with a distinctive facial phenotype in association with mental retardation (MR), microcephaly, and short stature, four of whom presented with Hirschsprung (HSCR) disease in the neonatal period. HSCR was diagnosed in a further child at the age of 3 years after investigation for severe chronic constipation and another child, identified as sharing the same facial phenotype, had chronic constipation, but did not have HSCR. One of our patients has an interstitial deletion of chromosome 2, del(2)(q21q23). These children strongly resemble the patient reported by Lurie et al with HSCR and dysmorphic features associated with del(2)(q22q23). All patients have been isolated cases, suggesting a contiguous gene syndrome or a dominant single gene disorder involving a locus for HSCR located at 2q22-q23. Review of published reports suggests that there is significant phenotypic and genetic heterogeneity within the group of patients with HSCR, MR, and microcephaly. In particular, our patients appear to have a separate disorder from Goldberg-Shprintzen syndrome, for which autosomal recessive inheritance has been proposed because of sib recurrence and consanguinity in some families. Images PMID:9719364

Recombinant chromosome 7 in a mosaic 45,X/47,XXX patient.

Science.gov (United States)

Tirado, Carlos A; Gotway, Garrett; Torgbe, Emmanuel; Iyer, Santha; Dallaire, Stephanie; Appleberry, Taylor; Suterwala, Mohamed; Garcia, Rolando; Valdez, Federico; Patel, Sangeeta; Koduru, Prasad

2012-01-01

Individuals with pericentric inversions are at risk for producing offspring with chromosomal gains and losses, while those carrying paracentric inversions usually produce unviable gametes [Madan, 1995]. In this current study, we present a newborn with dysmorphic features and malformations, whose karyotype showed an abnormal copy of chromomosome 7 described at first as add(7)(q32) as well as mos 45,X/47,XXX. Array comparative genomic hybridization (CGH) revealed an interstitial deletion in the long arm of chromosome 7 involving bands q35 to q36.3 but retaining the 7q subtelomere. The patient's deletion is believed to be due to meiotic recombination in the inversion loop in the phenotypically normal father who seems to carry two paracentric inversions in the long arm of chromosome 7, which was described as rec(7)(7pter- > q35::q36.3- > 7qter)pat. The abnormal copy of chromosome 7 in the father has been described as: der(7)(7pter- > q22.1::q36.3- > q35::q22.1- > q35::q36.3- > 7qter). This is a unique karyotype that to our knowledge has not been previously reported in the literature and predisposes to meiotic recombination that can result in deletions or duplications of 7q35-36. Copyright © 2011 Wiley Periodicals, Inc.

The idic(X)(q13) in myeloid malignancies: breakpoint clustering in segmental duplications and association with TET2 mutations

DEFF Research Database (Denmark)

Paulsson, Kajsa; Haferlach, Claudia; Fonatsch, Christa

2010-01-01

Myelodysplastic syndromes and acute myeloid leukemia with an isodicentric X chromosome [idic(X)(q13)] occur in elderly women and frequently display ringed sideroblasts. Because of the rarity of idic(X)(q13), little is known about its formation, whether a fusion gene is generated, and patterns...... of additional aberrations. We here present an SNP array study of 14 idic(X)-positive myeloid malignancies, collected through an international collaborative effort. The breakpoints clustered in two regions of segmental duplications and were not in a gene, making dosage effects from the concurrent gain of Xpter......-q13 and loss of Xq13-qter, rather than a fusion gene, the most likely pathogenetic outcome. Methylation analysis revealed involvement of the inactive X chromosomes in five cases and of the active in two. The ABCB7 gene, mutated in X-linked sideroblastic anemia and spinocerebellar ataxia...

Sorting by Cuts, Joins, and Whole Chromosome Duplications.

Science.gov (United States)

Zeira, Ron; Shamir, Ron

2017-02-01

Genome rearrangement problems have been extensively studied due to their importance in biology. Most studied models assumed a single copy per gene. However, in reality, duplicated genes are common, most notably in cancer. In this study, we make a step toward handling duplicated genes by considering a model that allows the atomic operations of cut, join, and whole chromosome duplication. Given two linear genomes, [Formula: see text] with one copy per gene and [Formula: see text] with two copies per gene, we give a linear time algorithm for computing a shortest sequence of operations transforming [Formula: see text] into [Formula: see text] such that all intermediate genomes are linear. We also show that computing an optimal sequence with fewest duplications is NP-hard.

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.

Oral health and 22q11 deletion syndrome: thoughts and experiences from the parents' perspectives.

Science.gov (United States)

Klingberg, Gunilla; Hallberg, Ulrika; Oskarsdóttir, Sólveig

2010-07-01

22q11 deletion syndrome (22q11DS) is one of the most common multiple anomaly syndromes, and many dentists are likely to meet patients with the syndrome. Odontological research has focused on describing and analysing conditions/concepts based on the current state of knowledge within the dental profession. Yet, these research topics are not necessarily the most important issues for the patients. To explore and describe, by use of Grounded theory, parents' experiences of oral health issues and needs for dental care in their children with 22q11DS. Twelve parents from different regions in Sweden were interviewed. Analyses were carried out according to Grounded theory. Parents recognised good oral health as important for the wellbeing of their children. Oral health was a concern and the parents described the fight for this as struggling in vain for good oral health in their child. Parents not only described their children's oral health as important but also hard to gain. Thus, it is important that all patients with disabilities, regardless of whether there is a defined medical diagnosis or not, are identified and well taken care of in the dental care system.