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Sample records for clinical genetics conference

  1. Disability rights in dialogue with clinical genetics conference, May 31 to June 2, 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The issue of prenatal diagnosis and selective abortion has been hotly debated in the medical, genetic counselling, feminist, parents, disability rights and bio-ethics literature, each of the various positions critiquing each other. People from the disability rights community in particular have began to articulate a critical view of the practice of widespread prenatal diagnosis with intent to abort because the pregnancy might result in a child with a disability. Unfortunately, people from the various disciplines and perspectives, such as bioethics, disability rights, feminism and so forth, by and large, have tended only to write for themselves and their colleagues. Few people have crossed disciplines to try to talk to people with other views. The rapid advances of genome research have continued to produce new prenatal tests, raising many complex ethical questions regarding the applications of prenatal testing. But the widely disparate positions of the various factions has made it difficult to move toward formulation of public policy change necessary to encompass these new genetic technologies. Genetic counselling is in the front lines of the controversial social and ethical issues arising from prenatal diagnosis, in its interface between medical science and the consumer of services. The primary intent of the conference was to invite and facilitate productive dialogue between individuals and groups of people who have traditionally not interacted as a result of their disparate views on these issues and to learn from this process, emphasizing the involvement of people with disabilities and people who work in clinical genetics.

  2. AACR Special Conference: Advances in Breast Cancer Research – Genetics, Biology, and Clinical Implications, Huntington Beach, California, USA, 8–12 October 2003

    OpenAIRE

    Welm, Alana L.

    2003-01-01

    The recent meeting 'Advances in Breast Cancer Research – Genetics, Biology, and Clinical Implications' was an American Association for Cancer Research (AACR) Special Conference in Cancer Research, for which the underwriting sponsor was the Avon Foundation. Presentations were made from prominent scientists on several relevant basic science and clinic-oriented topics, including mammary stem cells and development, steroid receptors, matrix and stromal–epithelial interactions, oncogene signaling ...

  3. The 50th Annual Maize Genetics Conference

    Energy Technology Data Exchange (ETDEWEB)

    Cone, Karen

    2014-03-26

    The 50th Annual Maize Genetics Conference was held February 27 - March 2, 2008 at the Marriott Wardman Park Hotel in Washington, D.C. As the golden anniversary of the Conference and coinciding with the release of a draft of the maize genome sequence, this was a special meeting. To publicize this unique occasion, meeting organizers hosted a press conference, which was attended by members of the press representing science and non-science publications, and an evening reception at the Smithsonian National Museum of Natural History, where the draft sequence was announced and awards were presented to Dr. Mary Clutter and Senator Kit Bond to thank them for their outstanding contributions to maize genetics and genomics research. As usual, the Conference provided an invigorating forum for exchange of recent research results in many areas of maize genetics, e.g., cytogenetics, development, molecular genetics, transposable element biology, biochemical genetics, and genomics. Results were shared via both oral and poster presentations. Invited talks were given by four distinguished geneticists: Vicki Chandler, University of Arizona; John Doebley, University of Wisconsin; Susan Wessler, University of Georgia; and Richard Wilson, Washington University. There were 46 short talks and 241 poster presentations. The Conference was attended by over 500 participants. This included a large number of first-time participants in the meeting and an increasingly visible presence by individuals from underrepresented groups. Although we do not have concrete counts, there seem to be more African American, African and Hispanic/Latino attendees coming to the meeting than in years past. In addition, this meeting attracted many participants from outside the U.S. Student participation continues to be hallmark of the spirit of free exchange and cooperation characteristic of the maize genetics community. With the generous support provided by DOE, USDA NSF, and corporate/private donors, organizers were

  4. Genetics of multifactorial disorders: proceedings of the 6th Pan Arab Human Genetics Conference.

    Science.gov (United States)

    Nair, Pratibha; Bizzari, Sami; Rajah, Nirmal; Assaf, Nada; Al-Ali, Mahmoud Taleb; Hamzeh, Abdul Rezzak

    2016-01-01

    The 6th Pan Arab Human Genetics Conference (PAHGC), "Genetics of Multifactorial Disorders" was organized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in Dubai, United Arab Emirates from 21 to 23 January, 2016. The PAHGCs are held biennially to provide a common platform to bring together regional and international geneticists to share their knowledge and to discuss common issues. Over 800 delegates attended the first 2 days of the conference and these came from various medical and scientific backgrounds. They consisted of geneticists, molecular biologists, medical practitioners, postdoctoral researchers, technical staff (e.g., nurses and lab technicians) and medical students from 35 countries around the world. On the 3rd day, a one-day workshop on "Genetic Counseling" was delivered to 26 participants. The conference focused on four major topics, namely, diabetes, genetics of neurodevelopmental disorders, congenital anomalies and cancer genetics. Personalized medicine was a recurrent theme in most of the research presented at the conference, as was the application of novel molecular findings in clinical settings. This report discusses a summary of the presentations from the meeting. PMID:27095177

  5. Feline genetics: clinical applications and genetic testing.

    Science.gov (United States)

    Lyons, Leslie A

    2010-11-01

    DNA testing for domestic cat diseases and appearance traits is a rapidly growing asset for veterinary medicine. Approximately 33 genes contain 50 mutations that cause feline health problems or alterations in the cat's appearance. A variety of commercial laboratories can now perform cat genetic diagnostics, allowing both the veterinary clinician and the private owner to obtain DNA test results. DNA is easily obtained from a cat via a buccal swab with a standard cotton bud or cytological brush, allowing DNA samples to be easily sent to any laboratory in the world. The DNA test results identify carriers of the traits, predict the incidence of traits from breeding programs, and influence medical prognoses and treatments. An overall goal of identifying these genetic mutations is the correction of the defect via gene therapies and designer drug therapies. Thus, genetic testing is an effective preventative medicine and a potential ultimate cure. However, genetic diagnostic tests may still be novel for many veterinary practitioners and their application in the clinical setting needs to have the same scrutiny as any other diagnostic procedure. This article will review the genetic tests for the domestic cat, potential sources of error for genetic testing, and the pros and cons of DNA results in veterinary medicine. Highlighted are genetic tests specific to the individual cat, which are a part of the cat's internal genome. PMID:21147473

  6. Clinical Genetic Testing in Epilepsy

    OpenAIRE

    Mefford, Heather C.

    2015-01-01

    New technologies for mutation detection in the human genome have greatly increased our understanding of epilepsy genetics. Application of genomic technologies in the clinical setting allows for more efficient genetic diagnosis in some patients; therefore, it is important to understand the types of tests available and the types of mutations that can be detected. Making a genetic diagnosis improves overall patient care by enhancing prognosis and recurrence risk counseling and informing treatmen...

  7. Ethical dilemmas in clinical genetics.

    OpenAIRE

    Young, I D

    1984-01-01

    This paper discusses the results of a survey of medical and paramedical opinion relating to various difficult ethical issues in clinical genetics. These include the confidentiality of the doctor-patient relationship, prenatal diagnosis and termination, and Huntington's chorea. It is suggested that this method provides a useful means of assessing what is ethically acceptable in contemporary society.

  8. The use of online discussions for post-clinical conference.

    Science.gov (United States)

    Berkstresser, Kristie

    2016-01-01

    Nurse educators, at every level of pre-licensure nursing education, are charged with developing critical thinking skills within their students. Post-clinical conference is one teaching strategy that nurse educators can employ to help promote the development of critical thinking skills in pre-licensure nursing students. However, traditional face-to-face post-clinical conference is marred with issues and concerns, as identified in the nursing education literature. An alternative to face-to-face post-clinical conference, asynchronous online learning environment, mitigates the issues and concerns associated with traditional post-clinical conference. Adult learning theory supports the use of asynchronous online learning environment because the asynchronous online learning environment promotes student-centered teaching strategy in place of teacher-centered learning, which by its nature traditional face-to-face post-clinical conference tends to support. PMID:26159285

  9. The Application of Clinical Genetics

    Directory of Open Access Journals (Sweden)

    Maurer MH

    2012-02-01

    Full Text Available Martin H MaurerDepartment of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany; Mariaberg Hospital for Child and Adolescent Psychiatry, Gammertingen, GermanyIn 2012, The Application of Clinical Genetics enters its fifth year of publication. The journal has had a change of Editor-in-Chief: Dr David H Tegay stepped down and I was appointed to serve as the new Editor-in-Chief. As his successor, I thank Dr Tegay for his great work for the journal. I hope I can continue his successful editorial contributions. Moreover, I thank the many reviewers for their sustained support of the journal.The Application of Clinical Genetics is dedicated to open access publishing – as all Dove Press journals are. This means that authors will be charged for the publication process, but the acceptance of a manuscript is based solely on its scientific quality. This is what I will be responsible for as Editor-in-Chief. The team at Dove Press is a constant help with all administrative duties concerning peer reviewal, and I want to express my thanks for their prompt and reliable help. The field of clinical genetics is facing new challenges with the broad availability of large-scale screening methods for gene mutations, such as high-throughput sequencing and biochips. This means that ethical issues regarding the handling of genetic information must be addressed, both for the individual and for society.1–3 For example, sequencing of cell-free, fetal nucleic acids in the maternal blood to locate fetal aneuploidy, especially trisomy 21, may become broadly available soon, with even faster results than conventional methods such as amniocentesis.

  10. Genetics of multifactorial disorders: proceedings of the 6th Pan Arab Human Genetics Conference

    OpenAIRE

    Nair, Pratibha; Bizzari, Sami; Rajah, Nirmal; Assaf, Nada; Al-Ali, Mahmoud Taleb; Hamzeh, Abdul Rezzak

    2016-01-01

    The 6th Pan Arab Human Genetics Conference (PAHGC), “Genetics of Multifactorial Disorders” was organized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in Dubai, United Arab Emirates from 21 to 23 January, 2016. The PAHGCs are held biennially to provide a common platform to bring together regional and international geneticists to share their knowledge and to discuss common issues. Over 800 delegates attended the first 2 days of the conference and these came from various medic...

  11. 7th International Conference on Genetic and Evolutionary Computing

    CERN Document Server

    Krömer, Pavel; Snášel, Václav

    2014-01-01

    Genetic and Evolutionary Computing This volume of Advances in Intelligent Systems and Computing contains accepted papers presented at ICGEC 2013, the 7th International Conference on Genetic and Evolutionary Computing. The conference this year was technically co-sponsored by The Waseda University in Japan, Kaohsiung University of Applied Science in Taiwan, and VSB-Technical University of Ostrava. ICGEC 2013 was held in Prague, Czech Republic. Prague is one of the most beautiful cities in the world whose magical atmosphere has been shaped over ten centuries. Places of the greatest tourist interest are on the Royal Route running from the Powder Tower through Celetna Street to Old Town Square, then across Charles Bridge through the Lesser Town up to the Hradcany Castle. One should not miss the Jewish Town, and the National Gallery with its fine collection of Czech Gothic art, collection of old European art, and a beautiful collection of French art. The conference was intended as an international forum for the res...

  12. 8th International Conference on Genetic and Evolutionary Computing

    CERN Document Server

    Yang, Chin-Yu; Lin, Chun-Wei; Pan, Jeng-Shyang; Snasel, Vaclav; Abraham, Ajith

    2015-01-01

    This volume of Advances in Intelligent Systems and Computing contains accepted papers presented at ICGEC 2014, the 8th International Conference on Genetic and Evolutionary Computing. The conference this year was technically co-sponsored by Nanchang Institute of Technology in China, Kaohsiung University of Applied Science in Taiwan, and VSB-Technical University of Ostrava. ICGEC 2014 is held from 18-20 October 2014 in Nanchang, China. Nanchang is one of is the capital of Jiangxi Province in southeastern China, located in the north-central portion of the province. As it is bounded on the west by the Jiuling Mountains, and on the east by Poyang Lake, it is famous for its scenery, rich history and cultural sites. Because of its central location relative to the Yangtze and Pearl River Delta regions, it is a major railroad hub in Southern China. The conference is intended as an international forum for the researchers and professionals in all areas of genetic and evolutionary computing.

  13. 9th International Conference on Genetic and Evolutionary Computing

    CERN Document Server

    Lin, Jerry; Pan, Jeng-Shyang; Tin, Pyke; Yokota, Mitsuhiro; Genetic and Evolutionary Computing

    2016-01-01

    This volume of Advances in Intelligent Systems and Computing contains accepted papers presented at ICGEC 2015, the 9th International Conference on Genetic and Evolutionary Computing. The conference this year was technically co-sponsored by Ministry of Science and Technology, Myanmar, University of Computer Studies, Yangon, University of Miyazaki in Japan, Kaohsiung University of Applied Science in Taiwan, Fujian University of Technology in China and VSB-Technical University of Ostrava. ICGEC 2015 is held from 26-28, August, 2015 in Yangon, Myanmar. Yangon, the most multiethnic and cosmopolitan city in Myanmar, is the main gateway to the country. Despite being the commercial capital of Myanmar, Yangon is a city engulfed by its rich history and culture, an integration of ancient traditions and spiritual heritage. The stunning SHWEDAGON Pagoda is the center piece of Yangon city, which itself is famous for the best British colonial era architecture. Of particular interest in many shops of Bogyoke Aung San Market,...

  14. Additional mechanisms conferring genetic susceptibility to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Miguel Calero

    2015-04-01

    Full Text Available Familial Alzheimer's disease (AD, mostly associated with early onset, is caused by mutations in three genes (APP, PSEN1 and PSEN2 involved in the production of the amyloid  peptide. In contrast, the molecular mechanisms that trigger the most common late onset sporadic AD remain largely unknown. With the implementation of an increasing number of case-control studies and the upcoming of large-scale genome-wide association studies (GWAS there is a mounting list of genetic risk factors associated to common genetic variants that have been associated to sporadic AD. Besides APOE, that presents a strong association with the disease (OR~4, the rest of these genes have moderate or low degrees of association, with OR ranging from 0.88 to 1.23. Taking together, these genes may account only for a fraction of the attributable AD risk and therefore, rare variants and epistastic gene interactions should be taken into account in order to get the full picture of the genetic risks associated to AD. Here, we review recent whole-exome studies looking for rare variants, somatic brain mutations with a strong association to the disease, and several studies dealing with epistasis as additional mechanisms conferring genetic susceptibility to AD. Altogether, recent evidence underlines the importance of defining molecular and genetic pathways and networks rather than the contribution of specific genes.

  15. Tuberous sclerosis - clinical manifestations and genetic implications

    International Nuclear Information System (INIS)

    Twenty-five patients with tuberous sclerosis have been studied with regard to their clinical manifestations, radiological features and genetic background. The practical implications of the condition in southern Africa are reviewed with reference to the literature

  16. Twenty-second Fungal Genetics Conference - Asilomar, 2003

    Energy Technology Data Exchange (ETDEWEB)

    Jonathan D. Walton

    2003-06-30

    The purpose of the Twenty Second Fungal Genetics Conference is to bring together scientists and students who are interested in genetic approaches to studying the biology of filamentous fungi. It is intended to stimulate thinking and discussion in an atmosphere that supports interactions between scientists at different levels and in different disciplines. Topics range from the basic to the applied. Filamentous fungi impact human affairs in many ways. In the environment they are the most important agents of decay and nutrient turnover. They are used extensively in the food industry for the production of food enzymes such as pectinase and food additives such as citric acid. They are used in the production of fermented foods such as alcoholic drinks, bread, cheese, and soy sauce. More than a dozen species of mushrooms are used as foods directly. Many of our most important antibiotics, such as penicillin, cyclosporin, and lovastatin, come from fungi. Fungi also have many negative impacts on human health and economics. Fungi are serious pathogens in immuno-compromised patients. Fungi are the single largest group of plant pathogens and thus a serious limit on crop productivity throughout the world. Many fungi are allergenic, and mold contamination of residences and commercial buildings is now recognized as a serious public health threat. As decomposers, fungi cause extensive damage to just about all natural and synthetic materials.

  17. Molecular genetics and clinical applications for RH

    OpenAIRE

    Flegel, Willy A.

    2011-01-01

    Rhesus is the clinically most important protein-based blood group system. It represents the largest number of antigens and the most complex genetics of the 30 known blood group systems. The RHD and RHCE genes are strongly homologous. Some genetic complexity is explained by their close chromosomal proximity and unusual orientation, with their tail ends facing each other. The antigens are expressed by the RhD and the RhCE proteins. Rhesus exemplifies the correlation of genotype and phenotype, f...

  18. 76 FR 72957 - 4th Annual Trauma Spectrum Conference: Bridging the Gap Between Research and Clinical Practice of...

    Science.gov (United States)

    2011-11-28

    ... HUMAN SERVICES National Institutes of Health 4th Annual Trauma Spectrum Conference: Bridging the Gap... Annual Trauma Spectrum Conference: Bridging the Gap Between Research and Clinical Practice of... conference information, visit the Trauma Spectrum Conference Web site at...

  19. Palmoplantar keratodermas: clinical and genetic aspects.

    Science.gov (United States)

    Has, Cristina; Technau-Hafsi, Kristin

    2016-02-01

    Palmoplantar keratodermas comprise a diverse group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Early onset and positive family history suggest a genetic cause. While hereditary forms of palmoplantar keratoderma (PPK) may represent the sole or dominant clinical feature, they may also be associated with other ectodermal defects or extracutaneous manifestations. In recent years, much progress has been made in deciphering the genetic basis of PPK, which has led to the emergence of new disorders and syndromes. The elucidation of disease mechanisms has opened new avenues for specific therapies, increasingly sparking interest in this field. Given the high heterogeneity with respect to clinical features, genetic defects, and disease mechanisms, the classification of PPK is based on various criteria. These include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis. Though not always feasible, the clinical distinction of various PPK entities is based on fine-tuned criteria or clues. Remarkably, apparently distinct disorders have been shown to be allelic, as they are caused by mutations in the same gene. By contrast, similar clinical pictures may result from mutations in different genes. Because of this complexity, mutation analysis is required to determine the precise type of PPK. The best-defined entities are described in this review. PMID:26819106

  20. Primary ciliary dyskinesia: clinical and genetic aspects

    Directory of Open Access Journals (Sweden)

    E. D’Auria

    2012-06-01

    Full Text Available Primary ciliary dyskinesia (PCD is a rare, genetically heterogeneous disease, characterized by ciliary disfunction and impaired mucociliary clearance, resulting in a range of clinical manifestations such as chronic bronchitis, bronchiectasis, chronic rhino-sinusitis, chronic otitis media, situs viscerum inversus in almost 40-50% of cases and male infertility. The triad situs viscerum inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. Up to now little is known about genetic, diagnostic and therapeutic aspects of primary motile ciliary diseases in children: for this reason, diagnosis is generally delayed and almost all treatments for PCD are not based on randomized studies but extrapolated from cystic fibrosis guidelines. The aim of this review is to propose to pediatricians a summary of current clinical and diagnostic evidence to obtain better knoledwge of this condition. The earlier diagnosis and the right treatment are both crucial to improve the prognosis of PCD.

  1. Clinical Genetic Testing of Periodic Fever Syndromes

    Directory of Open Access Journals (Sweden)

    Annalisa Marcuzzi

    2013-01-01

    Full Text Available Periodic fever syndromes (PFSs are a wide group of autoinflammatory diseases. Due to some clinical overlap between different PFSs, differential diagnosis can be a difficult challenge. Nowadays, there are no universally agreed recommendations for most PFSs, and near half of patients may remain without a genetic diagnosis even after performing multiple-gene analyses. Molecular analysis of periodic fevers’ causative genes can improve patient quality of life by providing early and accurate diagnosis and allowing the administration of appropriate treatment. In this paper we focus our discussion on effective usefulness of genetic diagnosis of PFSs. The aim of this paper is to establish how much can the diagnostic system improve, in order to increase the success of PFS diagnosis. The mayor expectation in the near future will be addressed to the so-called next generation sequencing approach. Although the application of bioinformatics to high-throughput genetic analysis could allow the identification of complex genotypes, the complexity of this definition will hardly result in a clear contribution for the physician. In our opinion, however, to obtain the best from this new development a rule should always be kept well in mind: use genetics only to answer specific clinical questions.

  2. [Clinical aspects and genetics of pseudoxanthoma elasticum].

    Science.gov (United States)

    Stutz, S B; Schnyder, U W; Vogel, A

    1985-05-01

    Eighteen cases of Pseudoxantoma elasticum (PXE) were analysed using clinical and genetic criteria. We observed great intra- and interfamiliar variations in the manifestations of the disease as well as mono-, bi- and trisymptomatic cases (skin + eyes + vessels). We lack reliable indications for the existence of more than one recessive type of PXE and hence for heterogeneity. In family 9, PXE was inherited in an autosomal-dominant mode, and the discrete symptoms were restricted to the skin. PMID:4008253

  3. Currently Clinical Views on Genetics of Wilson′s Disease

    Directory of Open Access Journals (Sweden)

    Chen Chen

    2015-01-01

    Conclusions: Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype. Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gene therapy for WD patients.

  4. International conference. The problems of radiation genetics at the turn of the century. Abstracts

    International Nuclear Information System (INIS)

    Information concerning International conference: The problems of radiation genetics at the turn of the century - held in Moscow, November, 2000, is presented. The conference is dedicated to the memory of Timofeev-Resovsky (centenary of birth). Analysis of the development of concepts of the radiation genetics founder concerning study of genetic radiation effects on plants, animals and man is given. Molecular-genetic mechanisms of radiation mutagenesis are considered. Problems related to the analysis of delayed genetic radiation effects on the different types. Populations and regularities in radiation-induced mutagenesis at cellular, tissue and body levels are discussed. Great attention is paid to the genetic consequences for population, flora and fauna of Chernobyl and Kyshtym accidents, nuclear explosions at Semipalatinsk test site and other emergency radiation situations

  5. Autism spectrum disorder genetics: diverse genes with diverse clinical outcomes.

    Science.gov (United States)

    Talkowski, Michael E; Minikel, Eric Vallabh; Gusella, James F

    2014-01-01

    The last several years have seen unprecedented advances in deciphering the genetic etiology of autism spectrum disorders (ASDs). Heritability studies have repeatedly affirmed a contribution of genetic factors to the overall disease risk. Technical breakthroughs have enabled the search for these genetic factors via genome-wide surveys of a spectrum of potential sequence variations, from common single-nucleotide polymorphisms to essentially private chromosomal abnormalities. Studies of copy-number variation have identified significant roles for both recurrent and nonrecurrent large dosage imbalances, although they have rarely revealed the individual genes responsible. More recently, discoveries of rare point mutations and characterization of balanced chromosomal abnormalities have pinpointed individual ASD genes of relatively strong effect, including both loci with strong a priori biological relevance and those that would have otherwise been unsuspected as high-priority biological targets. Evidence has also emerged for association with many common variants, each adding a small individual contribution to ASD risk. These findings collectively provide compelling empirical data that the genetic basis of ASD is highly heterogeneous, with hundreds of genes capable of conferring varying degrees of risk, depending on their nature and the predisposing genetic alteration. Moreover, many genes that have been implicated in ASD also appear to be risk factors for related neurodevelopmental disorders, as well as for a spectrum of psychiatric phenotypes. While some ASD genes have evident functional significance, like synaptic proteins such as the SHANKs, neuroligins, and neurexins, as well as fragile x mental retardation-associated proteins, ASD genes have also been discovered that do not present a clear mechanism of specific neurodevelopmental dysfunction, such as regulators of chromatin modification and global gene expression. In its sum, the progress from genetic studies to date

  6. June 6—7, 2011 Clinical Trials Conference: New Challenges & Opportunities | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... please turn Javascript on. June 6–7, 2011 Clinical Trials Conference: New Challenges & Opportunities Past Issues / Spring 2011 ... pressing issues in clinical trials, including: Support the Clinical Trials Conference If you or your organization would like ...

  7. Technical conference of the section 'Genetic Engineering and Environmental Protection'

    International Nuclear Information System (INIS)

    This conference was held on 13 November 2000 by the GSF Research Centre for Ecology and Health on behalf of the Bavarian State Minister of Regional Development and the Environment. It was attended by about 50 scientists working in this field and 50 representatives of universities and other scientific institutions, who presented new findings of their research projects. (orig.)

  8. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma

    Science.gov (United States)

    Van Allen, Eliezer M.; Wagle, Nikhil; Sucker, Antje; Treacy, Daniel; Johannessen, Cory; Goetz, Eva M.; Place, Chelsea S.; Taylor-Weiner, Amaro; Whittaker, Steven; Kryukov, Gregory; Hodis, Eran; Rosenberg, Mara; McKenna, Aaron; Cibulskis, Kristian; Farlow, Deborah; Zimmer, Lisa; Hillen, Uwe; Gutzmer, Ralf; Goldinger, Simone M.; Ugurel, Selma; Gogas, Helen J.; Egberts, Friederike; Berking, Carola; Trefzer, Uwe; Loquai, Carmen; Weide, Benjamin; Hassel, Jessica C.; Gabriel, Stacey B.; Carter, Scott L.; Getz, Gad; Garraway, Levi A.; Schadendorf, Dirk

    2013-01-01

    Most patients with BRAFV600 metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole exome sequencing on formalin-fixed, paraffin embedded (FFPE) tumors from 45 patients with BRAFV600 metastatic melanoma who received vemurafenib or dabrafenib monotherapy. Genetic alterations in known or putative RAF inhibitor resistance genes were observed in 23 of 45 patients (51%). Besides previously characterized alterations, we discovered a “long tail” of new MAPK pathway alterations (MAP2K2, MITF) that confer RAF inhibitor resistance. In three cases, multiple resistance gene alterations were observed within the same tumor biopsy. Overall, RAF inhibitor therapy leads to diverse clinical genetic resistance mechanisms, mostly involving MAPK pathway reactivation. Novel therapeutic combinations may be needed to achieve durable clinical control of BRAFV600 melanoma. Integrating clinical genomics with preclinical screens may model subsequent resistance studies. PMID:24265153

  9. An everlasting role of genetics and genomics in public health: a meeting report of ACGA-HKSMG International Conference on Genetic and Genomic Medicine 2008

    Institute of Scientific and Technical Information of China (English)

    Wai-Yee Chan; Stephen T.S.Lam; Bai-Lin Wu

    2009-01-01

    @@ The Association of Chinese Geneticists in America (ACGA) and the Hong Kong Society of Medical Genetics (HKSMG) held their first joint Conference on Genetic and Genomic Medicine in Hong Kong from June 9-11 in 2008at the Cheung Kung Hai Conference Center, William MW Mong Block, Li Ka Shing Faculty of Medicine, the University of Hong Kong.

  10. FASEB Summer Research Conference. Genetic Recombination and Chromosome Rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Jinks-Robertson, Sue

    2002-02-01

    The 2001 meeting entitled ''Genetic Recombination and Genome Rearrangements'' was held July 21-26 in Snowmass, Colorado. The goal of the meeting was to bring together scientists using diverse approaches to study all aspects of genetic recombination. This goal was achieved by integrating talks covering the genetics, biochemistry and structural biology of homologous recombination, site-specific recombination, and nonhomologous recombination. The format of the meeting consisted of a keynote address on the opening evening, two formal plenary sessions on each of the four full meeting days, a single afternoon workshop consisting of short talks chosen from among submitted abstracts, and afternoon poster sessions on each of the four full meeting days. The eight plenary session were entitled: (1) Recombination Mechanisms, (2) Prokaryotic Recombination, (3) Repair and Recombination, (4) Site-specific Recombination and Transposition, (5) Eukaryotic Recombination I, (6) Genome Rearrangements, (7) Meiosis, and (8) Eukaryotic Recombination II. Each session included a mix of genetic, biochemical and structural talks; talks were limited to 20 minutes, followed by 10 minutes of very lively, general discussion. Much of the data presented in the plenary sessions was unpublished, thus providing attendees with the most up-to-date knowledge of this rapidly-moving field.

  11. A Case Based Approach to Clinical Genetics of Thoracic Aortic Aneurysm/Dissection

    Directory of Open Access Journals (Sweden)

    Betti Giusti

    2016-01-01

    Full Text Available Thoracic aortic aneurysm/dissection (TAAD is a potential lethal condition with a rising incidence. This condition may occur sporadically; nevertheless, it displays familial clustering in >20% of the cases. Family history confers a six- to twentyfold increased risk of TAAD and has to be considered in the identification and evaluation of patients needing an adequate clinical follow-up. Familial TAAD recognizes a number of potential etiologies with a significant genetic heterogeneity, in either syndromic or nonsyndromic forms of the manifestation. The clinical impact and the management of patients with TAAD differ according to the syndromic and nonsyndromic forms of the manifestation. The clinical management of TAAD patients varies, depending on the different forms. Starting from the description of patient history, in this paper, we summarized the state of the art concerning assessment of clinical/genetic profile and therapeutic management of TAAD patients.

  12. A Case Based Approach to Clinical Genetics of Thoracic Aortic Aneurysm/Dissection.

    Science.gov (United States)

    Giusti, Betti; Nistri, Stefano; Sticchi, Elena; De Cario, Rosina; Abbate, Rosanna; Gensini, Gian Franco; Pepe, Guglielmina

    2016-01-01

    Thoracic aortic aneurysm/dissection (TAAD) is a potential lethal condition with a rising incidence. This condition may occur sporadically; nevertheless, it displays familial clustering in >20% of the cases. Family history confers a six- to twentyfold increased risk of TAAD and has to be considered in the identification and evaluation of patients needing an adequate clinical follow-up. Familial TAAD recognizes a number of potential etiologies with a significant genetic heterogeneity, in either syndromic or nonsyndromic forms of the manifestation. The clinical impact and the management of patients with TAAD differ according to the syndromic and nonsyndromic forms of the manifestation. The clinical management of TAAD patients varies, depending on the different forms. Starting from the description of patient history, in this paper, we summarized the state of the art concerning assessment of clinical/genetic profile and therapeutic management of TAAD patients. PMID:27314043

  13. A Case Based Approach to Clinical Genetics of Thoracic Aortic Aneurysm/Dissection

    Science.gov (United States)

    Giusti, Betti; Nistri, Stefano; Sticchi, Elena; De Cario, Rosina; Abbate, Rosanna; Gensini, Gian Franco; Pepe, Guglielmina

    2016-01-01

    Thoracic aortic aneurysm/dissection (TAAD) is a potential lethal condition with a rising incidence. This condition may occur sporadically; nevertheless, it displays familial clustering in >20% of the cases. Family history confers a six- to twentyfold increased risk of TAAD and has to be considered in the identification and evaluation of patients needing an adequate clinical follow-up. Familial TAAD recognizes a number of potential etiologies with a significant genetic heterogeneity, in either syndromic or nonsyndromic forms of the manifestation. The clinical impact and the management of patients with TAAD differ according to the syndromic and nonsyndromic forms of the manifestation. The clinical management of TAAD patients varies, depending on the different forms. Starting from the description of patient history, in this paper, we summarized the state of the art concerning assessment of clinical/genetic profile and therapeutic management of TAAD patients. PMID:27314043

  14. MMP-9 genetic polymorphism may confer susceptibility to COPD.

    Science.gov (United States)

    Jiang, S; Yang, Z H; Chen, Y Y; He, Z; Zhou, Y; Gao, Y; Zhang, Q; Tan, M Q

    2016-01-01

    Correlations between genetic polymorphisms of three matrix metalloproteinase (MMP) genes and susceptibility to chronic obstructive pulmonary disease (COPD) were investigated. Relevant case-control studies were selected using rigorous inclusion and exclusion criteria. The comprehensive Meta-analysis 2.0 software was used to conduct the statistical analysis. An odds ratio with 95% confidence intervals was applied to assess the correlation between genetic polymorphisms of MMPs and susceptibility to COPD. Twelve high-quality studies were selected for inclusion in this meta-analysis. These studies included a combined total of 1533 COPD patients and 1530 healthy controls. The result of the meta-analysis showed that MMP-9 rs3918242 C > T was significantly correlated with increased susceptibility to COPD. However, MMP-1 rs1799750 1G > 2G and MMP-3 rs3025058 5A > 6A were not associated with COPD risk (all P > 0.05). Based on our meta-analysis, MMP-9 rs3918242 C > T is correlated with susceptibility to COPD, but MMP-1 rs1799750 1G > 2G and MMP-3 rs3025058 5A > 6A are not. These results should be further confirmed using a larger sample size. PMID:27173221

  15. Negative feedback in genetic circuits confers evolutionary resilience and capacitance.

    Science.gov (United States)

    Marciano, David C; Lua, Rhonald C; Katsonis, Panagiotis; Amin, Shivas R; Herman, Christophe; Lichtarge, Olivier

    2014-06-26

    Natural selection for specific functions places limits upon the amino acid substitutions a protein can accept. Mechanisms that expand the range of tolerable amino acid substitutions include chaperones that can rescue destabilized proteins and additional stability-enhancing substitutions. Here, we present an alternative mechanism that is simple and uses a frequently encountered network motif. Computational and experimental evidence shows that the self-correcting, negative-feedback gene regulation motif increases repressor expression in response to deleterious mutations and thereby precisely restores repression of a target gene. Furthermore, this ability to rescue repressor function is observable across the Eubacteria kingdom through the greater accumulation of amino acid substitutions in negative-feedback transcription factors compared to genes they control. We propose that negative feedback represents a self-contained genetic canalization mechanism that preserves phenotype while permitting access to a wider range of functional genotypes. PMID:24910431

  16. PREFACE: XVII Congress of Bioengineering and VI Clinical Engineering Conference

    Science.gov (United States)

    Rocha, Darío

    2011-09-01

    SABI 2009 was the XVII Biennial Congress of the Argentinean Bioengineering Society (SABI - www.sabi.org.ar), celebrated along with the VI Clinical Engineering Conference. It took place in Rosario, the second city of Argentina, located on the west bank of the Paraná, one of the world's most important rivers. This city, with its 150 year history and one million inhabitants, is characterized by a strong enterprising spirit. It is the agroindustrial leader of Argentina, with cereal ports recognized to be among the most active in the world, and its cereal stock exchange competes with Chicago's in international cereal pricing. Demographically Rosario presents a European profile, and there are seven national and private higher level universities in the area. SABI 2009 was the first time the Congress was celebrated in Rosario. Usually the Congress is organized by the Bioengineering Society in cooperation with a university with an undergraduate program, which Rosario lacks. To meet the needs of this exceptional case, a young local institution was asked to coordinate the Congress, the Rosario Technological Center (www.polotecnologico.net). This organization gathers together around 100 companies that produce technology, with a large number focused on IT, but those focused on biotechnology also stand out. The Center is also integrated with relevant public and government bodies. Traditionally, bioengineering has been related to human health applications, with less emphasis on applications significant to agrotechnology, an area in which Rosario is growing as an economic force. In order to address this oversight, the Congress formulated its main goals for integrating and synergizing bioengineering and biotechnology, particularly bioengineering and agrotechnology. This initiative has produced promising results. The importance of the Congress was reflected in the high number of participants - including researchers, professionals and students - from abroad, with participants from

  17. Genetic transformation of deciduous fruit trees conferring resistance against diseases

    International Nuclear Information System (INIS)

    Long breeding cycles make cultivar development a lengthy process in deciduous fruit species. Gene transfer is, accordingly, a goal with significant commercial value. In many plant species, especially in woody plants, a prerequisite for genetic engineering is the ability to regenerate plants from transformed cells. Development of single cell regeneration is the first step towards exploration of gene transfer techniques. In this investigation media for plum and apple leaf disk regeneration were developed. Transformation experiments were performed. The vector EHA105 containing the gus-intron gene was found to be effective for gene transfer. Induction of the virG genes with aceto-syringone did not enhance transformation. Cefotaxime that was supplemented in the plum selection medium to suppress the Agrobacterium vector seriously inhibited leaf disk regeneration. However, in applies it was not detrimental. With further apple transformation experiments, factors such as preculturing, age of leaves, sucrose and cefotaxime concentrations did not increase the transformation efficiency of the marker gene. The harpin protein, essential for the pathogenicity of Pseudomonas syringae pv. syringae which incites bacterial canker of stone fruit, ws amplified and cloned into an expression vector. The fusion protein was purified. This will be used in future studies to elucidate the host-pathogen interaction, and to identify antibacterial genes. (author)

  18. Genetic Characteristics of Glioblastoma: Clinical Implications of Heterogeneity

    Directory of Open Access Journals (Sweden)

    Qian Li

    2015-01-01

    Full Text Available Glioblastoma multiforme (GBM is a heterogeneous group of tumors, each with its own distinct molecular and genetic signatures. This heterogeneity is a major clinical hurdle for classifying tumors and for devising effective personalized therapies targeting the disease pathways. Herein, the primary genetic and epigenetic alterations in GBM that have been used as therapeutic targets in clinical settings nowadays, with or without clinical benefits for patients, as well as the future directions for developing novel strategies were discussed.

  19. Genetics and the clinical approach to paragangliomas.

    Science.gov (United States)

    Schulte, K-M; Talat, N; Galata, G; Aylwin, S; Izatt, L; Eisenhofer, G; Barthel, A; Bornstein, S R

    2014-12-01

    This study analyses new information on gene mutations in paragangliomas and puts them into a clinical context. A suspicion of malignancy is critical to determine the workup and surgical approach in adrenal (A-PGL) and extra-adrenal (E-PGL) paragangliomas (PGLs). Malignancy rates vary with location, family history, and gene tests results. Currently there is no algorithm incorporating the above information for clinical use. A sum of 1,821 articles were retrieved from PubMed using the search terms "paraganglioma genetics". Thirty-seven articles were selected of which 9 were analyzed. It was found that 599/2,487 (24%) patients affected with paragangliomas had a germline mutation. Of these 30.2% were mutations in SDHB, 25% VHL, 19.4% RET, 18.4% SDHD, 5.0% NF1, and 2.0% SDHC genes. A family history was positive in 18.1-64.3% of patients. Adrenal PGLs accounted for 55.1% in mutation (+) and 81.0% in mutation (-) patients (RR 1.2, p < 0.0001). Bilateral A-PGLs accounted for 56.4% in mutation (+) and 3.2% in mutation (-) patients (RR 8.7, p < 0.0001). E-PGL were found in 33.6% of mut+ and 17.3% of mut- (RR 1.7, p < 0.0001). In mutation (+) patients PGLs malignancy varied with location, adrenal (6.4%) thoraco-abdominal E-PGL (38%), H & N E-PGL (10%). Malignancy rates were 8.2% in mutation (-) and lower in mutation (+) PGLs except for SDHB 36.5% and SDHC 8.3%. Exclusion of a mutation lowered the probability of malignancy significantly in E-PGL (RR 0.03 (95% CI 0.1-0.6); p < 0.001). Mutation analysis provides valuable preoperative information to assess the risk of malignancy in A-PG and E-PGLs and should be considered in the work up of all E-PGL lesions. PMID:25014332

  20. 13th AINSE radiation biology conference: conference handbook

    International Nuclear Information System (INIS)

    The forty one papers presented at this conference covered the areas of radiation induced lesions, apoptosis, genetics and radiobiological consequences of low level radiation exposure, clinical applications of radiation, mammalian cells radiosensitivity and radiation-activated proteins

  1. PREFACE: XVII Congress of Bioengineering and VI Clinical Engineering Conference

    Science.gov (United States)

    Rocha, Darío

    2011-09-01

    SABI 2009 was the XVII Biennial Congress of the Argentinean Bioengineering Society (SABI - www.sabi.org.ar), celebrated along with the VI Clinical Engineering Conference. It took place in Rosario, the second city of Argentina, located on the west bank of the Paraná, one of the world's most important rivers. This city, with its 150 year history and one million inhabitants, is characterized by a strong enterprising spirit. It is the agroindustrial leader of Argentina, with cereal ports recognized to be among the most active in the world, and its cereal stock exchange competes with Chicago's in international cereal pricing. Demographically Rosario presents a European profile, and there are seven national and private higher level universities in the area. SABI 2009 was the first time the Congress was celebrated in Rosario. Usually the Congress is organized by the Bioengineering Society in cooperation with a university with an undergraduate program, which Rosario lacks. To meet the needs of this exceptional case, a young local institution was asked to coordinate the Congress, the Rosario Technological Center (www.polotecnologico.net). This organization gathers together around 100 companies that produce technology, with a large number focused on IT, but those focused on biotechnology also stand out. The Center is also integrated with relevant public and government bodies. Traditionally, bioengineering has been related to human health applications, with less emphasis on applications significant to agrotechnology, an area in which Rosario is growing as an economic force. In order to address this oversight, the Congress formulated its main goals for integrating and synergizing bioengineering and biotechnology, particularly bioengineering and agrotechnology. This initiative has produced promising results. The importance of the Congress was reflected in the high number of participants - including researchers, professionals and students - from abroad, with participants from

  2. Fibrodysplasia Ossificans Progressiva: Clinical and Genetic Aspects

    Directory of Open Access Journals (Sweden)

    Pignolo Robert J

    2011-12-01

    Full Text Available Abstract Fibrodysplasia ossificans progressiva (FOP is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites. The worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. Children who have FOP appear normal at birth except for congenital malformations of the great toes. During the first decade of life, sporadic episodes of painful soft tissue swellings (flare-ups occur which are often precipitated by soft tissue injury, intramuscular injections, viral infection, muscular stretching, falls or fatigue. These flare-ups transform skeletal muscles, tendons, ligaments, fascia, and aponeuroses into heterotopic bone, rendering movement impossible. Patients with atypical forms of FOP have been described. They either present with the classic features of FOP plus one or more atypical features [FOP plus], or present with major variations in one or both of the two classic defining features of FOP [FOP variants]. Classic FOP is caused by a recurrent activating mutation (617G>A; R206H in the gene ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP type I receptor. Atypical FOP patients also have heterozygous ACVR1 missense mutations in conserved amino acids. The diagnosis of FOP is made by clinical evaluation. Confirmatory genetic testing is available. Differential diagnosis includes progressive osseous heteroplasia, osteosarcoma, lymphedema, soft tissue sarcoma, desmoid tumors, aggressive juvenile fibromatosis, and non-hereditary (acquired heterotopic ossification. Although most cases of FOP are sporadic (noninherited mutations, a small number of inherited FOP cases show germline transmission in an autosomal dominant pattern. At present, there is no definitive

  3. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era

    Directory of Open Access Journals (Sweden)

    Costain G

    2012-02-01

    Full Text Available Gregory Costain1,2, Anne S Bassett1–41Clinical Genetics Research Program, Centre for Addiction and Mental Health, 2Institute of Medical Science, University of Toronto, 3Division of Cardiology, Department of Medicine and Department of Psychiatry, University Health Network, 4Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadaAbstract: Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.Keywords: schizophrenia, genetics, 22q11 deletion syndrome, copy number variation, genetic counseling, genetic predisposition to disease

  4. Genetic engineering in insects: Cloning and transformation of genes conferring resistance to insecticides

    International Nuclear Information System (INIS)

    Genetic engineering and transformation offer the possibility of modifying the genetic material of insects. These techniques will make it possible, for example, to transfer genes conferring resistance to insecticides into the genome of beneficial species, or to develop new methods of combating insect pests and disease carrying insects. We cloned two genes which contain the code for proteins that detoxify insecticides. The first, esterase B1 from Culex quinquefasciatus, is amplified approximately 250 times in Californian mosquitoes resistant to organic phosphate insecticides. A second esterase gene was cloned from bacteria which break down various organic phosphates. Experiments are in progress to transfer these genes to Drosophila and beneficial insects. These same genes could also serve as selection markers for the purpose of developing transformation techniques for different insects whose genome one wishes to modify using genetic engineering techniques. (author). 5 refs

  5. Genetic and Clinical Investigation of Noonan Spectrum Disorders

    OpenAIRE

    Ekvall, Sara

    2012-01-01

    Noonan spectrum disorders belong to the RASopathies, a group of clinically related developmental disorders caused by dysregulation of the RAS-MAPK pathway. This thesis describes genetic and clinical investigations of six families with Noonan spectrum disorders. In the first family, the index patient presented with severe Noonan syndrome (NS) and multiple café-au-lait (CAL) spots, while four additional family members displayed multiple CAL spots only. Genetic analysis of four RAS-MAPK genes re...

  6. Mitochondrial DNA Haplogroup A may confer a genetic susceptibility to AIDS group from Southwest China.

    Science.gov (United States)

    Wang, Hua-Wei; Xu, Yu; Miao, Ying-Lei; Luo, Hua-You; Wang, Kun-Hua

    2016-05-01

    The acquired immunodeficiency syndrome (AIDS) in humans was one of the chronic infections caused by human immunodeficiency virus (HIV), and the interactions between viral infection and mitochondrial energetic implicated that mitochondrial DNA (mtDNA) variation(s) may effect genetic susceptibility to AIDS. Thus, to illustrate the maternal genetic structure and further identify whether mtDNA variation(s) can effect HIV infection among southwest Chinese AIDS group, the whole mtDNA control region sequences of 70 AIDS patients and 480 health individuals from southwest China were analyzed here. Our results indicated the plausible recent genetic admixture results of AIDS group; comparison of matrilineal components between AIDS and matched Han groups showed that mtDNA haplogroup A (p = 0.048, OR = 3.006, 95% CI = 1.109-8.145) has a significant higher difference between the two groups; further comparison illustrated that mtDNA mutations 16,209 (p = 0.046, OR = 2.607, 95% CI = 0.988-6.876) and 16,319 (p = 0.009, OR = 2.965, 95% CI = 1.278-6.876) have significant differences between AIDS and matched control groups, and both of which were the defining variations of mtDNA haplogroup A, they further confirmed that mtDNA haplogroup A may confer genetic susceptibility to AIDS. Our results suggested that haplogroup A may confer a genetic susceptibility to AIDS group from Southwest China. PMID:25431816

  7. Currently Clinical Views on Genetics of Wilson's Disease

    Institute of Scientific and Technical Information of China (English)

    Chen Chen; Bo Shen; Jia-Jia Xiao; Rong Wu; Sarah Jane Duff Canning; Xiao-Ping Wang

    2015-01-01

    Objective:The objective of this study was to review the research on clinical genetics of Wilson's disease (WD).Data Sources:We searched documents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic,ATP7B gene,gene mutation,genotype,phenotype.Study Selection:Publications about the ATP7B gene and protein function associated with clinical features were selected.Results:Wilson's disease,also named hepatolenticular degeneration,is an autosomal recessive genetic disorder characterized by abnormal copper metabolism caused by mutations to the copper-transporting gene A TP7B.Decreased biliary copper excretion and reduced incorporation of copper into apoceruloplasmin caused by defunctionalization of ATP7B protein lead to accumulation of copper in many tissues and organs,including liver,brain,and cornea,finally resulting in liver disease and extrapyramidal symptoms.It is the most common genetic neurological disorder in the onset of adolescents,second to muscular dystrophy in China.Early diagnosis and medical therapy are of great significance for improving the prognosis of WD patients.However,diagnosis of this disease is usually difficult because of its complicated phenotypes.In the last 10 years,an increasing number of clinical studies have used molecular genetics techniques.Improved diagnosis and prediction of the progression of this disease at the molecular level will aid in the development of more individualized and effective interventions,which is a key to transition from molecular genetic research to the clinical study.Conclusions:Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype.Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gene therapy for WD patients.

  8. Genetics of Cystic Fibrosis: Clinical Implications.

    Science.gov (United States)

    Egan, Marie E

    2016-03-01

    Cystic fibrosis (CF) is a common life-shortening autosomal recessive genetic disorder caused by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). Almost 2000 variants in the CFTR gene have been identified. The mutational classes are based on the functional consequences on CFTR. New therapies are being developed to target mutant CFTR and restore CFTR function. Understanding specific CF genotypes is essential for providing state-of-the art care to patients. In addition to the variation in CFTR genotype, there are several modifier genes that contribute to the respiratory phenotype. PMID:26857764

  9. The genetic landscape of Alzheimer disease: clinical implications and perspectives

    Science.gov (United States)

    Van Cauwenberghe, Caroline; Van Broeckhoven, Christine; Sleegers, Kristel

    2016-01-01

    The search for the genetic factors contributing to Alzheimer disease (AD) has evolved tremendously throughout the years. It started from the discovery of fully penetrant mutations in Amyloid precursor protein, Presenilin 1, and Presenilin 2 as a cause of autosomal dominant AD, the identification of the ɛ4 allele of Apolipoprotein E as a strong genetic risk factor for both early-onset and late-onset AD, and evolved to the more recent detection of at least 21 additional genetic risk loci for the genetically complex form of AD emerging from genome-wide association studies and massive parallel resequencing efforts. These advances in AD genetics are positioned in light of the current endeavor directing toward translational research and personalized treatment of AD. We discuss the current state of the art of AD genetics and address the implications and relevance of AD genetics in clinical diagnosis and risk prediction, distinguishing between monogenic and multifactorial AD. Furthermore, the potential and current limitations of molecular reclassification of AD to streamline clinical trials in drug development and biomarker studies are addressed. Genet Med 18 5, 421–430. PMID:26312828

  10. Carney complex: Clinical and genetic 2010 update.

    Science.gov (United States)

    Vezzosi, D; Vignaux, O; Dupin, N; Bertherat, J

    2010-12-01

    First described in the mid 1980s, Carney complex is a rare dominantly heritable multiple endocrine neoplasia syndrome that affects endocrine glands as the adrenal cortex, the pituitary and the thyroid. It is associated with many other nonendocrine tumors, including cardiac myxomas, testicular tumors, melanotic schwannoma, breast myxomatosis, and abnormal pigmentation or myxomas of the skin. The Carney complex gene 1 was identified 10 years ago as the regulatory subunit 1A of protein kinase A (PRKAR1A) located at 17q22-24. An inactivating heterozygous germ line mutation of PRKAR1A is observed in about two-thirds of Carney complex patients. This last decade many progresses have been done in the knowledge of this rare disease and its genetics. This review outlines the current state of this knowledge on Carney complex. PMID:20850710

  11. Biotinidase deficiency: clinical and genetic studies of 38 Brazilian patients

    OpenAIRE

    Borsatto, Taciane; Sperb-Ludwig, Fernanda; Pinto, Louise LC; De Luca, Gisele R; Carvalho, Francisca L; De Souza, Carolina FM; De Medeiros, Paula FV; Charles M. Lourenço; Filho, Reinaldo LO; Neto, Eurico C.; Bernardi, Pricila; Leistner-Segal, Sandra; Schwartz, Ida VD

    2014-01-01

    Background Biotinidase deficiency (BD) is an inborn error of metabolism in which some genetic variants correlate with the level of enzyme activity. Biotinidase activity, however, may be artifactually low due to enzyme lability, premature birth, and jaundice; this hinders both phenotypic classification and the decision to implement therapy. This study sought to characterize the clinical and genetic profile of a sample of Brazilian patients exhibiting reduced biotinidase activity. Methods This ...

  12. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Gammon A

    2016-07-01

    Full Text Available Amanda Gammon,1 Kory Jasperson,1,2 Marjan Gammon11Huntsman Cancer Institute Family Cancer Assessment Clinic Salt Lake City, UT, USA; 2Ambry Genetics Medical Affairs Aliso Viejo, CA USAAbstract: Cowden syndrome (CS is an often difficult to recognize hereditary cancer predisposition syndrome caused by mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN. In addition to conferring increased cancer risks, CS also predisposes individuals to developing hamartomatous growths in many areas of the body. Due to the rarity of CS, estimates vary on the penetrance of certain phenotypic features, such as macrocephaly and skin findings (trichilemmomas, mucocutaneous papules, as well as the conferred lifetime cancer risks. To address this variability, separate clinical diagnostic criteria and PTEN testing guidelines have been created to assist clinicians in the diagnosis of CS. As knowledge of CS increases, making larger studies of affected patients possible, these criteria continue to be refined. Similarly, the management guidelines for cancer screening and risk reduction in patients with CS continue to be updated. This review will summarize the current literature on CS to assist clinicians in staying abreast of recent advances in CS knowledge, diagnostic approaches, and management.Keywords: Cowden syndrome, PTEN gene, hereditary cancer, genetic counseling

  13. Changes in Emotion Work at Interdisciplinary Conferences Following Clinical Supervision in a Palliative Outpatient Ward

    DEFF Research Database (Denmark)

    Nordentoft, Helle Merete

    2008-01-01

    In this article, I describe changes in emotion work at weekly interdisciplinary conferences in a palliative1 outpatient ward following clinical supervision (CS). I conceive emotions as constantly negotiated in interaction, and I researched the similarity between how this is done during CS and at ...... conclude that CS enhances professional development and may prevent burnout in palliative care....

  14. Oligocone trichromacy: clinical and molecular genetic investigations

    DEFF Research Database (Denmark)

    Andersen, Mette K G; Christoffersen, Nynne L B; Sander, Birgit; Edmund, Carsten; Larsen, Michael; Grau, Tanja; Wissinger, Bernd; Kohl, Susanne; Rosenberg, Thomas

    2010-01-01

    PURPOSE: To describe the phenotype and genotype of patients with a diagnosis of oligocone trichromacy (OT). METHODS: Six unrelated patients had a detailed ophthalmic examination including color vision testing, a Goldmann visual field test, fundus photography, and full-field electroretinography (ff...... congenital nystagmus, and subjectively normal or near-normal color vision; five patients reported photophobia. Clinical examinations revealed largely normal fundi, normal Goldmann visual field results with the IV/4e target, and normal color discrimination or mild color vision deficiency. Electrophysiological...

  15. Genetic relatedness of Trichomonas vaginalis reference and clinical isolates.

    Science.gov (United States)

    Cornelius, Denise C; Mena, Leandro; Lushbaugh, William B; Meade, John C

    2010-12-01

    We have determined the metronidazole susceptibility status of 20 Trichomonas vaginalis isolates from American Type Culture Collection (ATCC) and assessed the level of genetic relatedness in these isolates using 32 additional T. vaginalis clinical isolates for comparison. These ATCC isolates are commonly used as reference strains in T. vaginalis research and this information provides a rational basis for selection of reference strains for use in comparative studies of T. vaginalis phenotypic and clinical characteristics. PMID:21118935

  16. Triploid pregnancies, genetic and clinical features of 158 cases

    DEFF Research Database (Denmark)

    Joergensen, Mette W; Niemann, Isa; Rasmussen, Anders A;

    2014-01-01

    OBJECTIVE: The purpose of this study was to analyze the correlation between the genetic constitution and the phenotype in triploid pregnancies. STUDY DESIGN: One hundred fifty-eight triploid pregnancies were identified in hospitals in Western Denmark from April 1986 to April 2010. Clinical data and...

  17. Clinical, biochemical and genetic heterogeneity in lysosomal storage diseases

    NARCIS (Netherlands)

    A.J.J. Reuser (Arnold)

    1977-01-01

    textabstractThe history of lysosomal storage diseases dates back to the end of the last century when the first clinical reports appeared of patients suffering from these genetic, metabolic disorders (Tay, 1881; Gaucher, 1882; Sachs, 1887; Fabry, 1898). About seventy years wouid pass before the term

  18. Genetics of Type 2 Diabetes and Clinical Utility

    Directory of Open Access Journals (Sweden)

    Rajkumar Dorajoo

    2015-06-01

    Full Text Available A large proportion of heritability of type 2 diabetes (T2D has been attributed to inherent genetics. Recent genetic studies, especially genome-wide association studies (GWAS, have identified a multitude of variants associated with T2D. It is thus reasonable to question if these findings may be utilized in a clinical setting. Here we briefly review the identification of risk loci for T2D and discuss recent efforts and propose future work to utilize these loci in clinical setting—for the identification of individuals who are at particularly high risks of developing T2D and for the stratification of specific health-care approaches for those who would benefit most from such interventions.

  19. Genetics of Type 2 Diabetes and Clinical Utility

    Science.gov (United States)

    Dorajoo, Rajkumar; Liu, Jianjun; Boehm, Bernhard O.

    2015-01-01

    A large proportion of heritability of type 2 diabetes (T2D) has been attributed to inherent genetics. Recent genetic studies, especially genome-wide association studies (GWAS), have identified a multitude of variants associated with T2D. It is thus reasonable to question if these findings may be utilized in a clinical setting. Here we briefly review the identification of risk loci for T2D and discuss recent efforts and propose future work to utilize these loci in clinical setting—for the identification of individuals who are at particularly high risks of developing T2D and for the stratification of specific health-care approaches for those who would benefit most from such interventions. PMID:26110315

  20. ClinLabGeneticist: a tool for clinical management of genetic variants from whole exome sequencing in clinical genetic laboratories.

    Science.gov (United States)

    Wang, Jinlian; Liao, Jun; Zhang, Jinglan; Cheng, Wei-Yi; Hakenberg, Jörg; Ma, Meng; Webb, Bryn D; Ramasamudram-Chakravarthi, Rajasekar; Karger, Lisa; Mehta, Lakshmi; Kornreich, Ruth; Diaz, George A; Li, Shuyu; Edelmann, Lisa; Chen, Rong

    2015-01-01

    Routine clinical application of whole exome sequencing remains challenging due to difficulties in variant interpretation, large dataset management, and workflow integration. We describe a tool named ClinLabGeneticist to implement a workflow in clinical laboratories for management of variant assessment in genetic testing and disease diagnosis. We established an extensive variant annotation data source for the identification of pathogenic variants. A dashboard was deployed to aid a multi-step, hierarchical review process leading to final clinical decisions on genetic variant assessment. In addition, a central database was built to archive all of the genetic testing data, notes, and comments throughout the review process, variant validation data by Sanger sequencing as well as the final clinical reports for future reference. The entire workflow including data entry, distribution of work assignments, variant evaluation and review, selection of variants for validation, report generation, and communications between various personnel is integrated into a single data management platform. Three case studies are presented to illustrate the utility of ClinLabGeneticist. ClinLabGeneticist is freely available to academia at http://rongchenlab.org/software/clinlabgeneticist . PMID:26338694

  1. Hereditary anaemias: genetic basis, clinical features, diagnosis, and treatment*

    OpenAIRE

    1982-01-01

    The hereditary anaemias present a major genetic health problem that contributes considerably to childhood mortality and morbidity in many developing countries. This article summarizes recent scientific and technical advances in knowledge concerning the genes involved and their interaction to produce major haemoglobinopathies, the clinical pictures of these conditions, and their diagnostic criteria. Though there is no definitive cure, supportive treatment for the haemoglobinopathies has improv...

  2. Alström Syndrome: Genetics and Clinical Overview

    OpenAIRE

    Marshall, Jan D; Maffei, Pietro; Collin, Gayle B.; Naggert, Jürgen K.

    2011-01-01

    Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinic...

  3. Epidemiological, clinical and genetic aspects of neurofibromatoses in Northern Finland

    OpenAIRE

    Pöyhönen, M. (Minna)

    1999-01-01

    Abstract A population-based study to investigate the epidemiological, genetic and clinical features of neurofibromatoses (NF) in Northern Finland was carried out between 1989–1996. The area concerned was that served by Oulu University Hospital, with a total population of 733 037. A total of 197 patients with neurofibromatosis type 1 (NF1), five with neurofibromatosis type 2 (NF2) and eight with segmental neurofibromatosis (NF5) fulfilling the diagnostic criteria were identified among s...

  4. Genetic Relatedness of Trichomonas vaginalis Reference and Clinical Isolates

    OpenAIRE

    Cornelius, Denise C.; Mena, Leandro; Lushbaugh, William B.; Meade, John C.

    2010-01-01

    We have determined the metronidazole susceptibility status of 20 Trichomonas vaginalis isolates from American Type Culture Collection (ATCC) and assessed the level of genetic relatedness in these isolates using 32 additional T. vaginalis clinical isolates for comparison. These ATCC isolates are commonly used as reference strains in T. vaginalis research and this information provides a rational basis for selection of reference strains for use in comparative studies of T. vaginalis phenotypic a...

  5. Clinical and genetic features of anoctaminopathy in Saudi Arabia

    OpenAIRE

    Bohlega, Saeed; Monies, Dorothy M.; Abulaban, Ahmad A; Murad, Hatem N.; Alhindi, Hindi N.; Meyer, Brian F.

    2015-01-01

    Objectives: Characterization of the phenotypic, pathological, radiological, and genetic findings in 2 Saudi Arabian families with anoctaminopathies, and limb girdle muscular dystrophy type 2L (LGMD2L). Methods: Over a 2-year period from December 2010 to January 2013, the clinical presentations were analyzed and all genes responsible for limb girdle muscular dystrophy (LGMD) were screened in families seen at King Faisal Specialist Hospital and Research Centre, a tertiary care hospital in Riyad...

  6. Dopa-responsive dystonia--clinical and genetic heterogeneity.

    Science.gov (United States)

    Wijemanne, Subhashie; Jankovic, Joseph

    2015-07-01

    Dopa-responsive dystonia (DRD) encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia and exhibit a robust and sustained response to levodopa treatment. Autosomal dominant GTP cyclohydrolase 1 deficiency, also known as Segawa disease, is the most common and best-characterized condition that manifests as DRD, but a similar presentation can be seen with genetic abnormalities that lead to deficiencies in tyrosine hydroxylase, sepiapterin reductase or other enzymes that are involved in the biosynthesis of dopamine. In rare cases, DRD can result from conditions that do not affect the biosynthesis of dopamine; single case reports have shown that DRD can be a manifestation of hereditary spastic paraplegia type 11, spinocerebellar ataxia type 3 and ataxia telangiectasia. This heterogeneity of conditions that underlie DRD frequently leads to misdiagnosis, which delays the appropriate treatment with levodopa. Correct diagnosis at an early stage requires use of the appropriate diagnostic tests, which include a levodopa trial, genetic testing (including whole-exome sequencing), cerebrospinal fluid neurotransmitter analysis, the phenylalanine loading test, and enzyme activity measurements. The selection of tests for use depends on the clinical presentation and level of complexity. This Review presents the common and rarer causes of DRD and their clinical features, and considers the most appropriate approaches to ensure early diagnosis and treatment. PMID:26100751

  7. Clinical and genetic characteristics of craniosynostosis in Hungary.

    Science.gov (United States)

    Bessenyei, Beáta; Nagy, Andrea; Szakszon, Katalin; Mokánszki, Attila; Balogh, Erzsébet; Ujfalusi, Anikó; Tihanyi, Mariann; Novák, László; Bognár, László; Oláh, Éva

    2015-12-01

    Craniosynostosis, the premature closure of cranial sutures, is a common craniofacial disorder with heterogeneous etiology and appearance. The purpose of this study was to investigate the clinical and molecular characteristics of craniosynostoses in Hungary, including the classification of patients and the genetic analysis of the syndromic forms. Between 2006 and 2012, 200 patients with craniosynostosis were studied. Classification was based on the suture(s) involved and the associated clinical features. In syndromic cases, genetic analyses, including mutational screening of the hotspot regions of the FGFR1, FGFR2, FGFR3, and TWIST1 genes, karyotyping and FISH study of TWIST1, were performed. The majority (88%) of all patients with craniosynostosis were nonsyndromic. The sagittal suture was most commonly involved, followed by the coronal, metopic, and lambdoid sutures. Male, twin gestation, and very low birth weight were risk factors for craniosynostosis. Syndromic craniosynostosis was detected in 24 patients. In 17 of these patients, Apert, Crouzon, Pfeiffer, Muenke, or Saethre-Chotzen syndromes were identified. In one patient, multiple-suture craniosynostosis was associated with achondroplasia. Clinical signs were not typical for any particular syndrome in six patients. Genetic abnormalities were detected in 18 syndromic patients and in 8 relatives. In addition to 10 different, known mutations in FGFR1,FGFR2 or FGFR3, one novel missense mutation, c.528C>G(p.Ser176Arg), was detected in the TWIST1 gene of a patient with Saethre-Chotzen syndrome. Our results indicate that detailed clinical assessment is of paramount importance in the classification of patients and allows indication of targeted molecular testing with the highest possible diagnostic yield. PMID:26289989

  8. Impact of genetic polymorphisms on clinical response to antithrombotics

    Directory of Open Access Journals (Sweden)

    Kena J Lanham

    2010-06-01

    Full Text Available Kena J Lanham1,2, Julie H Oestreich3, Steven P Dunn1,2, Steven R Steinhubl41Pharmacy Services, UK HealthCare, University of Kentucky, Lexington, Kentucky, USA; 2Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA; 3Department of Pharmacy Practice, College of Pharmacy, University of Nebraska, Omaha, Nebraska, USA; 4The Medicines Company, Zurich, Switzerland and The Geisinger Clinic, Danville, Pennsylvania, USAAbstract: Antithrombotic therapy, including anticoagulants as well as antiplatelet drugs, is an important component in the treatment of cardiovascular disease. Variability in response to such medications, of which pharmacogenetic response is a major source, can decrease or enhance the benefits expected. This review is a comprehensive assessment of the literature published to date on the effects of genetic polymorphisms on the actions of a variety of antithrombotic medications, including warfarin, clopidogrel, prasugrel, and aspirin. Literature evaluating surrogate markers in addition to the impact of pharmacogenetics on clinical outcomes has been reviewed. The results of the studies are conflicting as to what degree pharmacogenetics will affect medication management in cardiovascular disease. Additional research is necessary to discover, characterize, and prospectively evaluate genetic and non-genetic factors that impact antithrombotic treatment in order to maximize the effectiveness and limit the harmful effects of these valuable agents.Keywords: aspirin, warfarin, clopidogrel, prasugrel, pharmacogenetic, antithrombotic, antiplatelet

  9. Focus on PCSK9 Inhibitors: From Genetics to Clinical Practice.

    Science.gov (United States)

    Sabatine, Marc S; Underberg, James A; Koren, Michael; Baum, Seth J

    2016-10-01

    Elevation of low-density lipoprotein cholesterol (LDL-C) is an important cause of atherosclerotic cardiovascular disease (ASCVD). Over the years, clinical outcome studies with LDL-C lowering agents have revealed that reducing LCL-C levels is effective in reducing rates of major ASCVD events. Although secondary factors play a role in clinical expression, severe lipid disorders often have a strong genetic component. Genetic revelations have provided novel targets for improving LDL-C management in high-risk individuals. Most recently, researchers have explored how the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) alters LDL metabolism and lowers LDL-C levels to achieve lipid goals and potentially reduce ASCVD risk in patients with severe lipid disorders, including familial hypercholesterolemia (FH). This CMHC Spotlight article summarizes the clinical evidence demonstrating the safety, tolerability, and efficacy of PCSK9 inhibitors in lowering LDL-C levels. Reductions in LDL-C levels by PCSK9 inhibitors alone in patients who are statin intolerant or combined with maximally tolerated statins in patients with severe lipid disorders demonstrate the potential for reduced morbidity and mortality associated with ASCVD. PMID:27422124

  10. A clinical perspective on ethical issues in genetic testing.

    Science.gov (United States)

    Sijmons, R H; Van Langen, I M; Sijmons, J G

    2011-05-01

    Genetic testing is traditionally preceded by counselling to discuss its advantages and disadvantages with individuals so they can make informed decisions. The new technique of whole genome or exome sequencing, which is currently only used in research settings, can identify many gene mutations, including substantial numbers of mutations with unknown pathological effect; it may, therefore, threaten this balanced approach if it is used in a clinical setting. We discuss the ethical challenges of several approaches to pre- and postnatal DNA testing, individual privacy versus the interests of families and of scientists, and the clinician's duty to re-contact if new information or options become available. PMID:21574071

  11. Clinical, serological and genetic predictors of inflammatory bowel disease course

    Institute of Scientific and Technical Information of China (English)

    Laurent Beaugerie; Harry Sokol

    2012-01-01

    Patients with extensive or complicated Crohn's disease (CD) at diagnosis should be treated straightaway with immunosuppressive therapy according to the most recent guidelines.In patients with localized and uncomplicated CD at diagnosis,early use of immunosuppressive therapy is debated for preventing disease progression and limiting the disabling clinical impact.In this context,there is a need for predictors of benign or unfavourable subsequent clinical course,in order to avoid over-treating with risky drugs those patients who would have experienced spontaneous mid-term asymptomatic disease without progression towards irreversible intestinal lesions.At diagnosis,an age below 40 years,the presence of perianal lesions and the need for treating the first flare with steroids have been consistently associated with an unfavourable subsequent 5-year or 10-year clinical course.The positive predictive value of unfavourable course in patients with 2 or 3 predictors ranges between 0.75 and 0.95 in population-based and referral centre cohorts.Consequently,the use of these predictors can be integrated into the elements that influence individual decisions.In the CD postoperative context,keeping smoking and history of prior resection are the strongest predictors of disease symptomatic recurrence.However,these clinical predictors alone are not as reliable as severity of early postoperative endoscopic recurrence in clinical practice.In ulcerative colitis (UC),extensive colitis at diagnosis is associated with unfavourable clinical course in the first 5 to 10 years of the disease,and also with long-term colectomy and colorectal inflammation-associated colorectal cancer.In patients with extensive UC at diagnosis,a rapid step-up strategy aiming to achieve sustained deep remission should therefore be considered.At the moment,no reliable serological or genetic predictor of inflammatory bowel disease clinical course has been identified.

  12. Points to consider for prioritizing clinical genetic testing services

    DEFF Research Database (Denmark)

    Severin, Franziska; Borry, Pascal; Cornel, Martina C;

    2015-01-01

    testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit...... at the time of testing. Further discussion and better evidence is needed before clearly defined recommendations can be made or a prioritization algorithm proposed. To our knowledge, this is the first time a clinical society has initiated a decision process about health-care prioritization on a European level......, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management.European Journal of Human Genetics advance online publication, 24 September 2014; doi:10.1038/ejhg.2014.190....

  13. Genetic Architecture of clinical mastitis traits in dairy cattle

    DEFF Research Database (Denmark)

    Sahana, Goutam; Guldbrandtsen, Bernt; Lund, Mogens Sandø

    2012-01-01

    investigate the genetic architecture of clinical mastitis and somatic cell score traits in dairy cattle using a high density (HD) SNP panel. Mastitis, an inflammation of the mammary gland most commonly caused by bacterial infection, is a frequent disease in dairy cattle. Clinical mastitis and somatic cell...... score from first three lactations were studied for association with SNP markers in 4,200 progeny-tested Nordic Holstein bulls. Single trait breeding values were used as phenotypes. All the individuals were genotyped with BovineSNP50 Beadchip. Part of this population was also genotyped with the Bovine...... mixed model analysis. After Bonferroni correction 12, 372 SNP exhibited genome-wide significant associations with mastitis related traits. A total 61 QTL regions on 22 chromosomes associated with mastitis related traits were identified. The SNP with highest effect explained 5.6% of the variance of the...

  14. Translating colorectal cancer genetics into clinically useful biomarkers.

    Science.gov (United States)

    Morley-Bunker, A; Walker, L C; Currie, M J; Pearson, J; Eglinton, T

    2016-08-01

    Colorectal cancer (CRC) is a major health problem worldwide accounting for over a million deaths annually. While many patients with Stage II and III CRC can be cured with combinations of surgery, radiotherapy and chemotherapy, this is morbid costly treatment and a significant proportion will suffer recurrence and eventually die of CRC. Increased understanding of the molecular pathogenesis of CRC has the potential to identify high risk patients and target therapy more appropriately. Despite increased understanding of the molecular events underlying CRC development, established molecular techniques have only produced a limited number of biomarkers suitable for use in routine clinical practice to predict risk, prognosis and response to treatment. Recent rapid technological developments, however, have made genomic sequencing of CRC more economical and efficient, creating potential for the discovery of genetic biomarkers that have greater diagnostic, prognostic and therapeutic capabilities for the management of CRC. This paper reviews the current understanding of the molecular pathogenesis of CRC, and summarizes molecular biomarkers that surgeons will encounter in current clinical use as well as those under development in clinical and preclinical trials. New molecular technologies are reviewed together with their potential impact on the understanding of the molecular pathogenesis of CRC and their potential clinical utility in classification, diagnosis, prognosis and targeting of therapy. PMID:26990814

  15. Genetically engineered livestock for agriculture: a generation after the first transgenic animal research conference.

    Science.gov (United States)

    Murray, James D; Maga, Elizabeth A

    2016-06-01

    At the time of the first Transgenic Animal Research Conference, the lack of knowledge about promoter, enhancer and coding regions of genes of interest greatly hampered our efforts to create transgenes that would express appropriately in livestock. Additionally, we were limited to gene insertion by pronuclear microinjection. As predicted then, widespread genome sequencing efforts and technological advancements have profoundly altered what we can do. There have been many developments in technology to create transgenic animals since we first met at Granlibakken in 1997, including the advent of somatic cell nuclear transfer-based cloning and gene editing. We can now create new transgenes that will express when and where we want and can target precisely in the genome where we want to make a change or insert a transgene. With the large number of sequenced genomes, we have unprecedented access to sequence information including, control regions, coding regions, and known allelic variants. These technological developments have ushered in new and renewed enthusiasm for the production of transgenic animals among scientists and animal agriculturalists around the world, both for the production of more relevant biomedical research models as well as for agricultural applications. However, even though great advancements have been made in our ability to control gene expression and target genetic changes in our animals, there still are no genetically engineered animal products on the market for food. World-wide there has been a failure of the regulatory processes to effectively move forward. Estimates suggest the world will need to increase our current food production 70 % by 2050; that is we will have to produce the total amount of food each year that has been consumed by mankind over the past 500 years. The combination of transgenic animal technology and gene editing will become increasingly more important tools to help feed the world. However, to date the practical benefits of

  16. Highlights From the Third Annual Mayo Clinic Conference on Systems Engineering and Operations Research in Health Care

    OpenAIRE

    Kamath, Janine R. A.; Osborn, John B; Roger, Véronique L; Rohleder, Thomas R.

    2011-01-01

    In August 2010, the Third Annual Mayo Clinic Conference on Systems Engineering and Operations Research in Health Care was held. The continuing mission of the conference is to gather a multidisciplinary group of systems engineers, clinicians, administrators, and academic professors to discuss the translation of systems engineering methods to more effective health care delivery. Education, research, and practice were enhanced via a mix of formal presentations, tutorials, and informal gatherings...

  17. Statin-associated myopathy: from genetic predisposition to clinical management.

    Science.gov (United States)

    Vrablik, M; Zlatohlavek, L; Stulc, T; Adamkova, V; Prusikova, M; Schwarzova, L; Hubacek, J A; Ceska, R

    2014-01-01

    Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results. PMID:25428737

  18. Ullrich Congenital Muscular Dystrophy (UCMD: Clinical and Genetic Correlations

    Directory of Open Access Journals (Sweden)

    Bita BOZORGMEHR

    2013-08-01

    Full Text Available How to Cite This Article: Bozorgmehr B, Kariminejad A, Nafissi Sh, Jebelli B, Andoni U, Gartioux C, Ledeuil C, Allamand Y, Richard P, Kariminejad MH. Ullrich Congenital Muscular Dystrophy (UCMD:Clinical and Genetic Correlations. Iran J Child Neurol. 2013 Summer; 7(3: 15-22.  Objective:Ullrich congenital muscular dystrophy (UCMD corresponds to the severe end of the clinical spectrum of neuromuscular disorders caused by mutations in the genes encoding collagen VI (COL VI. We studied four unrelated families with six affected children that had typical UCMD with dominant and recessive inheritance.Materials & MethodsFour unrelated Iranian families with six affected children with typical UCMD were analyzed for COLVI secretion in skin fibroblast culture and the secretion of COLVI in skin fibroblast culture using quantitative RT–PCR (Q-RT-PCR, and mutation identification was performed by sequencing of complementary DNA.ResultsCOL VI secretion was altered in all studied fibroblast cultures. Two affected sibs carried a homozygous nonsense mutation in exon 12 of COL6A2, while another patient had a large heterozygous deletion in exon 5-8 of COL6A2. The two other affected sibs had homozygote mutation in exon 24 of COL6A2, and the last one was homozygote in COL6A1.ConclusionIn this study, we found out variability in clinical findings and genetic inheritance among UCMD patients, so that the patient with complete absence of COLVI was severely affected and had a large heterozygous deletion in COL6A2. In contrast, the patients with homozygous deletion had mild to moderate decrease in the secretion of COL VI and were mildly tomoderately affected.References1. Voit T. Congenital Muscular Dystrophies Brain Dev 1998;20(2: 65-74.2. Ullrich OZ Ges. Scleroatonic Muscular Dystrophy. NeurolPsychiatr 1930;126:171-201.3. Ullrich O. Monatsschr. Kinderheilkd 1930;47:502-10.4. Mercuri E, Yuva Y, Brown SC, Brockington M, Kinali M, Jungbluth H, et al. Collagen VI involvement in

  19. Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico

    Directory of Open Access Journals (Sweden)

    Hilda Montero

    2012-01-01

    Full Text Available Human rhinovirus (HRV is a leading cause of acute respiratory infection (ARI in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not as frequently as HRV-A, which was the most frequent species. Most of the cases of the three species of HRV were in children under 2 years of age, and all species were associated with very mild and moderate ARI.

  20. Update on clinical trials: genetic targets in breast cancer.

    Science.gov (United States)

    Lim, Bora; Cream, Leah V; Harvey, Harold A

    2013-01-01

    Breast cancer is the most commonly diagnosed cancer in women in United States. From data of American Cancer Society from 2007 reported total of 178,480 women diagnosed with breast cancer. The death rate from breast cancer has decreased in North America over time, but still accounts for second highest cancer death, following lung cancer. Breast cancer is staged based on tumor size, nodal involvement, and distant metastasis like any other solid tumors. However clinical staging is not the only important factor in management of breast cancer. Various molecular features divides breast cancer into many subgroups - that act differently, and respond differently from therapy. Thus the focus of breast cancer treatment has evolved focusing on specific targets. The most important biologic markers in subtyping of breast cancer so far are hormone receptor positivity and HER2/neu protein expression. Five molecular subtypes using intrinsic gene set include Basal mRNA, HER2 + mRNA, Luminal AmRNA, Luminal B mRNA, and Normal-like mRNA. In addition, better understanding of genetic target of breast cancer has given us arsenal of personalized, and more effective treatment approach.This review will focus on examples that highlight several mechanism of tumorigenesis, giving us not just understanding of gene pathways and the molecular biology, that could lead us to therapeutic target. Several important molecular targets have been investigated in preclinical and clinical trials, others are yet to be explored. We will also describe genetic mechanisms discovery related to overcoming resistance to current targeted therapies in breast cancer, including hormone receptor expression and HER 2- neu amplification. We will also review other exciting developments in understanding of breast cancer, the tumor microenvironment and cancer stem cells, and targeting agents in that area. PMID:23288634

  1. Medical genetics is playing an important role in the public health care in China Conference Report for The International Conference of Medical Genetics 2004, Beijing (ICMG 2004, Beijing)%医学遗传学在中国公共卫生事业中发挥重要作用--北京2004医学遗传学国际学术研讨会报告

    Institute of Scientific and Technical Information of China (English)

    Tian-Jian CHEN; Nanbert Zhong

    2005-01-01

    The International Conference of Medical Genetics 2004 (ICMG2004) was held at Peking University Health Science Center on July 14-18, 2004. This conference is a part of the series that have been organized by the North American Association of Chinese Medical Geneticists (NAACMG) and the Chinese Medical Genetics Association (CMGA) and was initialized by the year of 2000 at Nanjing (ICMG2000, Nanjing). The mission of the series is to promote research, education, and clinical practice on medical genetics in China as well as in south Asian countries. This year, more than 200 participants from Mainland China, Taiwan, Hong Kong, England, and United States attended the ICMG2004. The conference opened with a remark addressed by Dr. Qi-de Han, the Vice Chairman of the Standing Committee of National Congress, who is the Director of Peking University Health Science Center and the Executive President of Peking University. Dr. Owen Rennet, Scientific Director of NICHD, NIH, gave a keynote speech at the opening session. Six sessions, chaired by Drs. Virginia Anderson, Wai-Yee Chan, Tian-jian Chen, Jiang Gu, Jian Han, Tao-Sheng Huang, Marilyn Li, Gary Lu, Ming Qi, Bai-Lin Wu, Nanbert Zhong, Chun-Yan Zhou, have covered various aspects of medical genetics with focus on birth defect, which is different from the main focus of neurogenetic disorders at ICMG2000. These aspects include inborn error of metabolism, intervention of birth defects, prenatal diagnosis and newborn screening, chromosome abnormalities, molecular basis of genetic disorders, environmental factors and birth defects, and genetic counseling and clinical management.

  2. The challenge of implementing genetic tests with clinical utility while avoiding unsound applications.

    Science.gov (United States)

    Cornel, Martina C; van El, Carla G; Borry, Pascal

    2014-01-01

    Genetics and genomics have developed fast in the last decade, but have not revolutionized medicine, as some had expected. While translation of research findings to public health applications is lagging behind, direct-to-consumer (DTC) offers of genetic testing have become available, both for monogenic and severe genetic disorders and for genetic variants possibly associated with common complex diseases (susceptibility variants). The European Society of Human Genetics is concerned about the way in which commercial companies are currently introducing genetic tests into the market outside of the scope of the traditional health-care system. There is a sort of a paradox between the lagging implementation in health care of the few genetic tests with proven clinical utility, on the one hand, and the speedy DTC offer of tests, with or without clinical utility. To translate research findings into appropriate clinical applications, assessment of the clinical validity and utility is needed. Many of the parameters needed in assessment frameworks are not available yet. Clinically relevant associations between genetic variants and disease risks have been established, e.g., in oncogenetics and cardiogenetics, and can be used to reflect on the possibilities and obstacles in using the new genetics in public health. In the absence of sufficient information on clinical validity and clinical utility, introduction of genetic tests in common complex disorders is often premature. Priority should be given to settings where clinical utility is proven or likely, to gain additional information concerning diagnosis, prognosis, and disease management. Monitoring and evaluation are essential. PMID:23055102

  3. Observations from the Mayo Clinic National Conference on Medicine and the Media.

    Science.gov (United States)

    Lantz, Jane C; Lanier, William L

    2002-12-01

    In September 2002, the Mayo Clinic National Conference on Medicine and the Media convened to consider the accurate, timely, and responsible reporting of medical news to the public. The more than 500 participants included medical and health journalists, scientific journal editors, physicians and other health care professionals, industry representatives, government officials, institutional public information officers, public relations professionals, patients, and representatives of patient advocacy groups. The goal of the conference was to bring together all facets of the medical news dissemination process with the hope of identifying ways to serve the public more effectively. Several key observations emerged: Medical news reports may be confusing because the underlying scientific issues are unresolved and open to multiple interpretations. People who are ill have different information needs than the rest of the public. Journalists' primary concern is accurate, clear reporting, with secondary concern for a story's consequences. Journalists consider themselves primarily reporters rather than educators, but the public expects reporting to contain an educational element. Financial and other more subtle interests may influence the quality and content of scientific news releases, presentations in scientific journals, and stories covered by print and broadcast news media. Full disclosure of commercial support and affiliations, peer review of study reports, and formal guidelines for conduct may limit inappropriate financial influence. PMID:12479517

  4. Mild Lafora disease: clinical, neurophysiologic, and genetic findings.

    Science.gov (United States)

    Ferlazzo, Edoardo; Canafoglia, Laura; Michelucci, Roberto; Gambardella, Antonio; Gennaro, Elena; Pasini, Elena; Riguzzi, Patrizia; Plasmati, Rosaria; Volpi, Lilia; Labate, Angelo; Gasparini, Sara; Villani, Flavio; Casazza, Marina; Viri, Maurizio; Zara, Federico; Minassian, Berge A; Turnbull, Julie; Serratosa, Jose M; Guerrero-López, Rosa; Franceschetti, Silvana; Aguglia, Umberto

    2014-12-01

    We report clinical, neurophysiologic, and genetic features of an Italian series of patients with Lafora disease (LD) to identify distinguishing features of those with a slowly progressive course. Twenty-three patients with LD (17 female; 6 male) were recruited. Mean age (± SD) at the disease onset was 14.5 ± 3.9 years and mean follow-up duration was 13.2 ± 8.0 years. NHLRC1 mutations were detected in 18 patients; EPM2A mutations were identified in 5. Patients who maintained >10 years gait autonomy were labeled as "mild" and were compared with the remaining LD patients with a typical course. Six of 23 patients were mild and presented significantly delay in the age at onset, lower neurologic disability score at 4 years after the onset, less severe seizure phenotype, lower probability of showing both photoparoxysmal response on electroencephalography (EEG) and giant somatosensory evoked potentials, as compared to patients with typical LD. However, in both mild and typical LD patients, EEG showed disorganization of background activity and frequent epileptiform abnormalities. Mild LD patients had NHLRC1 mutations and five of six carried homozygous or compound heterozygous D146N mutation. This mutation was found in none of the patients with typical LD. The occurrence of specific NHLRC1 mutations in patients with mild LD should be taken into account in clinical practice for appropriate management and counseling. PMID:25270369

  5. Hamartomatous polyps - a clinical and molecular genetic study.

    Science.gov (United States)

    Jelsig, Anne Marie

    2016-08-01

    Hamartomatous polyps (HPs) in the gastrointestinal (GI) tract are rare compared to other types of GI polyps, yet they are the most common type of polyp in children. The symptoms are usually rectal bleeding, abdominal pain, obstipation, anaemia, and/or small bowel obstruction. The polyps are typically removed concurrently with endoscopy when located in the colon, rectum, or stomach, whereas polyps in the small bowel are removed during push-enteroscopy, device-assisted enteroscopy, or by surgery. HPs can be classified as juvenile polyps or Peutz-Jeghers polyps based on their histopathological appearance. Patients with one or a few juvenile polyps are usually not offered clinical follow-up as the polyp(s) are considered not to harbour any malignant potential. Nevertheless, it is important to note that juvenile polyps and HPs are also found in patients with hereditary hamartomatous polyposis syndromes (HPS). Patients with HPS have an increased risk of cancer, recurrences of polyps, and extraintestinal complications. The syndromes are important to diagnose, as patients should be offered surveillance from childhood or early adolescence. The syndromes include juvenile polyposis syndrome, Peutz-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing.   Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps in the colon and rectum in Denmark in 1995-2014. Based on the Danish Pathology Data Bank we found that 1772 patients had 2108 JPs examined in the period, and we

  6. Genetics of language disorders: Clinical conditions, phenotypes, and genes

    Czech Academy of Sciences Publication Activity Database

    Rice, M.; Smolík, Filip

    Oxford : Oxford University Press, 2007 - (Gaskell, G.), s. 685-700 ISBN 978-0-19-856897-1 Institutional research plan: CEZ:AV0Z70250504 Keywords : language genetics * language disorders * behavior genetics Subject RIV: AN - Psychology

  7. AmpC β-Lactamase in an Escherichia coli Clinical Isolate Confers Resistance to Expanded-Spectrum Cephalosporins

    OpenAIRE

    Mammeri, Hedi; Nazic, Hasan; Naas, Thierry; Poirel, Laurent; Léotard, Sophie; Nordmann, Patrice

    2004-01-01

    Cloning, sequencing, and biochemical analysis identified a novel AmpC-type β-lactamase conferring resistance to extended-spectrum cephalosporins in an Escherichia coli clinical isolate. This enzyme, exhibiting 14 amino acid substitutions compared to a reference AmpC cephalosporinase of E. coli, hydrolyzed ceftazidime and cefepime significantly.

  8. Genetic counselors: translating genomic science into clinical practice

    OpenAIRE

    Bennett, Robin L.; Hampel, Heather L.; Mandell, Jessica B.; Marks, Joan H.

    2003-01-01

    In a time of emerging genetic tests and technologies, genetic counselors are faced with the challenge of translating complex genomic data into information that will aid their client’s ability to learn about, understand, make, and cope with decisions relating to genetic diagnoses. The first of two companion articles in this issue examines the role of the genetic counselor, particularly in counseling individuals at risk for or diagnosed with breast cancer, in an era of high-tech health care and...

  9. Mitochondrial diseases: an overview of genetics, pathogenesis, clinical features and an approach to diagnosis and treatment.

    Directory of Open Access Journals (Sweden)

    Singhal N

    2000-07-01

    Full Text Available Defects in structures or functions of mitochondria, mainly involving the oxidative phosphorylation, mitochondrial biogenesis and other metabolic pathways have been shown to be associated with a wide spectrum of clinical phenotypes. The ubiquitous nature of mitochondria and their unique genetic features contribute to the clinical, biochemical and genetic heterogenecity of mitochondrial diseases. This article focuses on the recent advances in the field of mitochondrial disorders with respect to the consequences for an advanced clinical and genetic diagnostics. In addition, an overview on recently identified genetic defects and their pathogenic molecular mechanisms are given.

  10. Hereditary multiple exostoses: from genetics to clinical syndrome and complications

    Energy Technology Data Exchange (ETDEWEB)

    Vanhoenacker, Filip M.; Hul, Wim van; Wuyts, Wim; Willems, P.J.; Schepper, Arthur M. de

    2001-12-01

    Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses.

  11. Hereditary multiple exostoses: from genetics to clinical syndrome and complications

    International Nuclear Information System (INIS)

    Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses

  12. Clinical and genetic features of ataxia-telangiectasia

    International Nuclear Information System (INIS)

    There are several variants of ataxia-telangiectasia (A-T): classical A-T with marked radiation sensitivity; classical A-T with intermediate levels of radiation sensitivity; mild A-T with intermediate levels of radiation sensitivity; A-T without telangiectasia; A-T without oculomoto apraxia; and A-T with microcephaly. These disorders are probably caused by different allelic mutations, because affected sibs resemble the index patients, and because there is an association of certain haplo-types of 11q22-23 with specific phenotypes. The Nijmegen Breakage Syndrome, with its lack of ataxia, seems on clinical grounds to be a different disorder. Although A-T is almost always inherited as an autosomal recessive, there are some unusual features; an unexpectedly low parental consanguinity rate, an incidence in sibs that is < 0.25, and occurrence of disease in many different races and in the offspring of mixed race unions. Moreover, looking at haplotypes from 63 UK patients, there is a remarkably low incidence of homozygosity. An autosomal recessive condition that is deficient in parental consanguinity, and in homozygosity for the region around the gene, can be explained by J.H. Edwards' hypothesis that homozygosity for alleles at a neighbouring locus are lethal early in embryogenesis. Other possible mechanisms to explain the unusual genetic features are discussed. (author)

  13. LMNA cardiomyopathy: cell biology and genetics meet clinical medicine

    Directory of Open Access Journals (Sweden)

    Jonathan T. Lu

    2011-09-01

    Full Text Available Mutations in the LMNA gene, which encodes A-type nuclear lamins (intermediate filament proteins expressed in most differentiated somatic cells, cause a diverse range of diseases, called laminopathies, that selectively affect different tissues and organ systems. The most prevalent laminopathy is cardiomyopathy with or without different types of skeletal muscular dystrophy. LMNA cardiomyopathy has an aggressive clinical course with higher rates of deadly arrhythmias and heart failure than most other heart diseases. As awareness among physicians increases, and advances in DNA sequencing methods make the genetic diagnosis of LMNA cardiomyopathy more common, cardiologists are being faced with difficult questions regarding patient management. These questions concern the optimal use of intracardiac cardioverter defibrillators to prevent sudden death from arrhythmias, and medical interventions to prevent heart damage and ameliorate heart failure symptoms. Data from a mouse model of LMNA cardiomyopathy suggest that inhibitors of mitogen-activated protein kinase (MAPK signaling pathways are beneficial in preventing and treating cardiac dysfunction; this basic research discovery needs to be translated to human patients.

  14. Clinical and genetic features of ataxia-telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Bundey, S. [Birmingham Maternity Hospital (United Kingdom). Clinical Genetics Unit

    1994-12-01

    There are several variants of ataxia-telangiectasia (A-T): classical A-T with marked radiation sensitivity; classical A-T with intermediate levels of radiation sensitivity; mild A-T with intermediate levels of radiation sensitivity; A-T without telangiectasia; A-T without oculomoto apraxia; and A-T with microcephaly. These disorders are probably caused by different allelic mutations, because affected sibs resemble the index patients, and because there is an association of certain haplo-types of 11q22-23 with specific phenotypes. The Nijmegen Breakage Syndrome, with its lack of ataxia, seems on clinical grounds to be a different disorder. Although A-T is almost always inherited as an autosomal recessive, there are some unusual features; an unexpectedly low parental consanguinity rate, an incidence in sibs that is < 0.25, and occurrence of disease in many different races and in the offspring of mixed race unions. Moreover, looking at haplotypes from 63 UK patients, there is a remarkably low incidence of homozygosity. An autosomal recessive condition that is deficient in parental consanguinity, and in homozygosity for the region around the gene, can be explained by J.H. Edwards` hypothesis that homozygosity for alleles at a neighbouring locus are lethal early in embryogenesis. Other possible mechanisms to explain the unusual genetic features are discussed. (author).

  15. Clinical genetic testing for familial melanoma in Italy: a cooperative study

    OpenAIRE

    W.Bruno, P.Ghiorzo, L.Battistuzzi, P.A.Ascierto, M.Barile, S.Gargiulo, F.Gensini, S.Gliori, M.Guida, M.Lombardo, S.Manoukian, C.Menin, S.Nasti, P.Origone, B.Pasini,L. Pastorino, B.Peissel, M.A.Pizzichetta, P.Queirolo, M.Rodolfo, A.Romanini, M.C.Scaini, A.Testori, M.G.Tibiletti, D.Turchetti, S.A.Leachman, G.Bianchi Scarrà; IMI, Italian Melanoma Intergroup

    2009-01-01

    Background: The Italian Society of Human Genetics’ (SIGU) recommendations on genetic counseling and testing for hereditary melanoma state that clinical genetic testing can be offered to Italian melanoma families with at least two affected members. Objective: In the framework of a cooperative study, we sought to establish the frequency of cyclindependent kinase inhibitor 2A mutations in melanoma families that underwent clinical genetic counseling and testing in accordance with t...

  16. Clinical and Pharmacogenomic Implications of Genetic Variation in a Southern Ethiopian Population

    OpenAIRE

    Tekola-Ayele, Fasil; Adeyemo, Adebowale; Aseffa, Abraham; Hailu, Elena; Finan, Chris; Davey, Gail; Rotimi, Charles N.; Newport, Melanie J.

    2014-01-01

    Africa is home to genetically diverse human populations. We compared the genetic structure of the Wolaita ethnic population from southern Ethiopia (WETH, n=120) with HapMap populations using genome-wide variants. We investigated allele frequencies of 443 clinically and pharmacogenomically relevant genetic variants in WETH compared to HapMap populations. We found that WETH were genetically most similar to the Kenya Maasai and least similar to the Japanese in HapMap. Variant alleles associated ...

  17. Clinical Considerations of Preimplantation Genetic Diagnosis for Monogenic Diseases.

    Directory of Open Access Journals (Sweden)

    Xiaokun Hu

    Full Text Available The aim of this study was to explore factors contribute to the success of PGD cycles for monogenic diseases.During a 3-year period (January 2009 to December 2012, 184 consecutive ICSI-PGD cycles for monogenic diseases reaching the ovum pick-up and fresh embryo-transfer stage performed at the Reproductive Medicine Center of The First Affiliated Hospital Of Sun Yat-sen University were evaluated.ICSI was performed on 2206 metaphase II oocytes, and normal fertilization and cleavage rates were 83.4% (1840/2206 and 96.2% (1770/1840, respectively. In the present study, 60.5% (181/299 of day 3 good-quality embryos developed into good-quality embryos on day 4 after biopsy. Collectively, 42.9% clinical pregnancy rate (79/184 and 28.5% implantation rate (111/389 were presented. In the adjusted linear regression model, the only two significant factors affecting the number of genetically unaffected embryos were the number of biopsied embryos (coefficient: 0.390, 95%CI 0.317-0.463, P = 0.000 and basal FSH level (coefficient: 0.198, 95%CI 0.031-0.365, P = 0.021. In the adjusted binary logistic regression model, the only two significant factors affecting pregnancy outcome were the number of genetically available transferable embryos after PGD (adjusted OR 1.345, 95% CI 1.148-1.575, P = 0.000 and number of oocyte retrieved (adjusted OR 0.934, 95% CI 0.877-0.994, P = 0.031.There should be at least four biopsied embryos to obtain at least one unaffected embryos in a PGD system for patients with single gene disorder and under the condition of basal FSH level smaller than 8.0mmol/L. Moreover, if only a low number (< 4 of biopsied embryos are available on day 3, the chance of unaffected embryos for transfer was small, with poor outcome.

  18. Genetics of schizophrenia: from animal models to clinical studies

    OpenAIRE

    Joober, Ridha; Boksa, Patricia; Benkelfat, Chawki; Rouleau, Guy

    2002-01-01

    Genetic epidemiological studies strongly suggest that additive and interactive genes, each with small effects, mediate the genetic vulnerability for schizophrenia. With the human genome working draft at hand, candidate gene (and ultimately large-scale genome-wide) association studies are gaining renewed interest in the effort to unravel the complex genetics of schizophrenia. In the absence of an unequivocally established biological theory for schizophrenia, identifying candidate genes to be t...

  19. The next controversy in genetic testing: clinical data as trade secrets?

    OpenAIRE

    Cook-Deegan, Robert; Conley, John M.; Evans, James P.; Vorhaus, Daniel

    2012-01-01

    Sole-source business models for genetic testing can create private databases containing information vital to interpreting the clinical significance of human genetic variations. But incomplete access to those databases threatens to impede the clinical interpretation of genomic medicine. National health systems and insurers, regulators, researchers, providers and patients all have a strong interest in ensuring broad access to information about the clinical significance of variants discovered th...

  20. Head and neck paragangliomas: clinical and molecular genetic classification.

    Science.gov (United States)

    Offergeld, Christian; Brase, Christoph; Yaremchuk, Svetlana; Mader, Irina; Rischke, Hans Christian; Gläsker, Sven; Schmid, Kurt W; Wiech, Thorsten; Preuss, Simon F; Suárez, Carlos; Kopeć, Tomasz; Patocs, Attila; Wohllk, Nelson; Malekpour, Mahdi; Boedeker, Carsten C; Neumann, Hartmut P H

    2012-01-01

    Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies. PMID:22584701

  1. Head and neck paragangliomas: clinical and molecular genetic classification

    Directory of Open Access Journals (Sweden)

    Christian Offergeld

    2012-01-01

    Full Text Available Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5, and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

  2. Do nuclear-encoded core subunits of mitochondrial complex I confer genetic susceptibility to schizophrenia in Han Chinese populations?

    Science.gov (United States)

    Li, Xiao; Zhang, Wen; Tang, Jinsong; Tan, Liwen; Luo, Xiong-jian; Chen, Xiaogang; Yao, Yong-Gang

    2015-01-01

    Schizophrenia is one of the most prevalent psychiatric disorders with complex genetic etiology. Accumulating evidence suggests that energy metabolism and oxidative stress play important roles in the pathophysiology of schizophrenia. Dysfunction of mitochondrial respiratory chain and altered expression of complex I subunits were frequently reported in schizophrenia. To investigate whether nuclear-encoded core subunit genes of mitochondrial complex I are associated with schizophrenia, we performed a genetic association study in Han Chinese. In total, 46 tag single nucleotide polymorphisms (SNPs) from 7 nuclear-encoded core genes of mitochondrial complex I were genotyped in 918 schizophrenia patients and 1042 healthy controls. We also analyzed these SNPs in a large sample mainly composed of Europeans through using the available GWAS datasets from the Psychiatric Genomics Consortium (PGC). No significant associations were detected between these SNPs and schizophrenia in Han Chinese and the PGC data set. However, we observed nominal significant associations of 2 SNPs in the NDUFS1 gene and 4 SNPs in the NDUFS2 gene with early onset schizophrenia (EOS), but none of these associations survived the Bonferroni correction. Taken together, our results suggested that common SNPs in the nuclear-encoded core subunit genes of mitochondrial complex I may not confer genetic susceptibility to schizophrenia. PMID:26053550

  3. Genetic Polymorphisms in the Fat Mass and Obesity-Associated Gene Confers Risk of Obesity in Iraqi Population

    Directory of Open Access Journals (Sweden)

    Shatha Ramadhanzaidan

    2011-01-01

    Full Text Available Problem statement: Obesity is strongly influenced by genetic factors, with an estimated heritability of 60% BMI. Genetic susceptibility to the common form of obesity appears to be polygenic. Although theoretical analyses emphasized the power of genetic association study in common polygenic diseases, the search for genes conferring the risk of obesity has thus far not been very successful. Approach: In this research, DNA was extracted from 100 individuals who diagnosed as diabetes mellitus and have obesity referred to Al-Kindy research and therapeutic unit and in Baghdad 40 subject used as control. Thirty cycles of PCR were performed on exons 2 and 3 of the FSHâ gene, which encode for the translated FSH â protein. Results: For each exon, 30 cycles of PCR were performed at 95°C for 1 min, 55°C for 30sec and 72°C for 30 sec. Samples were subjected to sequencing and the results showed that the signals were poor and there is no capability to analyze so, we were recommended to do cloning the fragment of DNA to gain good signals. We did not observe significant association between rs9939609 and type 2 diabetes. Conclusion: Two SNPs (rs16952777 and rs1107355 in LD block 1 were nominally associated with type 2 diabetes. SNPs in the same block were also nominally associated with fasting glucose concentrations in no diabetic subjects (control subject. However, none of these associations remained significant after adjustment for multiple testing.

  4. Citing conduct, individualizing symptoms: Accomplishing autism diagnosis in clinical case conferences.

    Science.gov (United States)

    Turowetz, Jason

    2015-10-01

    In this paper, I examine how clinicians at a clinic for developmental disabilities in the United States determine whether children being evaluated for autism spectrum disorder (ASD) showed symptoms of that condition. Drawing on a convenience sample of 61 audio and video recorded case conferences from two time periods (1985 and 2011-15), and combining Conversation Analysis with insights from Actor Network Theory, I find that clinicians describe (via a representational practice called "citation") children's conduct in ways that advance diagnostic claims. More specifically, they portray key actants in the assessment process in patterned ways: the test instrument is represented as a neutral tool of measurement, the clinician as administrator and instructor; and the child as the focal figure whose conduct is made to appear independent of the other participants and suggestive of diagnostic symptoms. These tacit representational conventions conform to and reproduce the assumptions of standardized testing, according to which clinicians and tests are to be neutral arbiters of the child's abilities, and thereby provide for objective, warrantable findings. At the same time, however, by designing representations around the child's symptomatic conduct in this way, clinicians may minimize or elide their own contributions, and those of the test instrument, to the child's performance, and thereby make the child alone appear responsible for what are, in fact, interactionally-occasioned behaviors. PMID:26318210

  5. The mecA homolog mecC confers resistance against β-lactams in Staphylococcus aureus irrespective of the genetic strain background.

    Science.gov (United States)

    Ballhausen, Britta; Kriegeskorte, André; Schleimer, Nina; Peters, Georg; Becker, Karsten

    2014-07-01

    In staphylococci, methicillin resistance is mediated by mecA-encoded penicillin-binding protein 2a (PBP2a), which has a low affinity for beta-lactams. Recently, a novel PBP2a homolog was described as being encoded by mecC, which shares only 70% similarity to mecA. To prove that mecC is the genetic determinant that confers methicillin resistance in Staphylococcus aureus, a mecC knockout strain was generated. The S. aureus ΔmecC strain showed considerably reduced oxacillin and cefoxitin MICs (0.25 and 4 μg/ml, respectively) compared to those of the corresponding wild-type methicillin-resistant S. aureus (MRSA) strain (8 and 16 μg/ml, respectively). Complementing the mutant in trans with wild-type mecC restored the resistance to oxacillin and cefoxitin. By expressing mecC and mecA in different S. aureus clonal lineages, we found that mecC mediates resistance irrespective of the genetic strain background, yielding oxacillin and cefoxitin MIC values comparable to those with mecA. In addition, we showed that mecC expression is inducible by oxacillin, which supports the assumption that a functional beta-lactam-dependent regulatory system is active in MRSA strains possessing staphylococcal cassette chromosome mec (SCCmec) type XI. In summary, we showed that mecC is inducible by oxacillin and mediates beta-lactam resistance in SCCmec type XI-carrying strains as well as in different S. aureus genetic backgrounds. Furthermore, our results could explain the comparatively low MICs for clinical mecC-harboring S. aureus isolates. PMID:24752255

  6. International conference on clinical PET and molecular nuclear medicine (IPET 2007). Book of abstracts

    International Nuclear Information System (INIS)

    The International Atomic Energy Agency is organizing its first international conference on 'Clinical PET and Molecular Nuclear Medicine'. Medical imaging technologies have undergone explosive growth over the past two decades. Today, imaging is at a crossroad, with molecular targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Observing molecular interactions in the living body by the radiotracer technique has become known as 'molecular nuclear medicine'. Molecular nuclear medicine techniques analyze cellular biochemistry and its relationship to disease processes expressed in tissue and organ dysfunction, for diagnostic and therapeutic purposes. People can often have similar manifestations of disease, but no two patients will be the same. Functional radionuclide imaging and positron emission tomography (PET) provide excellent opportunities to follow the pathology in individual patients and therefore provide a means for tailored clinical management. These also provide the means to assess the response to treatment in a safe and non-invasive manner. Changes at molecular and cellular levels provide vital clues for evaluating the effectiveness of chosen clinical treatment plans. This information is expected to have a major impact on understanding disease, disease detection, individualised treatment, and drug development. Recently, considerable attention has been drawn to nuclear medicine with the visualization of biochemical processes in vivo such as PET studies with 18F-FDG in many different organs and in cancerous tissues. With the arrival of PET/CT systems there is a new era of accurate mapping of disease processes. Today, 18F-FDG is the most useful PET tracer for the detection, staging, treatment planning and management of cancer. There is mounting evidence for its competitive advantage over conventional techniques in major medical areas including oncology, cardiology, and neurology. Nuclear medicine is

  7. Assessment of Genetics Knowledge and Skills in Medical Students: Insight for a Clinical Neurogenetics Curriculum

    Science.gov (United States)

    Pearl, Phillip L.; Pettiford, Jennifer M.; Combs, Susan E.; Heffron, Ari; Healton, Sean; Hovaguimian, Alexandra; Macri, Charles J.

    2011-01-01

    The pace of discovery in biochemistry and genetics and its effect on clinical medicine places new curricular challenges in medical school education. We sought to evaluate students' understanding of neurogenetics and its clinical applications to design a pilot curriculum into the clinical neurology clerkship. We utilized a needs assessment and a…

  8. Genetics of Parkinson’s Disease - A Clinical Perspective

    Directory of Open Access Journals (Sweden)

    Sang-Myung Cheon

    2012-10-01

    Full Text Available Discovering genes following Medelian inheritance, such as autosomal dominant-synuclein and leucine-rich repeat kinase 2 gene, or autosomal recessive Parkin, P-TEN-induced putative kinase 1 gene and Daisuke-Junko 1 gene, has provided great insights into the pathogenesis of Parkinson’s disease (PD. Genes found to be associated with PD through investigating genetic polymorphisms or via the whole genome association studies suggest that such genes could also contribute to an increased risk of PD in the general population. Some environmental factors have been found to be associated with genetic factors in at-risk patients, further implicating the role of gene-environment interactions in sporadic PD. There may be confusion for clinicians facing rapid progresses of genetic understanding in PD. After a brief review of PD genetics, we will discuss the insight of new genetic discoveries to clinicians, the implications of ethnic differences in PD genetics and the role of genetic testing for general clinicians managing PD patients.

  9. 8th Argentinean Bioengineering Society Conference (SABI 2011) and 7th Clinical Engineering Meeting

    Science.gov (United States)

    Meschino, Gustavo Javier; Ballarin, Virginia L.

    2011-12-01

    In September 2011, the Eighteenth Edition of the Argentinean Bioengineering Society Conference (SABI 2011) and Seventh Clinical Engineering Meeting were held in Mar del Plata, Argetina. The Mar del Plata SABI Regional and the School of Engineering of the Universidad Nacional de Mar del Plata invited All bioengineers, engineers, physicists, mathematicians, biologists, physicians and health professionals working in the field of Bioengineering to participate in this event. The overall objectives of the Conference were: To provide discussion of scientific research results in Bioengineering and Clinical Engineering. To promote technological development experiences. To strengthen the institutional and scientific communication links in the area of Bioengineering, mainly between Universities of Latin America. To encourage students, teachers, researchers and professionals to establish exchanges of experiences and knowledge. To provide biomedical engineering technology solutions to the society and contributing ideas for low cost care. Conference photograph Conference photograph Conference photograph Conference photograph EXECUTIVE COMMITTEE SABI 2011 Chair Dra Virginia L Ballarin Universidad Nacional de Mar del Plata Co-Chair Dra Teresita R Cuadrado Universidad Nacional de Mar del Plata - CONICET Local Comittee Dr Gustavo Abraham Universidad Nacional de Mar del Plata - CONICET Dra Josefina Ballarre Universidad Nacional de Mar del Plata - CONICET Dr Eduardo Blotta Universidad Nacional de Mar del Plata Dra Agustina Bouchet Universidad Nacional de Mar del Plata Dr Marcel Brun Universidad Nacional de Mar del Plata Dra Silvia Ceré Universidad Nacional de Mar del Plata - CONICET Dra Mariela Azul Gonzalez Universidad Nacional de Mar del Plata - CONICET Dra Lucia Isabel Passoni Universidad Nacional de Mar del Plata Dr Juan Ignacio Pastore Universidad Nacional de Mar del Plata - CONICET Dra Adriana Scandurra Universidad Nacional de Mar del Plata SCIENTIFIC ADVISORY COMMITTEE

  10. Alpha1-antitrypsin deficiency: a clinical-genetic overview

    Directory of Open Access Journals (Sweden)

    Abboud RT

    2011-03-01

    in patients with chronic irreversible airflow obstruction, especially in those with early onset of disease or positive family history. Testing is also recommended for immediate family members of those with AATD, asthmatics with persistent airflow obstruction, and infants and older subjects with unexplained liver disease. There are over 100 different AAT gene variants; most are rare and only some are associated with clinical disease.Keywords: AAT, AATD, ZZ, early onset emphysema, panacinar emphysema, neonatal jaundice and hepatitis, childhood liver disease, genetics of alpha1-antitrypsin, alpha1-antitrypsin laboratory testing and phenotyping

  11. Twenty-Seventh Fungal Genetics Conference, Asilomar, CA, March 12-17, 2013

    Energy Technology Data Exchange (ETDEWEB)

    Walton, Jonathan

    2013-03-17

    This meeting brings together ~900 international scientists to discuss the latest research on fungal genetics. Sessions of particular relevance to DOE include lignocellulose degradation, cellulose conversion to fermentable sugars, fermentation of sugars to fuel molecules. Other sessions cover fungal diseases of biomass crops (miscanthus, corn, switchgrass, etc.).

  12. Genetic diversity confers colony-level benefits due to individual immunity.

    Science.gov (United States)

    Simone-Finstrom, Michael; Walz, Megan; Tarpy, David R

    2016-03-01

    Several costs and benefits arise as a consequence of eusociality and group-living. With increasing group size, spread of disease among nest-mates poses selective pressure on both individual immunity and group-level mechanisms of disease resistance (social immunity). Another factor known to influence colony-level expression of disease is intracolony genetic diversity, which in honeybees (Apis mellifera) is a direct function of the number of mates of the queen. Colonies headed by queens with higher mating numbers have less variable infections of decreased intensity, though the underlying mechanisms remain unclear. By pathogen-challenging larvae in vitro, we decoupled larval immune response from mechanisms of social immunity. Our results show that baseline immunity and degree of immune response do not vary with genetic diversity. However, intracolony variance in antimicrobial peptide production after pathogen challenge decreases with increasing genetic diversity. This reduction in variability of the larval immune response could drive the mitigation of disease observed in genetically diverse colonies. PMID:26961896

  13. Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

    DEFF Research Database (Denmark)

    Lundin, Catarina; Forestier, Erik; Klarskov Andersen, Mette;

    2014-01-01

    BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. METHODS...

  14. Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype

    OpenAIRE

    Kano, Hiroki; Kurahashi, Hiroki; Toda, Tatsushi

    2007-01-01

    Dactylaplasia, characterized by missing central digital rays, is an inherited mouse limb malformation that depends on two genetic loci. The first locus, Dac, is an insertional mutation around the dactylin gene that is inherited as a semidominant trait. The second locus is an unlinked modifier, mdac/Mdac, that is polymorphic among inbred strains. Mdac dominantly suppresses the dactylaplasia phenotype in mice carrying Dac. However, little is known about either locus or the nature of their inter...

  15. Molecular genetics of pancreatic carcinogenesis and their clinical significance

    NARCIS (Netherlands)

    Ottenhof, N.A.

    2012-01-01

    Like all types of cancer, pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is a disease of the genes and the genetic alterations that are involved in the development of PDAC have been under investigation for many years. The research described in this thesis focuses on

  16. Genetic mapping of two genes conferring resistance to powdery mildew in common bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Pérez-Vega, Elena; Trabanco, Noemí; Campa, Ana; Ferreira, Juan José

    2013-06-01

    Powdery mildew (PM) is a serious disease in many legume species, including the common bean (Phaseolus vulgaris L.). This study investigated the genetic control behind resistance reaction to PM in the bean genotype, Cornell 49242. The results revealed evidence supporting a qualitative mode of inheritance for resistance and the involvement of two independent genes in the resistance reaction. The location of these resistance genes was investigated in a linkage genetic map developed for the XC RIL population. Contingency tests revealed significant associations for 28 loci out of a total of 329 mapped loci. Fifteen were isolated or formed groups with less than two loci. The thirteen remaining loci were located at three regions in linkage groups Pv04, Pv09, and Pv11. The involvement of Pv09 was discarded due to the observed segregation in the subpopulation obtained from the Xana genotype for the loci located in this region. In contrast, the two subpopulations obtained from the Xana genotype for the BM161 locus, linked to the Co-3/9 anthracnose resistance gene (Pv04), and from the Xana genotype for the SCAReoli locus, linked to the Co-2 anthracnose resistance gene (Pv11), exhibited monogenic segregations, suggesting that both regions were involved in the genetic control of resistance. A genetic dissection was carried out to verify the involvement of both regions in the reaction to PM. Two resistant recombinant lines were selected, according to their genotypes, for the block of loci included in the Co-2 and Co-3/9 regions, and they were crossed with the susceptible parent, Xana. Linkage analysis in the respective F2 populations supported the hypothesis that a dominant gene (Pm1) was located in the linkage group Pv11 and another gene (Pm2) was located in the linkage group Pv04. This is the first report showing the localization of resistance genes against powdery mildew in Phaseolus vulgaris and the results offer the opportunity to increase the efficiency of breeding

  17. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Kristen N Stevens

    Full Text Available Congenital heart disease (CHD is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1 is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.

  18. Form Follows Function: A Model for Clinical Supervision of Genetic Counseling Students.

    Science.gov (United States)

    Wherley, Colleen; Veach, Patricia McCarthy; Martyr, Meredith A; LeRoy, Bonnie S

    2015-10-01

    Supervision plays a vital role in genetic counselor training, yet models describing genetic counseling supervision processes and outcomes are lacking. This paper describes a proposed supervision model intended to provide a framework to promote comprehensive and consistent clinical supervision training for genetic counseling students. Based on the principle "form follows function," the model reflects and reinforces McCarthy Veach et al.'s empirically derived model of genetic counseling practice - the "Reciprocal Engagement Model" (REM). The REM consists of mutually interactive educational, relational, and psychosocial components. The Reciprocal Engagement Model of Supervision (REM-S) has similar components and corresponding tenets, goals, and outcomes. The 5 REM-S tenets are: Learning and applying genetic information are key; Relationship is integral to genetic counseling supervision; Student autonomy must be supported; Students are capable; and Student emotions matter. The REM-S outcomes are: Student understands and applies information to independently provide effective services, develop professionally, and engage in self-reflective practice. The 16 REM-S goals are informed by the REM of genetic counseling practice and supported by prior literature. A review of models in medicine and psychology confirms the REM-S contains supervision elements common in healthcare fields, while remaining unique to genetic counseling. The REM-S shows promise for enhancing genetic counselor supervision training and practice and for promoting research on clinical supervision. The REM-S is presented in detail along with specific examples and training and research suggestions. PMID:25956951

  19. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans

    NARCIS (Netherlands)

    Verloop, H.; Dekkers, O.M.; Peeters, R.P.; Schoones, J.W.; Smit, J.W.

    2014-01-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clini

  20. Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E

    DEFF Research Database (Denmark)

    Semplicini, Claudio; Vissing, John; Dahlqvist, Julia R;

    2015-01-01

    OBJECTIVE: To determine the clinical spectrum of limb-girdle muscular dystrophy 2E (LGMD2E) and to investigate whether genetic or biochemical features can predict the phenotype of the disease. METHODS: All LGMD2E patients followed in participating centers were included. A specific clinical protocol...

  1. Adult-onset cerebellar Ataxia: a clinical and genetic Survey

    NARCIS (Netherlands)

    E. Brusse (Esther)

    2011-01-01

    textabstractCerebellar ataxias represent a heterogeneous group of neurodegenerative disorders. Two main categories are distinguished: hereditary and sporadic ataxias. Sporadic ataxias may be symptomatic or idiopathic. The clinical classification of hereditary ataxias is nowadays being replaced by an

  2. Familial renal cell carcinoma: clinical and molecular genetic aspects

    OpenAIRE

    Maher, E. R.; Yates, J. R. W.

    1991-01-01

    Renal cell carcinoma (RCC) accounts for 2% of all human cancer, but familial cases are infrequent. Riches (1963) and Griffin et al. (1984) in a population-based case-control study found a family history of renal cell carcinoma in 2.4% of affected patients compared to 1.4% of controls. Nevertheless the importance of inherited tumours in clinical practice and medical research is disproportionate to their frequency. In clinical practice recognition of familial RCC can provide opportunities to pr...

  3. COMT genetic variation confers risk for psychotic and affective disorders: a case control study

    Directory of Open Access Journals (Sweden)

    Lencz Todd

    2005-10-01

    Full Text Available Abstract Background Variation in the COMT gene has been implicated in a number of psychiatric disorders, including psychotic, affective and anxiety disorders. The majority of these studies have focused on the functional Val108/158Met polymorphism and yielded conflicting results, with limited studies examining the relationship between other polymorphisms, or haplotypes, and psychiatric illness. We hypothesized that COMT variation may confer a general risk for psychiatric disorders and have genotyped four COMT variants (Val158Met, rs737865, rs165599, and a SNP in the P2 promoter [-278A/G; rs2097603] in 394 Caucasian cases and 467 controls. Cases included patients with schizophrenia (n = 196, schizoaffective disorder (n = 62, bipolar disorder (n = 82, major depression (n = 30, and patients diagnosed with either psychotic disorder NOS or depressive disorder NOS (n = 24. Results SNP rs2097603, the Val/Met variant and SNP rs165599 were significantly associated (p = 0.004; p = 0.05; p = 0.035 with a broad "all affected" diagnosis. Haplotype analysis revealed a potentially protective G-A-A-A haplotype haplotype (-278A/G; rs737865; Val108/158Met; rs165599, which was significantly underrepresented in this group (p = 0.0033 and contained the opposite alleles of the risk haplotype previously described by Shifman et al. Analysis of diagnostic subgroups within the "all affecteds group" showed an association of COMT in patients with psychotic disorders as well as in cases with affective illness although the associated variants differed. The protective haplotype remained significantly underrepresented in most of these subgroups. Conclusion Our results support the view that COMT variation provides a weak general predisposition to neuropsychiatric disease including psychotic and affective disorders.

  4. DataGenno: building a new tool to bridge molecular and clinical genetics

    Directory of Open Access Journals (Sweden)

    Fabricio F Costa

    2011-03-01

    Full Text Available Fabricio F Costa1,2, Luciano S Foly1, Marcelo P Coutinho11DataGenno Interactive Research Ltd., Itaperuna, Rio de Janeiro, Brazil; 2Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University's Feinberg School of Medicine, Chicago, IL, USAAbstract: Clinical genetics is one of the most challenging fields in medicine, with thousands of children born every year with congenital defects that have no satisfactory diagnosis. There are more than 6,000 known single-gene disorders that can cause birth defects or diseases in approximately 1 in every 200 births. Clinical and molecular information on genetic diseases and syndromes are widespread in the literature, and there are few databases combining this information. Therefore, it is very challenging for health care professionals and researchers to translate the latest advances in science and medicine into effective clinical interventions and new treatments. In order to overcome this obstacle and promote networking, we are building DataGenno, an online medical and scientific portal. DataGenno has been developed to be a source of information on genetic diseases and syndromes for the needs of all heath care professionals and researchers. Our database will be able to integrate both clinical and molecular aspects of genetic diseases in a fully interactive environment. DataGenno’s system already contains clinical and molecular information for 300 diseases, with approximately 6,000 signs and symptoms of these diseases in a database combined with a search engine. Our main goal is to cover all genetic diseases described to date, providing not only clinical information such as morphological and anatomical features but also the most comprehensive molecular genetics/genomics features and available testing information. We are also developing ways to connect DataGenno’s portal with Electronic Health Records in order to improve the efficiency of patient care. Additionally

  5. Genetic Stratification in Myeloid Diseases: From Risk Assessment to Clinical Decision Support Tool

    Directory of Open Access Journals (Sweden)

    Yishai Ofran

    2014-10-01

    Full Text Available Genetic aberrations have become a dominant factor in the stratification of myeloid malignancies. Cytogenetic and a few mutation studies are the backbone of risk assessment models of myeloid malignancies which are a major consideration in clinical decisions, especially patient assignment for allogeneic stem cell transplantation. Progress in our understanding of the genetic basis of the pathogenesis of myeloid malignancies and the growing capabilities of mass sequencing may add new roles for the clinical usage of genetic data. A few recently identified mutations recognized to be associated with specific diseases or clinical scenarios may soon become part of the diagnostic criteria of such conditions. Mutational studies may also advance our capabilities for a more efficient patient selection process, assigning the most effective therapy at the best timing for each patient. The clinical utility of genetic data is anticipated to advance further with the adoption of deep sequencing and next-generation sequencing techniques. We herein suggest some future potential applications of sequential genetic data to identify pending deteriorations at time points which are the best for aggressive interventions such as allogeneic stem cell transplantation. Genetics is moving from being mostly a prognostic factor to becoming a multitasking decision support tool for hematologists. Physicians must pay attention to advances in molecular hematology as it will soon be accessible and influential for most of our patients.

  6. Genetic testing for hypertrophic cardiomyopathy: ongoing voyage from exploration to clinical exploitation

    Directory of Open Access Journals (Sweden)

    Iacopo Olivotto

    2011-07-01

    Full Text Available More than two decades have elapsed since the discovery that sarcomere gene defects cause familial hypertrophic cardiomyopathy (HCM. Since then, genetic testing in HCM has developed and expanded, and is now widely available as a potential clinical service in the Western countries. In the meantime, however, the cross-talk between geneticists and clinicians has developed slowly, and still remains unstandardized, with modalities of interaction and degree of mutual comprehension that vary wildly in various settings. In addition, clinicians often question the clinical utility of genetic testing in HCM patients and their families. The apparent lack of practical benefit, in the face of considerable costs, has long hindered large-scale diffusion of genetic testing, particularly in developing countries, and still accounts for understandable (but not always justifiable resistance on the part of the physicians. However, such resistance is in contrast with considerable evidence supporting a role for molecular diagnosis in tailoring management for HCM patients. We here review several sound clinical reasons in favour of systematic genetic testing in HCM, ranging from identification of complex genotypes, heralding severe disease expression and outcome, to the added benefit of multidisciplinary genetic teamwork, enhancing awareness towards inheritable diseases in the cardiology community. We hope to show that to underestimate the clinical potential of genetic testing in HCM, and to defer its implementation until more advanced knowledge becomes available, is to lose an important opportunity for present improvement in care.

  7. Frequency and clinical significance of erythrocyte genetic abnormalities in Omanis.

    OpenAIRE

    White, J. M.; Christie, B S; Nam, D; S. Daar; Higgs, D R

    1993-01-01

    The frequencies of four malaria associated erythrocyte genetic abnormalities have been established in 1000 Omani subjects. They are: homozygous alpha+ thalassaemia (-alpha/-alpha) 0.45; high Hb A2 beta thalassaemia trait 0.015; sickle trait (Hb A/S) 0.061; and glucose 6 phosphate dehydrogenase deficiency (Gd-): males 0.27, females 0.11. From our data the alpha+ (-alpha/) thal gene (confirmed by Southern blotting) is pandemic in this population. Moreover, in spite of the very high frequency of...

  8. Clinical and laboratory investigation of allergy to genetically modified foods.

    OpenAIRE

    Bernstein, Jonathan A.; Bernstein, I Leonard; Bucchini, Luca; Goldman, Lynn R.; Robert G Hamilton; Lehrer, Samuel; Rubin, Carol; Sampson, Hugh A.

    2003-01-01

    Technology has improved the food supply since the first cultivation of crops. Genetic engineering facilitates the transfer of genes among organisms. Generally, only minute amounts of a specific protein need to be expressed to obtain the desired trait. Food allergy affects only individuals with an abnormal immunologic response to food--6% of children and 1.5-2% of adults in the United States. Not all diseases caused by food allergy are mediated by IgE. A number of expert committees have advise...

  9. Facial emotion perception differs in young persons at genetic and clinical high-risk for psychosis.

    Science.gov (United States)

    Kohler, Christian G; Richard, Jan A; Brensinger, Colleen M; Borgmann-Winter, Karin E; Conroy, Catherine G; Moberg, Paul J; Gur, Ruben C; Gur, Raquel E; Calkins, Monica E

    2014-05-15

    A large body of literature has documented facial emotion perception impairments in schizophrenia. More recently, emotion perception has been investigated in persons at genetic and clinical high-risk for psychosis. This study compared emotion perception abilities in groups of young persons with schizophrenia, clinical high-risk, genetic risk and healthy controls. Groups, ages 13-25, included 24 persons at clinical high-risk, 52 first-degree relatives at genetic risk, 91 persons with schizophrenia and 90 low risk persons who completed computerized testing of emotion recognition and differentiation. Groups differed by overall emotion recognition abilities and recognition of happy, sad, anger and fear expressions. Pairwise comparisons revealed comparable impairments in recognition of happy, angry, and fearful expressions for persons at clinical high-risk and schizophrenia, while genetic risk participants were less impaired, showing reduced recognition of fearful expressions. Groups also differed for differentiation of happy and sad expressions, but differences were mainly between schizophrenia and control groups. Emotion perception impairments are observable in young persons at-risk for psychosis. Preliminary results with clinical high-risk participants, when considered along findings in genetic risk relatives, suggest social cognition abilities to reflect pathophysiological processes involved in risk of schizophrenia. PMID:24582775

  10. Common genetic variants associated with telomere length confer risk for neuroblastoma and other childhood cancers.

    Science.gov (United States)

    Walsh, Kyle M; Whitehead, Todd P; de Smith, Adam J; Smirnov, Ivan V; Park, Minsun; Endicott, Alyson A; Francis, Stephen S; Codd, Veryan; Samani, Nilesh J; Metayer, Catherine; Wiemels, Joseph L

    2016-06-01

    Aberrant telomere lengthening is an important feature of cancer cells in adults and children. In addition to somatic mutations, germline polymorphisms in telomere maintenance genes impact telomere length. Whether these telomere-associated polymorphisms affect risk of childhood malignancies remains largely unexplored. We collected genome-wide data from three groups with pediatric malignancies [neuroblastoma (N = 1516), acute lymphoblastic leukemia (ALL) (N = 958) and osteosarcoma (N = 660)] and three control populations (N = 6892). Using case-control comparisons, we analyzed eight single nucleotide polymorphisms (SNPs) in genes definitively associated with interindividual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208 and RTEL1 Six of these SNPs were associated (P < 0.05) with neuroblastoma risk, one with leukemia risk and one with osteosarcoma risk. The allele associated with longer LTL increased cancer risk for all these significantly associated SNPs. Using a weighted linear combination of the eight LTL-associated SNPs, we observed that neuroblastoma patients were predisposed to longer LTL than controls, with each standard deviation increase in genotypically estimated LTL associated with a 1.15-fold increased odds of neuroblastoma (95%CI = 1.09-1.22; P = 7.9×10(-7)). This effect was more pronounced in adolescent-onset neuroblastoma patients (OR = 1.46; 95%CI = 1.03-2.08). A one standard deviation increase in genotypically estimated LTL was more weakly associated with osteosarcoma risk (OR = 1.10; 95%CI = 1.01-1.19; P = 0.017) and leukemia risk (OR = 1.07; 95%CI = 1.00-1.14; P = 0.044), specifically for leukemia patients who relapsed (OR = 1.19; 95%CI = 1.01-1.40; P = 0.043). These results indicate that genetic predisposition to longer LTL is a newly identified risk factor for neuroblastoma and potentially for other cancers of childhood. PMID:27207662

  11. A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical Trials.

    Science.gov (United States)

    Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T; Wang, Chen; Heflin, Jeff; Chute, Christopher G

    2015-01-01

    Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials. PMID:26306257

  12. Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and management

    OpenAIRE

    Milani, D.; F. Manzoni; Pezzani, L; P. Ajmone; C. Gervasini; F. Menni; ESPOSITO, S.

    2015-01-01

    Background Rubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal dominant genetic disease, with an estimated prevalence of one case per 125,000 live births. RSTS is characterized by typical facial features, microcephaly, broad thumbs and first toes, intellectual disability, and postnatal growth retardation. However, no standard diagnostic criteria are available for RSTS. In this review, we summarized the clinical features and genetic basis of RSTS and highlighted areas for future st...

  13. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma

    OpenAIRE

    Van Allen, Eliezer M.; Wagle, Nikhil; Sucker, Antje; Treacy, Daniel; Johannessen, Cory; Goetz, Eva M.; Place, Chelsea S.; Taylor-Weiner, Amaro; Whittaker, Steven; Kryukov, Gregory; Hodis, Eran; Rosenberg, Mara; McKenna, Aaron; Cibulskis, Kristian; Farlow, Deborah

    2013-01-01

    Most patients with BRAFV600 metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole exome sequencing on formalin-fixed, paraffin embedded (FFPE) tumors from 45 patients with BRAFV600 metastatic melanoma who received vemurafenib or dabrafenib monotherapy. Genetic alterations in known or putative RAF inhibitor resistance gene...

  14. Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis

    OpenAIRE

    Kaltwasser, J; Werner, E; Schalk, K; Hansen, C.; Gottschalk, R; Seidl, C.

    1998-01-01

    Background—Black tea is known to be a potent inhibitor of intestinal absorption of non-haem iron at least in healthy subjects. 
Aims—To investigate this effect in patients with genetic haemochromatosis, and, more importantly, the effect of regular tea drinking on the accumulation of storage iron in these patients over one year. 
Patients—Investigations were carried out on 18 patients with clinically proven genetic haemochromatosis. For the study of storage iron accumulation, th...

  15. Impact of genetic polymorphisms on clinical response to antithrombotics

    OpenAIRE

    Lanham, Kena J; Oestreich, Julie H; Dunn, Steven P.; et al

    2010-01-01

    Kena J Lanham1,2, Julie H Oestreich3, Steven P Dunn1,2, Steven R Steinhubl41Pharmacy Services, UK HealthCare, University of Kentucky, Lexington, Kentucky, USA; 2Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA; 3Department of Pharmacy Practice, College of Pharmacy, University of Nebraska, Omaha, Nebraska, USA; 4The Medicines Company, Zurich, Switzerland and The Geisinger Clinic, Danville, Pennsylvania, USAAbstract: Antithrombot...

  16. Combined clinical and genetic testing algorithm for cervical cancer diagnosis

    OpenAIRE

    Liou, Yu-Ligh; Zhang, Tao-Lan; Yan, Tian; Yeh, Ching-Tung; Kang, Ya-Nan; Cao, Lanqin; Wu, Nayiyuan; Chang, Chi-Feng; Wang, Huei-Jen; Yen, Carolyn; Chu, Tang-Yuan; Zhang, Yi; Zhang, Yu; Zhou, Honghao

    2016-01-01

    Background Opportunistic screening in hospitals is widely used to effectively reduce the incidence rate of cervical cancer in China and other developing countries. This study aimed to identify clinical risk factor algorithms that combine gynecologic examination and molecular testing (paired box gene 1 (PAX1) or zinc finger protein 582 (ZNF582) methylation or HPV16/18) results to improve diagnostic accuracy. Methods The delta Cp of methylated PAX1 and ZNF582 was obtained via quantitative methy...

  17. Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study.

    Science.gov (United States)

    Halbach, Nicky; Smeets, Eric E; Julu, Peter; Witt-Engerström, Ingegerd; Pini, Giorgio; Bigoni, Stefania; Hansen, Stig; Apartopoulos, Flora; Delamont, Robert; van Roozendaal, Kees; Scusa, Maria F; Borelli, Paolo; Candel, Math; Curfs, Leopold

    2016-09-01

    Many studies have attempted to establish the genotype-phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well-defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype-phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non-invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence-based management in RTT. © 2016 Wiley Periodicals, Inc. PMID:27354166

  18. Connection between Genetic and Clinical Data in Bipolar Disorder

    DEFF Research Database (Denmark)

    Mellerup, Erling; Andreassen, Ole; Bennike, Bente;

    2012-01-01

    Complex diseases may be associated with combinations of changes in DNA, where the single change has little impact alone. In a previous study of patients with bipolar disorder and controls combinations of SNP genotypes were analyzed, and four large clusters of combinations were found to be...... significantly associated with bipolar disorder. It has now been found that these clusters may be connected to clinical data....

  19. Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution

    OpenAIRE

    Li, Rui; Li, Hailin; Yan, Wei; Yang, Pei; Bao, Zhaoshi; Zhang, Chuanbao; Jiang, Tao; You, Yongping

    2015-01-01

    Glioblastoma multiforme (GBM) is classified into primary (pGBM) or secondary (sGBM) based on clinical progression. However, there are some limits to this classification for insight into genetically and clinically distinction between pGBM and sGBM. The aim of this study is to characterize pGBM and sGBM associating with differential molecular subtype distribution. Whole transcriptome sequencing data was used to assess the distribution of molecular subtypes and genetic alterations in 88 pGBM and...

  20. Attitudes towards abortion among trainees in obstetrics/gynecology and clinical genetics

    DEFF Research Database (Denmark)

    Ingerslev, Marie Diness; Diness, Birgitte Rode; Norup, Michael Slott

    2012-01-01

    This study aimed to provide knowledge about attitudes towards abortion among Danish physicians in training in the specialties of obstetrics/gynecology and clinical genetics. The study was a questionnaire survey among trainees in these specialties. Ninety-six responded. Trainees in clinical genetics...... were more pro-abortion than those in obstetrics/gynecology (p=0.04). Of the respondents, 30 versus 48% found working with early and late abortions unpleasant. Nearly half agreed that they had chosen their specialty despite having to counsel and treat women having abortions. Twenty-one percent agreed...

  1. Ectodermal dysplasias: a new clinical-genetic classification

    OpenAIRE

    Priolo, M; Lagana, C.

    2001-01-01

    The ectodermal dysplasias (EDs) are a large and complex nosological group of diseases, first described by Thurnam in 1848. In the last 10 years more than 170 different pathological clinical conditions have been recognised and defined as EDs, all sharing in common anomalies of the hair, teeth, nails, and sweat glands. Many are associated with anomalies in other organs and systems and, in some conditions, with mental retardation.
The anomalies affecting the epidermis and epidermal appendages ar...

  2. Genetic analysis and clinical features of familial hypokalemic periodic paralysis

    Directory of Open Access Journals (Sweden)

    Hui-li ZHANG

    2014-06-01

    Full Text Available Background To investigate the gene mutation and clinical features of hypokalemic periodic paralysis (HypoPP in a Han family. Methods Mutation analyses of CACNA1S, SCN4A and KCNE3 gene were screened by DNA direct sequencing in the proband (Ⅲ3. Then, other patients and one asymptomatic relative were tested for the mutation detected in the proband before. Besides, clinical information was collected and analyzed carefully so as to detect whether the mutations were responsible for HypoPP.  Results KCNE3 gene was not detected in the propositus (Ⅲ 3. Mutations of IVS25-194C/T in CACNA1S gene were detected in the propositus (Ⅲ 3 and other patients (Ⅱ 1, Ⅲ 4, Ⅳ 3, while it was not detected in the asymptomatic relative (Ⅲ1. Given that it was an intron mutation, we presumed that it was not responsible for HypoPP in this family. In addition, mutations of IVS18-130G/A in SCN4A gene were detected in all patients (except for Ⅰ1 and asymptomatic relative (Ⅲ 1. Since it was an intron mutation and it was detected in symptomatic or asymptomatic members simultaneously, we also presumed that it was not responsible for HypoPP in this family. Interestingly, a missense mutation (V662I of c.1984G > A in exon 12 of SCN4A gene was detected in the proband (Ⅲ 3 and asymptomatic relative (Ⅲ 1. However, it was not detected in other symptomatic members ( Ⅱ 1, Ⅲ 4, Ⅳ 3. Based on clinical information and bioinformatics, we presumed that it was not causative mutation for the disease in this pedigree.  Conclusions This pedigree research enriched the data of gene mutation and clinical features of HypoPP in China. Besides for gene KCNE3, CACNA1S and SCN4A, other gene mutations accounted for HypoPP in the Han family should be further studied. doi: 10.3969/j.issn.1672-6731.2014.06.006

  3. 1st international conference on the clinical use of tomotherapy, October 17-18, 2008 Munich. Abstracts

    International Nuclear Information System (INIS)

    The first international conference on the clinical use of tomotherapy was hosted by the Department of Radiation Oncology of the ''Technische Univer-sita't Munchen'' on October 17 and 18, 2008. Over 170 radiation oncologists and physicists from 16 countries discussed improved treatment options offered by the tomotherapy technology.Thirty-five presentations and twenty-one posters covered a variety of indications in different tumor entities as well as physics implementation and quality assurance of this new technique.Notable conference lectures included the presentation of a predictive model of tumor response in lung cancer based on daily MV-CT imaging. The model may allow determination of effective adaptive radiotherapy strategies early in the course of radiation treatment. New techniques were presented to further reduce treatment time and to decrease the dose outside the planning target volume (''dynamic jaws',' ''dynamic couch''). Treatment protocols were discussed including a study directed from the University Clinic Essen in a method for treating multiple brain metastases with a simultaneous integrated boost technique applying 10x5 Gy within the metastases. This strategy is going to be evaluated against whole-brain radiotherapy with 10 x 3 Gy in a randomized phase II trial. Another interesting concept was the use of tomotherapy to treat the whole abdominal volume for ovarian cancer while sparing liver, kidneys and bone marrow. Tomotherapy proved its feasibility in the treatment of mesothelioma, a clinically challenging disease in which therapy options were previously limited due to complications of organs at risk. Many presentations discussed the application of tomotherapy in complex cases including large-volume lymphoma where avoidance of critical structures may lead to a reduction of long-term late toxicity. Presentations of user groups from both the USA and Europe discussed how these groups have shared and developed knowledge of clinical tomotherapy experience

  4. Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites

    Directory of Open Access Journals (Sweden)

    Hunt Paul

    2010-09-01

    Full Text Available Abstract Background Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, Plasmodium chabaudi. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, P. falciparum. Results A lineage of isogenic in vivo drug-selected mutant P. chabaudi parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an in vivo artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (Illumina® Solexa defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme. Conclusions This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations.

  5. Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites

    KAUST Repository

    Hunt, Paul

    2010-09-16

    Background: Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, Plasmodium chabaudi. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, P. falciparum.Results: A lineage of isogenic in vivo drug-selected mutant P. chabaudi parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an in vivo artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (IlluminaSolexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme.Conclusions: This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations. 2010 Hunt et al; licensee BioMed Central Ltd.

  6. Atlas of the clinical genetics of human dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Haas, Jan; Frese, Karen S; Peil, Barbara;

    2015-01-01

    AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these......, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted...... disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is...

  7. The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe

    Science.gov (United States)

    Hastings, Ros; de Wert, Guido; Fowler, Brian; Krawczak, Michael; Vermeulen, Eric; Bakker, Egbert; Borry, Pascal; Dondorp, Wybo; Nijsingh, Niels; Barton, David; Schmidtke, Jörg; van El, Carla G; Vermeesch, Joris; Stol, Yrrah; Carmen Howard, Heidi; Cornel, Martina C

    2012-01-01

    The arrival of new genetic technologies that allow efficient examination of the whole human genome (microarray, next-generation sequencing) will impact upon both laboratories (cytogenetic and molecular genetics in the first instance) and clinical/medical genetic services. The interpretation of analytical results in terms of their clinical relevance and the predicted health status poses a challenge to both laboratory and clinical geneticists, due to the wealth and complexity of the information obtained. There is a need to discuss how to best restructure the genetic services logistically and to determine the clinical utility of genetic testing so that patients can receive appropriate advice and genetic testing. To weigh up the questions and challenges of the new genetic technologies, the European Society of Human Genetics (ESHG) held a series of workshops on 10 June 2010 in Gothenburg. This was part of an ESHG satellite symposium on the ‘Changing landscape of genetic testing', co-organized by the ESHG Genetic Services Quality and Public and Professional Policy Committees. The audience consisted of a mix of geneticists, ethicists, social scientists and lawyers. In this paper, we summarize the discussions during the workshops and present some of the identified ways forward to improve and adapt the genetic services so that patients receive accurate and relevant information. This paper covers ethics, clinical utility, primary care, genetic services and the blurring boundaries between healthcare and research. PMID:22453292

  8. Clinical endpoints for developing pharmaceuticals to manage patients with sporadic or genetic risk of colorectal cancer

    OpenAIRE

    Rial, Nathaniel S; Zell, Jason A.; Cohen, Alfred M.; Gerner, Eugene W.

    2012-01-01

    To reduce the morbidity and mortality from colorectal cancer, current clinical practice focuses on screening for early detection and polypectomy as a form of secondary prevention, complemented with surgical interventions when appropriate. No pharmaceutical agent is currently approved for use in clinical practice for the management of patients with risk of colorectal cancer. This article will review earlier attempts to develop pharmaceuticals for use in managing patients with sporadic or genet...

  9. Human genetics after the bomb: Archives, clinics, proving grounds and board rooms.

    Science.gov (United States)

    Lindee, Susan

    2016-02-01

    In this paper I track the history of post-1945 human genetics and genomics emphasizing the importance of ideas about risk to the scientific study and medical management of human heredity. Drawing on my own scholarship as it is refracted through important new work by other scholars both junior and senior, I explore how radiation risk and then later disease risk mattered to the development of genetics and genomics, particularly in the United States. In this context I excavate one of the central ironies of post-war human genetics: while studies of DNA as the origin and cause of diseases have been lavishly supported by public institutions and private investment around the world, the day-to-day labor of intensive clinical innovation has played a far more important role in the actual human experience of genetic disease and genetic risk for affected families. This has implications for the archival record, where clinical interactions are less readily accessible to historians. This paper then suggests that modern genomics grew out of radiation risk; that it was and remains a risk assessment science; that it is temporally embedded as a form of both prediction and historical reconstruction; and that it has become a big business focused more on risk and prediction (which can be readily marketed) than on effective clinical intervention. PMID:26456508

  10. Carnitine-acylcarnitine translocase deficiency, clinical, biochemical and genetic aspects.

    Science.gov (United States)

    Rubio-Gozalbo, M E; Bakker, J A; Waterham, H R; Wanders, R J A

    2004-01-01

    The carnitine-acylcarnitine translocase (CACT) is one of the components of the carnitine cycle. The carnitine cycle is necessary to shuttle long-chain fatty acids from the cytosol into the intramitochondrial space where mitochondrial beta-oxidation of fatty acids takes place. The oxidation of fatty acids yields acetyl-coenzyme A (CoA) units, which may either be degraded to CO(2) and H(2)O in the citric acid cycle to produce ATP or converted into ketone bodies which occurs in liver and kidneys. Metabolic consequences of a defective CACT are hypoketotic hypoglycaemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and an abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical signs and symptoms in CACT deficient patients, are a combination of energy depletion and endogenous toxicity. The predominantly affected organs are brain, heart and skeletal muscle, and liver, leading to neurological abnormalities, cardiomyopathy and arrythmias, skeletal muscle damage and liver dysfunction. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate. However, presentations at a later age with a milder phenotype have also been reported. The therapeutic approach is the same as in other long-chain fatty acid disorders and includes intravenous glucose (+/- insulin) administration to maximally inhibit lipolysis and subsequent fatty acid oxidation during the acute deterioration, along with other measures such as ammonia detoxification, depending on the clinical features. Long-term strategy consists of avoidance of fasting with frequent meals and a special diet with restriction of long-chain fatty acids. Due to the extremely low free carnitine concentrations, carnitine supplementation is often needed. Acylcarnitine profiling in plasma is the assay of choice for the diagnosis at a metabolite level

  11. Effects of Anxiety on Novice Genetic Counseling Students' Experience of Supervised Clinical Rotations.

    Science.gov (United States)

    MacFarlane, Ian M; McCarthy Veach, Pat; Grier, Janelle E; Meister, Derek J; LeRoy, Bonnie S

    2016-08-01

    Supervised clinical experiences with patients comprise a critical component of genetic counseling student education. Previous research has found genetic counseling students tend to be more anxiety prone than the general population, and anxiety related to supervision has been found in genetic counseling and related fields. The present study investigated how anxiety affects the experience of supervision for genetic counseling students. Second year genetic counseling students were invited to participate through email invitations distributed via training directors of the 33 programs accredited at the time of the study by the American Board of Genetic Counseling. An initial online survey contained the trait scale of the State-Trait Anxiety Inventory to estimate anxiety proneness in this population and an invitation to participate in a 45-minute semi-structured phone interview focusing on students' experiences of supervision during their clinical rotations. High and low trait anxiety groups were created using STAI scores, and the groups' interview responses were compared using consensual qualitative research methodology (CQR; Hill 2012). The high anxiety group was more likely to describe problematic supervisory relationships, appreciate the supervisor's ability to help them when they get stuck in sessions, and feel their anxiety had a negative effect on their performance in general and in supervision. Common themes included supervisors' balancing support and guidance, the importance of feedback, ego-centric responses, and supervisors as focal points. The results of the present study are largely consistent with current literature. Further research findings and research, practice, and training recommendations are provided. PMID:27098419

  12. Clinical validity and utility of genetic risk scores in prostate cancer.

    Science.gov (United States)

    Helfand, Brian T; Kearns, James; Conran, Carly; Xu, Jianfeng

    2016-01-01

    Current issues related to prostate cancer (PCa) clinical care (e.g., over-screening, over-diagnosis, and over-treatment of nonaggressive PCa) call for risk assessment tools that can be combined with family history (FH) to stratify disease risk among men in the general population. Since 2007, genome-wide association studies (GWASs) have identified more than 100 SNPs associated with PCa susceptibility. In this review, we discuss (1) the validity of these PCa risk-associated SNPs, individually and collectively; (2) the various methods used for measuring the cumulative effect of multiple SNPs, including genetic risk score (GRS); (3) the adequate number of SNPs needed for risk assessment; (4) reclassification of risk based on evolving numbers of SNPs used to calculate genetic risk, (5) risk assessment for men from various racial groups, and (6) the clinical utility of genetic risk assessment. In conclusion, data available to date support the clinical validity of PCa risk-associated SNPs and GRS in risk assessment among men with or without FH. PCa risk-associated SNPs are not intended for diagnostic use; rather, they should be used the same way as FH. Combining GRS and FH can significantly improve the performance of risk assessment. Improved risk assessment may have important clinical utility in targeted PCa testing. However, clinical trials are urgently needed to evaluate this clinical utility as well as the acceptance of GRS by patients and physicians. PMID:27297129

  13. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey.

    Science.gov (United States)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian; Drzewiecki, Krzysztof T; Prause, Jan U; Heegaard, Steffen

    2016-06-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma). PMID:27004972

  14. Multiple trait genetic evaluation of clinical mastitis in three dairy cattle breeds.

    Science.gov (United States)

    Govignon-Gion, A; Dassonneville, R; Baloche, G; Ducrocq, V

    2016-04-01

    In 2010, a routine genetic evaluation on occurrence of clinical mastitis in three main dairy cattle breeds-- Montbéliarde (MO), Normande (NO) and Holstein (HO)--was implemented in France. Records were clinical mastitis events reported by farmers to milk recording technicians and the analyzed trait was the binary variable describing the occurrence of a mastitis case within the first 150 days of the first three lactations. Genetic parameters of clinical mastitis were estimated for the three breeds. Low heritability estimates were found: between 2% and 4% depending on the breed. Despite its low heritability, the trait exhibits genetic variation so efficient genetic improvement is possible. Genetic correlations with other traits were estimated, showing large correlations (often>0.50, in absolute value) between clinical mastitis and somatic cell score (SCS), longevity and some udder traits. Correlation with milk yield was moderate and unfavorable (ρ=0.26 to 0.30). High milking speed was genetically associated with less mastitis in MO (ρ=-0.14) but with more mastitis in HO (ρ=0.18). A two-step approach was implemented for routine evaluation: first, a univariate evaluation based on a linear animal model with permanent environment effect led to pre-adjusted records (defined as records corrected for all non-genetic effects) and associated weights. These data were then combined with similar pre-adjusted records for others traits in a multiple trait BLUP animal model. The combined breeding values for clinical mastitis obtained are the official (published) ones. Mastitis estimated breeding values (EBV) were then combined with SCSs EBV into an udder health index, which receives a weight of 14.5% to 18.5% in the French total merit index (ISU) of the three breeds. Interbull genetic correlations for mastitis occurrence were very high (ρ=0.94) with Nordic countries, where much stricter recording systems exist reflecting a satisfactory quality of phenotypes as reported by the

  15. Erythropoietin in the General Population : Reference Ranges and Clinical, Biochemical and Genetic Correlates

    NARCIS (Netherlands)

    Grote Beverborg, Niels; Verweij, Niek; Klip, IJsbrand T.; van der Wal, Haye H.; Voors, Adriaan A.; van Veldhuisen, Dirk J.; Gansevoort, Ron T.; Bakker, Stephan J. L.; van der Harst, Pim; van der Meer, Peter

    2015-01-01

    Background Although erythropoietin has been used for decades in the treatment of anemia, data regarding endogenous levels in the general population are scarce. Therefore, we determined erythropoietin reference ranges and its clinical, biochemical and genetic associations in the general population. M

  16. Alpha-mannosidosis - a review of genetic, clinical findings and options of treatment

    DEFF Research Database (Denmark)

    Borgwardt, Line; Lund, Allan Meldgaard; Dali, Christine I.

    2014-01-01

    Alpha-mannosidosis (OMIM 248500) is a rare, autosomal recessive, multisystemic, progressive lysosomal storage disorder caused by a deficiency of alpha-mannosidase. It has been described in humans, cattle, domestic cats, mice and guinea pigs. In humans, alpha-mannosidosis results in progressive...... alpha-mannosidosis. The pathology, genetics and clinical pictures, including impairments in the activity of daily living are discussed....

  17. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Blom, M T; van Hoeijen, D A; Bardai, A;

    2014-01-01

    INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA......-reviewed journals and presented at relevant scientific symposia....

  18. Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic

    Directory of Open Access Journals (Sweden)

    Samantha B. Foley

    2015-01-01

    Full Text Available Despite the potential of whole-genome sequencing (WGS to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176 and those without (n = 82. Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500 in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS. Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks.

  19. 76 FR 18227 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of...

    Science.gov (United States)

    2011-04-01

    ... in the Federal Register of February 7, 2011 (76 FR 6623). In the notice, FDA requested public comment.... Background In the Federal Register of February 7, 2011 (76 FR 6623), FDA published a notice announcing a... HUMAN SERVICES Food and Drug Administration Molecular and Clinical Genetics Panel of the Medical...

  20. Clinical, biological and genetic analysis of anorchia in 26 boys.

    Directory of Open Access Journals (Sweden)

    Raja Brauner

    Full Text Available BACKGROUND: Anorchia is defined as the absence of testes in a 46,XY individual with a male phenotype. The cause is unknown. METHODS: We evaluated the clinical and biological presentation, and family histories of 26 boys with anorchia, and sequenced their SRY, NR5A1, INSL3, MAMLD1 genes and the T222P variant for LGR8. RESULTS: No patient had any associated congenital anomaly. At birth, testes were palpable bilaterally or unilaterally in 13 cases and not in 7; one patient presented with bilateral testicular torsion immediately after birth. The basal plasma concentrations of anti-Müllerian hormone (AMH, n = 15, inhibin B (n = 7 and testosterone (n = 19 were very low or undetectable in all the patients evaluated, as were the increases in testosterone after human chorionic gonadotropin (hCG, n = 12. The basal plasma concentrations of follicle stimulating hormone (FSH were increased in 20/25, as was that of luteinising hormone in 10/22 cases. Family members of 7/26 cases had histories of primary ovarian failure in the mother (n = 2, or sister 46,XX, together with fetal malformations of the only boy with microphallus and secondary foot edema (n = 1, secondary infertility in the father (n = 2, or cryptorchidism in first cousins (n = 2. The sequences of all the genes studied were normal. CONCLUSION: Undetectable plasma concentrations of AMH and inhibin B and an elevated plasma FSH, together with 46,XY complement are sufficient for diagnosis of anorchia. The hCG test is unnecessary. NR5A1 and other genes implicated in gonadal development and testicle descent were not mutated, which suggests that other genes involved in these developments contribute to the phenotypes.

  1. Genetics of Type 2 Diabetes: Insights into the Pathogenesis and Its Clinical Application

    Directory of Open Access Journals (Sweden)

    Xue Sun

    2014-01-01

    Full Text Available With rapidly increasing prevalence, diabetes has become one of the major causes of mortality worldwide. According to the latest studies, genetic information makes substantial contributions towards the prediction of diabetes risk and individualized antidiabetic treatment. To date, approximately 70 susceptibility genes have been identified as being associated with type 2 diabetes (T2D at a genome-wide significant level (P<5×10-8. However, all the genetic loci identified so far account for only about 10% of the overall heritability of T2D. In addition, how these novel susceptibility loci correlate with the pathophysiology of the disease remains largely unknown. This review covers the major genetic studies on the risk of T2D based on ethnicity and briefly discusses the potential mechanisms and clinical utility of the genetic information underlying T2D.

  2. Improving Decision Making about Genetic Testing in the Clinic: An Overview of Effective Knowledge Translation Interventions

    Science.gov (United States)

    Légaré, France; Robitaille, Hubert; Gane, Claire; Hébert, Jessica; Labrecque, Michel; Rousseau, François

    2016-01-01

    Background Knowledge translation (KT) interventions are attempts to change behavior in keeping with scientific evidence. While genetic tests are increasingly available to healthcare consumers in the clinic, evidence about their benefits is unclear and decisions about genetic testing are thus difficult for all parties. Objective We sought to identify KT interventions that involved decisions about genetic testing in the clinical context and to assess their effectiveness for improving decision making in terms of behavior change, increased knowledge and wellbeing. Methods We searched for trials assessing KT interventions in the context of genetic testing up to March 2014 in all systematic reviews (n = 153) published by two Cochrane review groups: Effective Practice and Organisation of Care (EPOC) and Consumers and Communication. Results We retrieved 2473 unique trials of which we retained only 28 (1%). Two EPOC reviews yielded two trials of KT interventions: audit and feedback (n = 1) and educational outreach (n = 1). Both targeted health professionals and the KT intervention they assessed was found to be effective. Four Consumers and Communication reviews yielded 26 trials: decision aids (n = 15), communication of DNA-based disease risk estimates (n = 7), personalized risk communication (n = 3) and mobile phone messaging (n = 1). Among these, 25 trials targeted only health consumers or patients and the KT interventions were found to be effective in four trials, partly effective in seven, and ineffective in four. Lastly, only one trial targeted both physicians and patients and was found to be effective. Conclusions More research on the effectiveness of KT interventions regarding genetic testing in the clinical context may contribute to patients making informed value-based decisions and drawing the maximum benefit from clinical applications of genetic and genomic innovations. PMID:26938633

  3. Genetic Counseling Supervisors' Self-Efficacy for Select Clinical Supervision Competencies.

    Science.gov (United States)

    Finley, Sabra Ledare; Veach, Pat McCarthy; MacFarlane, Ian M; LeRoy, Bonnie S; Callanan, Nancy

    2016-04-01

    Supervision is a primary instructional vehicle for genetic counseling student clinical training. Approximately two-thirds of genetic counselors report teaching and education roles, which include supervisory roles. Recently, Eubanks Higgins and colleagues published the first comprehensive list of empirically-derived genetic counseling supervisor competencies. Studies have yet to evaluate whether supervisors possess these competencies and whether their competencies differ as a function of experience. This study investigated three research questions: (1) What are genetic counselor supervisors' perceptions of their capabilities (self-efficacy) for a select group of supervisor competencies?, (2) Are there differences in self-efficacy as a function of their supervision experience or their genetic counseling experience, and 3) What training methods do they use and prefer to develop supervision skills? One-hundred thirty-one genetic counselor supervisors completed an anonymous online survey assessing demographics, self-efficacy (self-perceived capability) for 12 goal setting and 16 feedback competencies (Scale: 0-100), competencies that are personally challenging, and supervision training experiences and preferences (open-ended). A MANOVA revealed significant positive effects of supervision experience but not genetic counseling experience on participants' self-efficacy. Although mean self-efficacy ratings were high (>83.7), participant comments revealed several challenging competencies (e.g., incorporating student's report of feedback from previous supervisors into goal setting, and providing feedback about student behavior rather than personal traits). Commonly preferred supervision training methods included consultation with colleagues, peer discussion, and workshops/seminars. PMID:26242467

  4. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.

    Science.gov (United States)

    2003-06-15

    As the leading organization representing cancer specialists involved in patient care and clinical research, the American Society of Clinical Oncology (ASCO) reaffirms its commitment to integrating cancer risk assessment and management, including molecular analysis of cancer predisposition genes, into the practice of oncology and preventive medicine. The primary goal of this effort is to foster expanded access to, and continued advances in, medical care provided to patients and families affected by hereditary cancer syndromes. The 1996 ASCO Statement on Genetic Testing for Cancer Susceptibility set forth specific recommendations relating to clinical practice, research needs, educational opportunities, requirement for informed consent, indications for genetic testing, regulation of laboratories, and protection from discrimination, as well as access to and reimbursement for cancer genetics services. In updating this Statement, ASCO endorses the following principles: Indications for Genetic Testing: ASCO recommends that genetic testing be offered when 1) the individual has personal or family history features suggestive of a genetic cancer susceptibility condition, 2) the test can be adequately interpreted, and 3) the results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer. ASCO recommends that genetic testing only be done in the setting of pre- and post-test counseling, which should include discussion of possible risks and benefits of cancer early detection and prevention modalities. Special Issues in Testing Children for Cancer Susceptibility: ASCO recommends that the decision to offer testing to potentially affected children should take into account the availability of evidence-based risk-reduction strategies and the probability of developing a malignancy during childhood. Where risk-reduction strategies are available or cancer predominantly develops in childhood, ASCO believes that

  5. A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies

    Science.gov (United States)

    Leventer, Richard J.; van der Knaap, Marjo S.; van Hove, Johan; Pizzino, Amy; McNeill, Nathan H.; Helman, Guy; Simons, Cas; Schmidt, Johanna L.; Rizzo, William B.

    2015-01-01

    Leukodystrophies (LD) and genetic leukoencephalopathies (gLE) are disorders that result in white matter abnormalities in the central nervous system (CNS). Magnetic resonance (MR) imaging (MRI) has dramatically improved and systematized the diagnosis of LDs and gLEs, and in combination with specific clinical features, such as Addison's disease in Adrenoleukodystrophy or hypodontia in Pol-III related or 4H leukodystrophy, can often resolve a case with a minimum of testing. The diagnostic odyssey for the majority LD and gLE patients, however, remains extensive – many patients will wait nearly a decade for a definitive diagnosis and at least half will remain unresolved. The combination of MRI, careful clinical evaluation and next generation genetic sequencing holds promise for both expediting the diagnostic process and dramatically reducing the number of unresolved cases. Here we present a workflow detailing the Global Leukodystrophy Initiative (GLIA) consensus recommendations for an approach to clinical diagnosis, including salient clinical features suggesting a specific diagnosis, neuroim-aging features and molecular genetic testing. We also discuss recommendations on the use of broad-spectrum next-generation sequencing in instances of ambiguous MRI or clinical findings. We conclude with a proposal for systematic trials of genome-wide agnostic testing as a first line diagnostic in LDs and gLEs given the increasing number of genes associated with these disorders. PMID:25655951

  6. 76 FR 6623 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-02-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Molecular and Clinical Genetics Panel of the Medical Devices... (FDA). The meeting will be open to the public. Name of Committee: Molecular and Clinical Genetics...

  7. Clinical and pharmacogenomic implications of genetic variation in a Southern Ethiopian population.

    Science.gov (United States)

    Tekola-Ayele, F; Adeyemo, A; Aseffa, A; Hailu, E; Finan, C; Davey, G; Rotimi, C N; Newport, M J

    2015-02-01

    Africa is home to genetically diverse human populations. We compared the genetic structure of the Wolaita ethnic population from Southern Ethiopia (WETH, n=120) with HapMap populations using genome-wide variants. We investigated allele frequencies of 443 clinically and pharmacogenomically relevant genetic variants in WETH compared with HapMap populations. We found that WETH were genetically most similar to the Kenya Maasai and least similar to the Japanese in HapMap. Variant alleles associated with increased risk of adverse reactions to drugs used for treating tuberculosis (rs1799929 and rs1495741 in NAT2), thromboembolism (rs7294, rs9923231 and rs9934438 in VKORC1), and HIV/AIDS and solid tumors (rs2242046 in SLC28A1) had significantly higher frequencies in WETH compared with African ancestry HapMap populations. Our results illustrate that clinically relevant pharmacogenomic loci display allele frequency differences among African populations. We conclude that drug dosage guidelines for important global health diseases should be validated in genetically diverse African populations. PMID:25069476

  8. The next controversy in genetic testing: clinical data as trade secrets?

    Science.gov (United States)

    Cook-Deegan, Robert; Conley, John M; Evans, James P; Vorhaus, Daniel

    2013-06-01

    Sole-source business models for genetic testing can create private databases containing information vital to interpreting the clinical significance of human genetic variations. But incomplete access to those databases threatens to impede the clinical interpretation of genomic medicine. National health systems and insurers, regulators, researchers, providers and patients all have a strong interest in ensuring broad access to information about the clinical significance of variants discovered through genetic testing. They can create incentives for sharing data and interpretive algorithms in several ways, including: promoting voluntary sharing; requiring laboratories to share as a condition of payment for or regulatory approval of laboratory services; establishing - and compelling participation in - resources that capture the information needed to interpret the data independent of company policies; and paying for sharing and interpretation in addition to paying for the test itself. US policies have failed to address the data-sharing issue. The entry of new and established firms into the European genetic testing market presents an opportunity to correct this failure. PMID:23150081

  9. Clinical and Genetic Determinants of Cardiomyopathy Risk among Hematopoietic Cell Transplantation Survivors.

    Science.gov (United States)

    Leger, Kasey J; Cushing-Haugen, Kara; Hansen, John A; Fan, Wenhong; Leisenring, Wendy M; Martin, Paul J; Zhao, Lue Ping; Chow, Eric J

    2016-06-01

    Cardiomyopathy has been recognized as a complication after hematopoietic cell transplantation (HCT). Using a nested case-cohort design, we examined the relationships between demographic, therapeutic, and selected cardiovascular disease risk factors among ≥1-year HCT survivors who developed cardiomyopathy before (n = 43) or after (n = 89) 1 year from HCT as compared to a randomly selected subcohort of survivors without cardiomyopathy (n = 444). Genomic data were available for 79 cases and 267 noncases. Clinical and genetic covariates were examined for association with the risk of early or late cardiomyopathy. Clinical risk factors associated with both early- and late-onset cardiomyopathy included anthracycline exposure ≥250 mg/m(2) and pre-existing hypertension. Among late-onset cardiomyopathy cases, the development of diabetes and ischemic heart disease further increased risk. We replicated several previously reported genetic associations among early-onset cardiomyopathy cases, including rs1786814 in CELF4, rs2232228 in HAS3, and rs17863783 in UGT1A6. None of these markers were associated with risk of late-onset cardiomyopathy. A combination of demographic, treatment, and clinical covariates predicted early-onset cardiomyopathy with reasonable accuracy (area under the curve [AUC], .76; 95% confidence interval [CI], .68 to .83), but prediction of late cardiomyopathy was poor (AUC, .59; 95% CI .53 to .67). The addition of genetic polymorphisms with marginal associations (odds ratios ≥1.3) did not enhance prediction for either early- or late-onset cardiomyopathy. Conventional cardiovascular risk factors influence the risk of both early- and late-onset cardiomyopathy in HCT survivors. Although certain genetic markers may influence the risk of early-onset disease, further work is required to validate previously reported findings and to determine how genetic information should be incorporated into clinically useful risk prediction models. PMID:26968791

  10. Autism and genetics: Clinical approach and association study with two markers of HRAS gene

    Energy Technology Data Exchange (ETDEWEB)

    Herault, J.; Petit, E.; Cherpi, C. [Laboratoire de Biochimie Medicale, Tours (France)] [and others

    1995-08-14

    Twin studies and familial aggregation studies indicate that genetic factors could play a role in infantile autism. In an earlier study, we identified a possible positive association between autism and a c-Harvey-ras (HRAS) oncogene marker at the 3{prime} end of the coding region. In an attempt to confirm this finding, we studied a larger population, well-characterized clinically and genetically. We report a positive association between autism and two HRAS markers, the 3{prime} marker used in the initial study and an additional marker in exon 1. 46 refs., 1 fig., 2 tabs.

  11. Rapid full-field OCT assessment of clinical tissue specimens (Conference Presentation)

    Science.gov (United States)

    Dalimier, Eugénie; Harms, Fabrice; Brossollet, Charles; Benoit, Emilie; Martins, Franck; Boccara, Claude A.

    2016-03-01

    FFOCT (Full Field Optical Coherence Tomography) is a novel optical technology that gives access to very high resolution tomography images of biological tissues within minutes, non-invasively. This makes it an attractive tool to bridge the gap between medical imaging modalities (MRI, ultrasound, CT) used for cancer lesion identification or targeting and histological diagnosis. Clinical tissue specimens, such as surgical cancer margins or biopsies, can potentially be assessed rapidly, by the clinician, in the aim to help him decide on the course of action. A fast FFOCT prototype was built, that provides 1cm2 images with 1 µm resolution in 1 minute, and can accommodate samples up to 50mm diameter. Specific work was carried out to implement a large sample holder, high-speed image acquisition system, optimized scanning, and accelerated GPU tiles stitching. Results obtained on breast, urology, and digestive tissues show the efficiency of the technique for the detection of cancer on clinical tissue specimens, and reinforce the clinical relevance of the technique. The technical and clinical results show that the fast FFOCT system can successfully be used for a fast assessment of cancer excision margins or biopsies providing a very valuable tool in the clinical environment.

  12. Genetic counselors' views and experiences with the clinical integration of genome sequencing.

    Science.gov (United States)

    Machini, Kalotina; Douglas, Jessica; Braxton, Alicia; Tsipis, Judith; Kramer, Kate

    2014-08-01

    In recent years, new sequencing technologies known as next generation sequencing (NGS) have provided scientists the ability to rapidly sequence all known coding as well as non-coding sequences in the human genome. As the two emerging approaches, whole exome (WES) and whole genome (WGS) sequencing, have started to be integrated in the clinical arena, we sought to survey health care professionals who are likely to be involved in the implementation process now and/or in the future (e.g., genetic counselors, geneticists and nurse practitioners). Two hundred twenty-one genetic counselors- one third of whom currently offer WES/WGS-participated in an anonymous online survey. The aims of the survey were first, to identify barriers to the implementation of WES/WGS, as perceived by survey participants; second, to provide the first systematic report of current practices regarding the integration of WES/WGS in clinic and/or research across the US and Canada and to illuminate the roles and challenges of genetic counselors participating in this process; and third to evaluate the impact of WES/WGS on patient care. Our results showed that genetic counseling practices with respect to WES/WGS are consistent with the criteria set forth in the ACMG 2012 policy statement, which highlights indications for testing, reporting, and pre/post test considerations. Our respondents described challenges related to offering WES/WGS, which included billing issues, the duration and content of the consent process, result interpretation and disclosure of incidental findings and variants of unknown significance. In addition, respondents indicated that specialty area (i.e., prenatal and cancer), lack of clinical utility of WES/WGS and concerns about interpretation of test results were factors that prevented them from offering this technology to patients. Finally, study participants identified the aspects of their professional training which have been most beneficial in aiding with the integration of

  13. Genetic profiling of intrahepatic cholangiocarcinoma and its clinical implication in targeted therapy

    Science.gov (United States)

    Xie, Diyang; Ren, Zhenggang; Fan, Jia; Gao, Qiang

    2016-01-01

    Intrahepatic cholangiocarcinoma (iCCA) is a treatment-refractory primary liver cancer with an increasing incidence and mortality worldwide in recent years. Lack of a stereotyped genetic signature and limited understanding of genomic landscape make the development of effective targeted therapies challenging. Recent application of advanced technologies such as next-generation sequencing (NGS) has broadened our understanding of genetic heterogeneity in iCCA and many potentially actionable genetic alterations have been identified. This review explores the recent advances in defining genetic alterations in iCCAs, which may present potent therapeutic targets. Chromatin remodeling genes and genes encoding isocitrate dehydrogenase and tyrosine kinase receptors as well as their downstream effectors are among the most frequently altered genes. Clinical trials testing the effect of new targeted agents on iCCA patients, especially those with the above genetic markers are under way. However, the complex interplay of environmental and evolutionary factors contributing to the genetic variability in iCCA calls for a more cautionary use of NGS in tailoring targeted regimen to the patients. Next-generation functional testing may complement NGS to execute precision medicine in future.

  14. Genetic profiling of intrahepatic cholangiocarcinoma and its clinical implication in targeted therapy.

    Science.gov (United States)

    Xie, Diyang; Ren, Zhenggang; Fan, Jia; Gao, Qiang

    2016-01-01

    Intrahepatic cholangiocarcinoma (iCCA) is a treatment-refractory primary liver cancer with an increasing incidence and mortality worldwide in recent years. Lack of a stereotyped genetic signature and limited understanding of genomic landscape make the development of effective targeted therapies challenging. Recent application of advanced technologies such as next-generation sequencing (NGS) has broadened our understanding of genetic heterogeneity in iCCA and many potentially actionable genetic alterations have been identified. This review explores the recent advances in defining genetic alterations in iCCAs, which may present potent therapeutic targets. Chromatin remodeling genes and genes encoding isocitrate dehydrogenase and tyrosine kinase receptors as well as their downstream effectors are among the most frequently altered genes. Clinical trials testing the effect of new targeted agents on iCCA patients, especially those with the above genetic markers are under way. However, the complex interplay of environmental and evolutionary factors contributing to the genetic variability in iCCA calls for a more cautionary use of NGS in tailoring targeted regimen to the patients. Next-generation functional testing may complement NGS to execute precision medicine in future. PMID:27152236

  15. Genetic Counselors' and Genetic Counseling Students' Attitudes Around the Clinical Doctorate and Other Advanced Educational Options for Genetic Counselors: A Report from the Genetic Counseling Advanced Degree Task Force.

    Science.gov (United States)

    Nagy, Rebecca; Peay, Holly; Hicks, Melissa; Kloos, Jacqueline; Westman, Rachel; Conway, Laura; Finucane, Brenda; Fitzpatrick, Jennifer; Gordon, Erynn; Ramos, Erica; Sekhon-Warren, Jaspreet; Silver, Josh; Walton, Carol; Reiser, Catherine

    2015-08-01

    Since its establishment over 40 years ago, the genetic counseling profession has grown to an estimated ~4,000 professionals in North America. While the profession has maintained the Master's degree as the entry-level and terminal degree, many other allied health professions have added advanced training pathways, such as the clinical doctorate (ClinD) either as an optional post-professional degree or required entry-level degree. Discussions regarding advanced degrees have also occurred within the genetic counseling profession, dating back to as early as the 1980s. In 2011, the Genetic Counseling Advanced Degree Task Force (GCADTF) was convened to explore the issue again, with the goal of "[engaging] all of the professional leadership organizations in the field of genetic counseling in a decision-making process about whether the profession should move to a Clinical Doctorate". As part of their work, the GCADTF surveyed practicing genetic counselors (n = 4,321) and genetic counseling students (n = 522) in the US and Canada regarding their interest in moving to the ClinD as the entry-level degree. This survey also included questions about other options for advanced training to generate data to inform future discussions around this very important professional issue. Herein, we describe the results of the survey, with particular attention to genetic counselor preferences for additional advanced education/certification opportunities and recommendations for future discussion. PMID:25352337

  16. 1st international conference on the clinical use of tomotherapy, October 17-18, 2008 Munich. Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Budach, V.; Debus, J.; Geinitz, H.; Herfarth, K.; Hinkelbein, W.; Kneschaurek, P.; Krempien, R.; Kupelian, P.; Mackie, T.R.; Molls, M.; Noel, G.; Ozsahin, M.; Ramsey, C.; Schubert, K.; Sterzing, F.; Storme, G.; Stuschke, M.; Zach, K.

    2009-01-15

    The first international conference on the clinical use of tomotherapy was hosted by the Department of Radiation Oncology of the ''Technische Univer-sita't Munchen'' on October 17 and 18, 2008. Over 170 radiation oncologists and physicists from 16 countries discussed improved treatment options offered by the tomotherapy technology.Thirty-five presentations and twenty-one posters covered a variety of indications in different tumor entities as well as physics implementation and quality assurance of this new technique.Notable conference lectures included the presentation of a predictive model of tumor response in lung cancer based on daily MV-CT imaging. The model may allow determination of effective adaptive radiotherapy strategies early in the course of radiation treatment. New techniques were presented to further reduce treatment time and to decrease the dose outside the planning target volume (''dynamic jaws',' ''dynamic couch''). Treatment protocols were discussed including a study directed from the University Clinic Essen in a method for treating multiple brain metastases with a simultaneous integrated boost technique applying 10x5 Gy within the metastases. This strategy is going to be evaluated against whole-brain radiotherapy with 10 x 3 Gy in a randomized phase II trial. Another interesting concept was the use of tomotherapy to treat the whole abdominal volume for ovarian cancer while sparing liver, kidneys and bone marrow. Tomotherapy proved its feasibility in the treatment of mesothelioma, a clinically challenging disease in which therapy options were previously limited due to complications of organs at risk. Many presentations discussed the application of tomotherapy in complex cases including large-volume lymphoma where avoidance of critical structures may lead to a reduction of long-term late toxicity. Presentations of user groups from both the USA and Europe discussed how these groups have

  17. From bench to clinic and back: Perspective on the 1st IQPC Translational Research conference

    Directory of Open Access Journals (Sweden)

    Hörig Heidi

    2004-12-01

    Full Text Available Abstract Translational Research (TR provides a set of tools and communication context for scientists and clinicians to optimize the drug discovery and development process. In the proceedings of a Princeton conference on this timely topic, the strengths and needs of this developing field were debated. Outcomes and key points from these discussions are summarized in this article which covers the topics of defining what we mean by translational research (both theoretically and in operational terms, ways in which to engender the TR mindset and embed it in organizations such as the pharmaceutical industry in order to optimize the impact of available technologies (including imaging methods, the scientific basis and under-pinnings of TR including genomics knowledge, information sharing, as well as examples of application to drug discovery and development. Importantly, it should be noted that collaborations and communications between the stakeholders in this field, namely academia, industry and regulatory authorities, must be strengthened in order for the promise of TR to be delivered as better therapies to patients.

  18. Clinical skin imaging using color spatial frequency domain imaging (Conference Presentation)

    Science.gov (United States)

    Yang, Bin; Lesicko, John; Moy, Austin J.; Reichenberg, Jason; Tunnell, James W.

    2016-02-01

    Skin diseases are typically associated with underlying biochemical and structural changes compared with normal tissues, which alter the optical properties of the skin lesions, such as tissue absorption and scattering. Although widely used in dermatology clinics, conventional dermatoscopes don't have the ability to selectively image tissue absorption and scattering, which may limit its diagnostic power. Here we report a novel clinical skin imaging technique called color spatial frequency domain imaging (cSFDI) which enhances contrast by rendering color spatial frequency domain (SFD) image at high spatial frequency. Moreover, by tuning spatial frequency, we can obtain both absorption weighted and scattering weighted images. We developed a handheld imaging system specifically for clinical skin imaging. The flexible configuration of the system allows for better access to skin lesions in hard-to-reach regions. A total of 48 lesions from 31 patients were imaged under 470nm, 530nm and 655nm illumination at a spatial frequency of 0.6mm^(-1). The SFD reflectance images at 470nm, 530nm and 655nm were assigned to blue (B), green (G) and red (R) channels to render a color SFD image. Our results indicated that color SFD images at f=0.6mm-1 revealed properties that were not seen in standard color images. Structural features were enhanced and absorption features were reduced, which helped to identify the sources of the contrast. This imaging technique provides additional insights into skin lesions and may better assist clinical diagnosis.

  19. Fast full-field OCT assessment of clinical tissue specimens (Conference Presentation)

    Science.gov (United States)

    Dalimier, Eugénie; Harms, Fabrice; Brossolet, Charles; Benoit, Emilie; Martins, Franck; Boccara, Claude

    2016-03-01

    Full-field optical coherence tomography (FFOCT) offers a non-invasive method of obtaining images of biological tissues at ultrahigh resolution (1µm in all 3 directions) approaching traditional histological sections. Previous clinical studies have shown the high efficiency of this imaging technique for the detection of cancer on various organs. This promises great potential of the technique for an ex-vivo quick analysis of surgical resections or biopsy specimens, in the aim to help the surgeon/radiologist decide on the course of action. Here we will present some of the latest technical developments on a FFOCT system which can produce 1cm2 images with 1 µm resolution in 1 minute. Larger samples, up to 50mm diameter, can also be imaged. Details on the large sample handling, high-speed image acquisition, optimized scanning, and accelerated GPU tiles stitching will be given. Results on the clinical applications for breast, urology, and digestive tissues will also be given. They highlight the relevance of the system characteristics for the detection of cancer on ex-vivo specimens. FFOCT now appears clearly as a very fast and non-destructive imaging technique that provides a quick assessment of the tissue morphology. With the benefit of both new technical developments and clinical validation, it turned into a mature technique to be implemented in the clinical environment. In particular, the technique holds potential for the fast ex-vivo analysis of excision margins or biopsies in the operating room.

  20. Critical dosimetry measures and surrogate tools that can facilitate clinical success in PDT (Conference Presentation)

    Science.gov (United States)

    Pogue, Brian W.; Davis, Scott C.; Kanick, Stephen C.; Maytin, Edward V.; Pereira, Stephen P.; Palanisami, Akilan; Hasan, Tayyaba

    2016-03-01

    Photodynamic therapy can be a highly complex treatment with more than one parameter to control, or in some cases it is easily implemented with little control other than prescribed drug and light values. The role of measured dosimetry as related to clinical adoption has not been as successful as it could have been, and part of this may be from the conflicting goals of advocating for as many measurements as possible for accurate control, versus companies and clinical adopters advocating for as few measurements as possible, to keep it simple. An organized approach to dosimetry selection is required, which shifts from mechanistic measurements in pre-clinical and early phase I trials, towards just those essential dose limiting measurements and a focus on possible surrogate measures in phase II/III trials. This essential and surrogate approach to dosimetry should help successful adoption of clinical PDT if successful. The examples of essential dosimetry points and surrogate dosimetry tools which might be implemented in phase II and higher trials are discussed for solid tissue PDT with verteporfin and skin lesion treatment with aminolevulinc acid.

  1. Creating an optical spectroscopy system for use in a primary care clinical setting (Conference Presentation)

    Science.gov (United States)

    Eshein, Adam; Nguyen, The-Quyen; Radosevich, Andrew J.; Gould, Bradley; Wu, Wenli; Konda, Vani; Yang, Leslie W.; Koons, Ann; Feder, Seth; Valuckaite, Vesta; Roy, Hemant K.; Backman, Vadim

    2016-03-01

    While there are a plethora of in-vivo spectroscopic techniques that have demonstrated the ability to detect a number of diseases in research trials, very few techniques have successfully become a fully realized clinical technology. This is primarily due to the stringent demands on a clinical device for widespread implementation. Some of these demands include: simple operation requiring minimal or no training, safe for in-vivo patient use, no disruption to normal clinic workflow, tracking of system performance, warning for measurement abnormality, and meeting all FDA guidelines for medical use. Previously, our group developed a fiber optic probe-based optical sensing technique known as low-coherence enhanced backscattering spectroscopy (LEBS) to quantify tissue ultrastructure in-vivo. Now we have developed this technique for the application of prescreening patients for colonoscopy in a primary care (PC) clinical setting. To meet the stringent requirements for a viable medical device used in a PC clinical setting, we developed several novel components including an automated calibration tool, optical contact sensor for signal acquisition, and a contamination sensor to identify measurements which have been affected by debris. The end result is a state-of-the-art medical device that can be realistically used by a PC physician to assess a person's risk for harboring colorectal precancerous lesions. The pilot study of this system shows great promise with excellent stability and accuracy in identifying high-risk patients. While this system has been designed and optimized for our specific application, the system and design concepts are universal to most in-vivo fiber optic based spectroscopic techniques.

  2. Adults with genetic syndromes and cardiovascular abnormalities: Clinical history and management

    Science.gov (United States)

    Lin, Angela E.; Basson, Craig T.; Goldmuntz, Elizabeth; Magoulas, Pilar L.; McDermott, Deborah A.; McDonald-McGinn, Donna M.; McPherson, Elspeth; Morris, Colleen A.; Noonan, Jacqueline; Nowak, Catherine; Pierpont, Mary Ella; Pyeritz, Reed E.; Rope, Alan F.; Zackai, Elaine; Pober, Barbara R.

    2009-01-01

    Cardiovascular abnormalities, especially structural congenital heart defects (CHDs), commonly occur in malformation syndromes and genetic disorders. Individuals with syndromes comprise a significant proportion of those affected with selected CHDs such as complete atrioventricular canal, interrupted arch type B, supravalvar aortic stenosis and pulmonary stenosis. As these individuals age, they contribute to the growing population of adults with special health care needs. Although most will require longterm cardiology followup, primary care providers, geneticists and other specialists should be aware of (1) the type and frequency of cardiovascular abnormalities, (2) the range of clinical outcomes, and (3) guidelines for prospective management and treatment of potential complications. This article reviews fundamental genetic, cardiac, medical and reproductive issues associated with common genetic syndromes which are frequently associated with a cardiovascular abnormality. New data are also provided about the cardiac status of adults with a 22q11.2 deletion and with Down syndrome. PMID:18580689

  3. Genetics

    Science.gov (United States)

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  4. An experimental case-conference programme for obstetrics and gynaecology clinical students.

    OpenAIRE

    ten Have, H; Essed, G.

    1989-01-01

    Since the founding of the University of Limburg (1974), in The Netherlands, an innovative medical curriculum has been guided by educational principles of problem-orientation, continuous assessment, student initiative and attitude development. The teaching of medical ethics was built into the preclinical curriculum from the start. However, the clinical years remained largely unaffected, and only recently has an effort been made to extend the educational philosophy to this more or less traditio...

  5. Clinical use of a portable dual microscope system for smartphone (Conference Presentation)

    Science.gov (United States)

    Kurachi, Cristina; Brognara, Gabriel; Gómez-García, Pablo A.; Carbinatto, Fernanda; Silva, Eduardo V.; Lombardi, Wellington; Inada, Natália M.; Bagnato, Vanderlei S.

    2016-03-01

    Cervical cancer is still one of the most relevant women cancer types, since the 5-year survival rate is of only around 68%. Prevention and early diagnosis are the best strategies to improve cervical cancer prognosis. Conventional diagnosis procedure in Gynecology is mainly based on the macroscopic clinical evaluation, Pap smear cytology, and biopsy, if needed. A portable microscope with dual configuration and its use for diagnosis in Gynecology is investigated. The microscope has interchangeable parts that allow its use for cytopathology smear samples or in situ endoscopic tissue interrogation, both using acriflavine as a nuclei marker. Patients of the Women Ambulatory of the School of Medicine (UNIARA, Araraquara, Brazil) were interrogated during the colposcopy examination. The cervix was initially cleaned using an acetic acid solution, and a 0.05% (wt/vol) acriflavine in saline solution was topically applied at the tissue surface using a cotton swab. Microendoscopy images were taken from clinically normal cervix mucosa and from detected lesions. An image processing is performed to evaluate the cell nuclei morphology and the cytoplasm/nuclei ratio. The Pap smear results and the histology analyses are taken as gold standard for the diagnosis. Preliminary results in 5 patients demonstrated the potential use of our microscope at the clinical setting.

  6. Overcoming burdens in the regulation of clinical research in children. Proceedings of a consensus conference, in historical context

    Directory of Open Access Journals (Sweden)

    Levine Robert J

    2011-12-01

    Full Text Available Abstract Background Many investigators are concerned that the modes of implementation and enforcement of the federal regulations designed to protect children are unduly impeding pediatric clinical research. Objective To assess regulatory impediments to clinical research involving children and to develop recommendations to ameliorate them. Participants The Pediatric Endocrine Society and The Endocrine Society convened a consensus conference involving experts and stakeholders in patient-oriented research involving children and adolescents in 2008. Consensus process Following presentations that reviewed problematic issues around key regulations, participants divided into working groups to develop potential solutions that could be adopted at local and federal levels. Presentations to the full assembly were then debated. A writing committee then drafted a summary of the discussions and main conclusions, placing them in historical context, and submitted it to all participants for comment with the aim of developing consensus. Conclusions Recommendations designed to facilitate the ethical conduct of research involving children addressed the interpretation of ambiguous regulatory terms such as "minimal risk" and "condition" and called for the development by professional societies of best practice primers for common research procedures that would be informative to both investigators and institutional review boards. A call was issued for improved guidance from the Office for Human Research Protections and Food and Drug Administration as well as for the development by professional societies of a process to monitor progress in improving human subject research regulation. Finally, a need for systematic research to define the nature and extent of institutional obstacles to pediatric research was recognized.

  7. Fatal familial insomnia: clinical and pathologic heterogeneity in genetic half brothers.

    Science.gov (United States)

    Johnson, M D; Vnencak-Jones, C L; McLean, M J

    1998-12-01

    We describe clinical and pathologic features of a patient with fatal familial insomnia (FFI) whose prion (PrP) genotype is D178N coupled with methionine at codon 129 on his mutant allele and valine at codon 129 on his normal allele. A cousin (genetic half brother) with identical PrP genotypes exhibited strikingly different clinical and pathologic changes. Comparison of these cousins shows the phenotypic heterogeneity of FFI and suggests that the phenotypic expression of D178N is influenced by multiple factors. PMID:9855529

  8. Clinical and genetic investigation of families with type II Waardenburg syndrome

    OpenAIRE

    Chen, Yong; YANG, FUWEI; ZHENG, HEXIN; Zhou, Jianda; ZHU, GANGHUA; HU, PENG; Wu, Weijing

    2016-01-01

    The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia-associated transcription factor (MITF),...

  9. Clinical audit of genetic testing and referral patterns for fragile X and associated conditions.

    Science.gov (United States)

    Cotter, Megan; Archibald, Alison D; McClaren, Belinda J; Burgess, Trent; Francis, David; Hills, Louise; Martyn, Melissa; Oertel, Ralph; Slater, Howard; Cohen, Jonathan; Metcalfe, Sylvia A

    2016-06-01

    An audit was conducted of laboratory/clinical databases of genetic tests performed between January 2003 and December 2009, and for 2014, as well as referrals to the clinical service and a specialist multidisciplinary clinic, to determine genetic testing request patterns for fragile X syndrome and associated conditions and referrals for genetic counseling/multidisciplinary management in Victoria, Australia. An expanded allele (full mutation, premutation or intermediate) was found in 3.7% of tests. Pediatricians requested ∼70% of test samples, although fewer general practitioners and more obstetricians/gynecologists ordered tests in 2014. Median age at testing for individuals with a full mutation seeking a diagnosis without a fragile X family history was 4.3 years (males) and 9.4 years (females); these ages were lower when pediatricians ordered the tests (2.1 years and 6.1 years, respectively). Individuals with a premutation were generally tested at a later age (median age: males, 33.2 years; females, 36.4 years). Logistic regression showed that a family history of ID (OR 3.28 P = 0.005, CI 1.77-5.98) was the only indication to independently increase the likelihood of a test-positive (FM or PM) result. Following testing, ∼25% of full mutation or premutation individuals may not have attended clinical services providing genetic counseling or multidisciplinary management for these families. The apparent delay in fragile X syndrome diagnosis and lack of appropriate referrals for some may result in less than optimal management for these families. These findings suggest continued need for awareness and education of health professionals around diagnosis and familial implications of fragile X syndrome and associated conditions. © 2016 Wiley Periodicals, Inc. PMID:26892444

  10. Erythropoietin in the General Population: Reference Ranges and Clinical, Biochemical and Genetic Correlates

    OpenAIRE

    Niels Grote Beverborg; Niek Verweij; Klip, IJsbrand T.; Haye H van der Wal; Voors, Adriaan A.; van Veldhuisen, Dirk J.; Gansevoort, Ron T.; Bakker, Stephan J. L.; Pim van der Harst; Peter van der Meer

    2015-01-01

    Background Although erythropoietin has been used for decades in the treatment of anemia, data regarding endogenous levels in the general population are scarce. Therefore, we determined erythropoietin reference ranges and its clinical, biochemical and genetic associations in the general population. Methods We used data from 6,777 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Fasting venous blood samples were obtained in the morning from all partic...

  11. Effective feature selection of clinical and genetic to predict warfarin dose using artificial neural network

    OpenAIRE

    Mohammad Karim Sohrabi; Alireza Tajik

    2016-01-01

    Background: Warfarin is one of the most common oral anticoagulant, which role is to prevent the clots. The dose of this medicine is very important because changes can be dangerous for patients. Diagnosis is difficult for physicians because increase and decrease in use of warfarin is so dangerous for patients. Identifying the clinical and genetic features involved in determining dose could be useful to predict using data mining techniques. The aim of this paper is to provide a convenient way t...

  12. Diagnosing Autism in Individuals with Known Genetic Syndromes: Clinical Considerations and Implications for Intervention

    OpenAIRE

    Hepburn, Susan L.; Moody, Eric J.

    2011-01-01

    Assessing symptoms of autism in persons with known genetic syndromes associated with intellectual and/or developmental disability is a complex clinical endeavor. We suggest that a developmental approach to evaluation is essential to reliably teasing apart global impairments from autism-specific symptomology. In this chapter, we discuss our assumptions about autism spectrum disorders, the process of conducting a family-focused, comprehensive evaluation with behaviorally complex children and so...

  13. Retinoma and Phthisis Bulbi of Retinoblastoma 1.Clinical and Genetic Analysis

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    Retinoma and phthisis bulbi of retinoblastoma are rare entitiesfound in retinoblastoma patients and their relatives.Eleven cases of phthisisbulbi of retinoblastoma and 9 cases of retinoma were identified from 1966 to1991 in our center.The clinic data show that retinoma and phthisis bulbi areclosely related to the retinoblastoma gene.Enucleation should be carried outas soon as possible without hesitation for the phthisis of eyes with retinoblas-toma.Genetic counseling and frequent observation should be p...

  14. Host and viral genetic correlates of clinical definitions of HIV-1 disease progression.

    Directory of Open Access Journals (Sweden)

    Concepción Casado

    Full Text Available BACKGROUND: Various patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP elite controllers (LTNP-EC, viremic controllers (LTNP-VC, and viremic non controllers (LTNP-NC, as well as of chronic progressors (P and rapid progressors (RP. METHODOLOGY AND PRINCIPAL FINDINGS: We re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01, HLA-C rs9264942 (p-0.06, and protective CCR5/CCR2 haplotypes (p-0.02 across groups, and the presence of viruses with an ancestral genotype in the "viral dating" (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor support the differences among principal clinical groups of HIV-1 infected individuals. CONCLUSIONS: A combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research.

  15. HIV-1 Genetic Variability in Cuba and Implications for Transmission and Clinical Progression.

    Science.gov (United States)

    Blanco, Madeline; Machado, Liuber Y; Díaz, Héctor; Ruiz, Nancy; Romay, Dania; Silva, Eladio

    2015-10-01

    INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVE Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients' clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and

  16. Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy.

    Science.gov (United States)

    Liu, Xinhong; Wu, Huamin; Gong, Jian; Wang, Tao; Yan, Chuanzhu

    2016-05-01

    The aim of the present study was to report on a family with pathologically and genetically diagnosed autosomal dominant inherited centronuclear myopathy (CNM). In addition, this study aimed to investigate the clinical, pathological and molecular genetic characteristics of the disease. This pedigree was traced back three generations, four patients underwent neurological examination, two patients underwent muscle biopsy, and eight family members were subjected to dynamin 2 (DNM2) gene mutation analysis. DNM2 mutations were detected in seven family members, of which four patients exhibited DNM2 mutation‑specific clinical and pathological features. Lower extremity weakness was the predominant symptom of these patients, however, proximal and distal lower extremity involvement was inconsistent. All patients exhibited marked systematic muscle atrophy and various degrees of facial muscle involvement. The patients presented the typical pathological changes of CNM, and their muscle tissues were heavily replaced by adipose tissue, with clustered distribution of muscle fibers as another notable feature. DNM2‑CNM patients of this pedigree exhibited heterogeneous clinical and pathological features, providing a basis for further molecular genetic analysis. PMID:27035234

  17. The clinical and genetic features of the COPD asthma overlap syndrome

    Science.gov (United States)

    Hardin, Megan; Cho, Michael; McDonald, Merry-Lynn; Beaty, Terri; Ramsdell, Joe; Bhatt, Surya; van Beek, Edwin J. R.; Make, Barry J.; Crapo, James D.; Silverman, Edwin K.; Hersh, Craig P.

    2014-01-01

    Background Individuals with COPD and asthma are an important but poorly characterized group. The genetic determinants of COPD-asthma overlap have not been studied. Objective Identify clinical features and genetic risk factors for COPD-asthma overlap. Methods Subjects were current or former smoking non-Hispanic whites (NHW) or African-Americans (AA) with COPD. Overlap subjects reported a history of physician-diagnosed asthma before the age of 40. We compared clinical and radiographic features between COPD and overlap subjects. We performed genome-wide association studies (GWAS) in the NHW and AA populations, and combined these results in a meta-analysis. Results More women and African Americans reported a history of asthma. Overlap subjects had more severe and more frequent respiratory exacerbations, less emphysema, and greater airway wall thickness compared to subjects with COPD alone. The NHW GWAS identified SNPs in CSMD1 (rs11779254, P=1.57×10−6) and SOX5(rs59569785, P=1.61×10−6) and the meta-analysis identified SNPs in the gene GPR65 (rs6574978, P=1.18×10−7) associated with COPD-asthma overlap. Conclusions Overlap subjects have more exacerbations, less emphysema and more airway disease for any degree of lung function impairment compared to COPD alone. We identified novel genetic variants associated with this syndrome. COPD-asthma overlap is an important syndrome and may require distinct clinical management. PMID:24876173

  18. Genetic Testing as a New Standard for Clinical Diagnosis of Color Vision Deficiencies

    Science.gov (United States)

    Davidoff, Candice; Neitz, Maureen; Neitz, Jay

    2016-01-01

    Purpose The genetics underlying inherited color vision deficiencies is well understood: causative mutations change the copy number or sequence of the long (L), middle (M), or short (S) wavelength sensitive cone opsin genes. This study evaluated the potential of opsin gene analyses for use in clinical diagnosis of color vision defects. Methods We tested 1872 human subjects using direct sequencing of opsin genes and a novel genetic assay that characterizes single nucleotide polymorphisms (SNPs) using the MassArray system. Of the subjects, 1074 also were given standard psychophysical color vision tests for a direct comparison with current clinical methods. Results Protan and deutan deficiencies were classified correctly in all subjects identified by MassArray as having red–green defects. Estimates of defect severity based on SNPs that control photopigment spectral tuning correlated with estimates derived from Nagel anomaloscopy. Conclusions The MassArray assay provides genetic information that can be useful in the diagnosis of inherited color vision deficiency including presence versus absence, type, and severity, and it provides information to patients about the underlying pathobiology of their disease. Translational Relevance The MassArray assay provides a method that directly analyzes the molecular substrates of color vision that could be used in combination with, or as an alternative to current clinical diagnosis of color defects.

  19. First clinical pilot study with intravascular polarization sensitive optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Villiger, Martin; Karanasos, Antonios; Ren, Jian; Lippok, Norman; Shishkov, Milen; Daemen, Joost; Van Mieghem, Nicolas; Diletti, Roberto; Valgimigli, Marco; van Geuns, Robert-Jan; de Jaegere, Peter; Zijlstra, Felix; van Soest, Gijs; Nadkarni, Seemantini; Regar, Evelyn; Bouma, Brett E.

    2016-02-01

    Polarization sensitive (PS) OCT measures the polarization states of the light backscattered by tissue and provides measures of tissue birefringence and depolarization in addition to the structural OCT signal. Ex vivo studies have demonstrated that birefringence is increased in tissue rich in collagen and with elevated smooth muscle cell content. Preliminary data further suggests that depolarization can identify regions of macrophage infiltration, lipid, and irregularly arranged collagen fibers. These are important aspects of the mechanical integrity and vulnerability of atherosclerotic plaques. To evaluate the potential of PS-OCT in the clinical setting, we combined our custom PS-OCT system with commercially available OCT catheters (Fastview, Terumo Corporation) and performed a pilot study in 30 patients, scheduled to undergo percutaneous coronary intervention (PCI) on the grounds of stable or unstable angina. A total of 82 pullbacks in 39 vessels were performed, either in the native coronary arteries or post procedure. Comparing consecutive pullbacks of the same coronary artery, we found excellent agreement between the polarization features in the repeat pullbacks, validating the repeatability and robustness of PS-OCT in the clinical in vivo setting. In addition we observed that the birefringence and depolarization features vary significantly across lesions with identical structural OCT appearance, suggesting morphological subtypes. This first human pilot study proved the feasibility and robustness of intravascular PS-OCT. PS-OCT achieves improved tissue characterization and may help in identifying high-risk plaques, with the potential to ultimately improve risk stratification and help guiding PCI.

  20. Genetic variant in CD44 confer susceptibility to acute skin reaction in breast cancer patients undergoing radiotherapy

    International Nuclear Information System (INIS)

    Heterogeneity in toxicity to normal tissue is observed in 10% of cancer patients after radiotherapy (RT) which limits the therapeutic outcome. Response to RT is manifested from alterations in gene of vivid pathways involving DNA damage-repair, inflammatory cytokine, cell cycle regulation, antioxidant response etc. Therefore, the common sequence variants in these radioresponsive genes may modify the severity of normal tissue toxicity and identification of the same may have clinical relevance as a predictive biomarker. The present study was aimed to evaluate the potential modifying role of genetic variants in NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, LIG3, SH3GL1, BAXS, XRCC1, MAD2L2 and TGFBR3 on the individual susceptibility to RT induced acute skin reactions. All the 132 breast cancer patients were treated with a total dose of 50 Gy in case of mastectomy and 60 Gy in breast conservation surgery. The severity of skin damage was scored according to the Radiation Therapy Oncology Group (RTOG) criteria and the toxicity scores were dichotomized as non-over-responders (NOR; RTOG<2) and over-responders (NOR;RTOG>2) for analysis. Out of the 132 subjects, 44 were ORs. Among the 20 studied SNPs of indicated genes, the rs8193 (CD44) polymorphism lying in the miRNA binding site was significantly (p<0.05) associated with the RT induced adverse skin reactions. The non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed. Therefore, though the role of CD44 in radiosensitivity is unknown, the change in the miRNA binding to CD44mRNA transcripts may regulate expression of several genes involved in pathophysiology of normal tissue radiosensitivity leading to the observed outcome. (author)

  1. DNA sequencing conference, 2

    Energy Technology Data Exchange (ETDEWEB)

    Cook-Deegan, R.M. [Georgetown Univ., Kennedy Inst. of Ethics, Washington, DC (United States); Venter, J.C. [National Inst. of Neurological Disorders and Strokes, Bethesda, MD (United States); Gilbert, W. [Harvard Univ., Cambridge, MA (United States); Mulligan, J. [Stanford Univ., CA (United States); Mansfield, B.K. [Oak Ridge National Lab., TN (United States)

    1991-06-19

    This conference focused on DNA sequencing, genetic linkage mapping, physical mapping, informatics and bioethics. Several were used to study this sequencing and mapping. This article also discusses computer hardware and software aiding in the mapping of genes.

  2. Corneal tissue water content mapping with THz imaging: preliminary clinical results (Conference Presentation)

    Science.gov (United States)

    Sung, Shijun; Bajwa, Neha; Deng, Sophie X.; Taylor, Zachary; Grundfest, Warren

    2016-03-01

    Well-regulated corneal water content is critical for ocular health and function and can be adversely affected by a number of diseases and injuries. Current clinical practice limits detection of unhealthy corneal water content levels to central corneal thickness measurements performed by ultrasound or optical coherence tomography. Trends revealing increasing or decreasing corneal thickness are fair indicators of corneal water content by individual measurements are highly inaccurate due to the poorly understood relationship between corneal thickness and natural physiologic variation. Recently the utility of THz imaging to accuarately measure corneal water content has been explored on with rabbit models. Preliminary experiments revealed that contact with dielectric windows confounded imaging data and made it nearly impossible to deconvolve thickness variations due to contact from thickness variations due to water content variation. A follow up study with a new optical design allowed the acquisition of rabbit data and the results suggest that the observed, time varying contrast was due entirely to the water dynamics of the cornea. This paper presents the first ever in vivo images of human cornea. Five volunteers with healthy cornea were recruited and their eyes were imaged three times over the course of a few minutes with our novel imaging system. Noticeable changes in corneal reflectivity were observed and attributed to the drying of the tear film. The results suggest that clinically compatible, non-contact corneal imaging is feasible and indicate that signal acquired from non-contact imaging of the cornea is a complicated coupling of stromal water content and tear film.

  3. Diagnostic outcome following routine genetics clinic referral for the assessment of global developmental delay.

    LENUS (Irish Health Repository)

    Shahdadpuri, R

    2012-02-01

    The aim of this study was to ascertain the diagnostic yield following a routine genetics clinic referral for the assessment of global developmental delay. Detailed retrospective review of 119 complete consecutive case notes of patients referred to one single clinical geneticist over a 14 month time period was undertaken (n = 119; 54 males, 65 females). The age at initial review ranged from 2 months to 37 years 3 months (mean 8 y 3 mo [SD 7 y 10 mo]). We made a diagnosis in 36\\/119 (30%); 21\\/36 were new diagnoses and 15\\/36 were confirmations of diagnoses. We removed a wrong diagnostic label in 8\\/119 (7%). In 3\\/8 we were able to achieve a diagnosis but in 5\\/8 no alternative diagnosis was reached. We had a better diagnostic rate where the patients were dysmorphic (odds ratio [OR] 1.825; 95% confidence interval [CI] 1.065 to 3.128, p = 0.044). In the majority, the diagnosis was made by clinical examination only. Molecular diagnosis was reached in seven cases. Five cases were confirmed by cytogenetic analysis. Brain magnetic resonance imaging (MRI) revealed a diagnosis in three cases. This study confirms the importance of a clinical genetics assessment in the investigation of global developmental delay.

  4. Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates.

    Science.gov (United States)

    Courbet, Alexis; Endy, Drew; Renard, Eric; Molina, Franck; Bonnet, Jérôme

    2015-05-27

    Whole-cell biosensors have several advantages for the detection of biological substances and have proven to be useful analytical tools. However, several hurdles have limited whole-cell biosensor application in the clinic, primarily their unreliable operation in complex media and low signal-to-noise ratio. We report that bacterial biosensors with genetically encoded digital amplifying genetic switches can detect clinically relevant biomarkers in human urine and serum. These bactosensors perform signal digitization and amplification, multiplexed signal processing with the use of Boolean logic gates, and data storage. In addition, we provide a framework with which to quantify whole-cell biosensor robustness in clinical samples together with a method for easily reprogramming the sensor module for distinct medical detection agendas. Last, we demonstrate that bactosensors can be used to detect pathological glycosuria in urine from diabetic patients. These next-generation whole-cell biosensors with improved computing and amplification capacity could meet clinical requirements and should enable new approaches for medical diagnosis. PMID:26019219

  5. Molecular genetic characterisation of the Asc locus of tomato conferring resistance to the fungal pathogen Alternaria alternata f. sp. lycopersici

    NARCIS (Netherlands)

    Biezen, E.A. van der; Overduin, B.; Kneppers, T.J.A.; Mesbah, L.A.; Nijkamp, H.J.J.; Hille, J.

    1994-01-01

    The Alternaria stem canker disease of tomato is caused by the fungal pathogen Alternaria alternata f. sp. lycopersici and its host-selective AAL-toxins. Resistance to the pathogen and insensitivity to the toxins are conferred by the Asc locus on chromosome 3L. Sensitivity to AAL-toxins is a relative

  6. SIGEF Conference

    CERN Document Server

    Terceño-Gómez, Antonio; Ferrer-Comalat, Joan; Merigó-Lindahl, José; Linares-Mustarós, Salvador

    2015-01-01

    This book is a collection of selected papers presented at the SIGEF conference, held at the Faculty of Economics and Business of the University of Girona (Spain), 06-08 July, 2015. This edition of the conference has been presented with the slogan “Scientific methods for the treatment of uncertainty in social sciences”. There are different ways for dealing with uncertainty in management. The book focuses on soft computing theories and their role in assessing uncertainty in a complex world. It gives a comprehensive overview of quantitative management topics and discusses some of the most recent developments in all the areas of business and management in soft computing including Decision Making, Expert Systems and Forgotten Effects Theory, Forecasting Models, Fuzzy Logic and Fuzzy Sets, Modelling and Simulation Techniques, Neural Networks and Genetic Algorithms and Optimization and Control. The book might be of great interest for anyone working in the area of management and business economics and might be es...

  7. EURECCA consensus conference highlights about rectal cancer clinical management: The radiation oncologist’s expert review

    International Nuclear Information System (INIS)

    Background and Purpose: Although rectal and colon cancer management has progressed greatly in the last few decades clinical outcomes still need to be optimized. Furthermore, consensus is required on several issues as some of the main international guidelines provide different recommendations. The European Registration of Cancer Care (EURECCA) drew up documents to standardize management and care in Europe and aid in decision-making. Material and Methods: In the present section the panel of experts reviews and discusses data from the literature on rectal cancer, focusing on recommendations for selecting between short-course radiotherapy (SCRT) and long-course radio-chemotherapy (LCRTCT) as preoperative treatment as well as on the controversies about adjuvant treatment in patients who had received a pre-operative treatment. Results: The starting-point of the present EURECCA document is that adding SCRT or LCRTCT to TME improved loco-regional control but did not increase overall survival in any single trial which, in any case, had improved with the introduction of total mesorectal excision (TME) into clinical practice. Moderate consensus was achieved for cT3 anyNM0 disease. In this frame, agreement was reached on either SCRT followed by immediate surgery or LCRTCT with delayed surgery for mesorectal fascia (MRF) negative tumors at presentation. LCRTCT was recommended for tumor shrinkage in MRF+ at presentations but if patients were not candidates for chemotherapy, SCRT with delayed surgery is an option/alternative. LCRTCT was recommended for cT4 anycNM0. SCRT offers the advantages of less acute toxicity and lower costs, and LCRTCT tumor shrinkage and down-staging, with 13–36% pathological complete response (pCR) rates. To improve the efficacy of preoperative treatment both SCRT and LCRTCT have been, or are being, associated with diverse schedules of chemotherapy and even new targeted therapies but without any definitive evidence of benefit. Nowadays, standard

  8. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management.

    Science.gov (United States)

    Gammon, Amanda; Jasperson, Kory; Champine, Marjan

    2016-01-01

    Cowden syndrome (CS) is an often difficult to recognize hereditary cancer predisposition syndrome caused by mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN). In addition to conferring increased cancer risks, CS also predisposes individuals to developing hamartomatous growths in many areas of the body. Due to the rarity of CS, estimates vary on the penetrance of certain phenotypic features, such as macrocephaly and skin findings (trichilemmomas, mucocutaneous papules), as well as the conferred lifetime cancer risks. To address this variability, separate clinical diagnostic criteria and PTEN testing guidelines have been created to assist clinicians in the diagnosis of CS. As knowledge of CS increases, making larger studies of affected patients possible, these criteria continue to be refined. Similarly, the management guidelines for cancer screening and risk reduction in patients with CS continue to be updated. This review will summarize the current literature on CS to assist clinicians in staying abreast of recent advances in CS knowledge, diagnostic approaches, and management. PMID:27471403

  9. Preimplantation genetic diagnosis for mitochondrial DNA disorders: ethical guidance for clinical practice.

    Science.gov (United States)

    Bredenoord, Annelien; Dondorp, Wybo; Pennings, Guido; de Die-Smulders, Christine; Smeets, Bert; de Wert, Guido

    2009-12-01

    Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial DNA (mtDNA) disorders raises several ethical questions in clinical practice. This paper discusses the major conditions for good clinical practice. Our starting point is that PGD for mtDNA mutations should as far as possible be embedded in a scientific research protocol. For every clinical application of PGD for mtDNA disorders, it is not only important to avoid a 'high risk of serious harm' to the future child, but also to consider to what extent it would be possible, desirable and proportional to try to reduce the health risks and minimize harm. The first issue we discuss is oocyte sampling, which may point out whether PGD is feasible for a specific couple. The second issue is whether one blastomere represents the genetic composition of the embryo as a whole -- and how this could (or should) be investigated. The third issue regards the cutoff points below which embryos are considered to be eligible for transfer. We scrutinize how to determine these cutoff points and how to use these cutoff points in clinical practice -- for example, when parents ask to take more or less risks. The fourth issue regards the number of cycles that can (or should) justifiably be carried out to find the best possible embryo. Fifth, we discuss whether follow-up studies should be conducted, particularly the genetic testing of children born after IVF/PGD. Finally, we offer the main information that is required to obtain a truly informed consent. PMID:19471315

  10. Shared Genetic Influences Between Attention-Deficit/Hyperactivity Disorder (ADHD) Traits in Children and Clinical ADHD

    Science.gov (United States)

    Stergiakouli, Evie; Martin, Joanna; Hamshere, Marian L.; Langley, Kate; Evans, David M.; St Pourcain, Beate; Timpson, Nicholas J.; Owen, Michael J.; O'Donovan, Michael; Thapar, Anita; Davey Smith, George

    2015-01-01

    Objective Twin studies and genome-wide complex trait analysis (GCTA) are not in agreement regarding heritability estimates for behavioral traits in children from the general population. This has sparked a debate on the possible difference in genetic architecture between behavioral traits and psychiatric disorders. In this study, we test whether polygenic risk scores associated with variation in attention-deficit/hyperactivity disorder (ADHD) trait levels in children from the general population predict ADHD diagnostic status and severity in an independent clinical sample. Method Single nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of ADHD traits in 4,546 children (mean age, 7 years 7 months) from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis (independent clinical sample) and 5,081 control participants. Polygenic scores were tested for association with case-control status and severity of disorder in the clinical sample. Results Increased polygenic score for ADHD traits predicted ADHD case-control status (odds ratio = 1.17 [95% CI = 1.08–1.28], p = .0003), higher ADHD symptom severity (β = 0.29 [95% CI = 0.04–0.54], p = 0.02), and symptom domain severity in the clinical sample. Conclusion This study highlights the relevance of additive genetic variance in ADHD, and provides evidence that shared genetic factors contribute to both behavioral traits in the general population and psychiatric disorders at least in the case of ADHD. PMID:25791149

  11. Genetic Risk Assessment for Women with Epithelial Ovarian Cancer: Referral Patterns and Outcomes in a University Gynecologic Oncology Clinic

    OpenAIRE

    Petzel, Sue v.; Vogel, Rachel Isaksson; Bensend, Tracy; Leininger, Anna; Argenta, Peter A.; Geller, Melissa A.

    2013-01-01

    Little is known about genetic service utilization and ovarian cancer. We identified the frequency and outcome of genetic counseling referral, predictors of referral, and referral uptake for ovarian cancer patients. Using pathology reports, we identified all epithelial ovarian cancer patients seen in a university gynecologic oncology clinic (1/04–8/06). Electronic medical records (EMR) were used to document genetic service referral, time from diagnosis-to-referral, point-in-treatment at referr...

  12. Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk?

    OpenAIRE

    Amiet, Claire; Gourfinkel-An, Isabelle; Laurent, Claudine; Bodeau, Nicolas; Génin, Bérengère; Leguern, Eric; Tordjman, Sylvie; Cohen, David

    2013-01-01

    BACKGROUND: Autism spectrum disorders (ASD) and epilepsy frequently occur together. Prevalence rates are variable, and have been attributed to age, gender, comorbidity, subtype of pervasive developmental disorder (PDD) and risk factors. Recent studies have suggested disparate clinical and genetic settings depending on simplex or multiplex autism. The aim of this study was to assess: 1) the prevalence of epilepsy in multiplex autism and its association with genetic and non-genetic risk factors...

  13. Frequency of CFTR, SPINK1, and Cathepsin B Gene Mutation in North Indian Population: Connections between Genetics and Clinical Data

    OpenAIRE

    Shweta Singh; Gourdas Choudhuri; Sarita Agarwal

    2014-01-01

    Objectives. Genetic mutations and polymorphisms have been correlated with chronic pancreatitis (CP). This study aims to investigate the association of genetic variants of cystic fibrosis transmembrane conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1) genes and Cathepsin B gene polymorphisms with CP and to associate genetic backgrounds with clinical phenotypes. Methods. 150 CP patients and 150 normal controls were enrolled consecutively. We analyzed SPINK-1 N34S...

  14. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.

    Science.gov (United States)

    Robson, Mark E; Bradbury, Angela R; Arun, Banu; Domchek, Susan M; Ford, James M; Hampel, Heather L; Lipkin, Stephen M; Syngal, Sapna; Wollins, Dana S; Lindor, Noralane M

    2015-11-01

    The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services. PMID:26324357

  15. Arrhythmogenic right-ventricular cardiomyopathy: molecular genetics into clinical practice in the era of next generation sequencing.

    Science.gov (United States)

    Poloni, Giulia; De Bortoli, Marzia; Calore, Martina; Rampazzo, Alessandra; Lorenzon, Alessandra

    2016-06-01

    Sudden death, ventricular arrhythmia and heart failure are common features in arrhythmogenic right-ventricular cardiomyopathy (ARVC), an inheritable heart muscle disease, characterized by clinical and genetic heterogeneity. So far, 13 disease genes have been identified, responsible for around 60% of all ARVC cases. In this review, we summarize the main clinical and pathological aspects of ARVC, focusing on the importance of the genetic testing and the application of the new sequencing techniques referred to next generation sequencing technology. PMID:26990921

  16. Genetic diagnosis in clinical psychiatry: A case report of a woman with a 47, XXX karyotype and Fragile X syndrome

    OpenAIRE

    Vandersteen, Anthony M.; David Moore; Celia Donaghue; Neil MacFarlane; Dragana Josifova

    2009-01-01

    Background and Objectives: A recent report highlighted the importance of considering a chromosomal abnormality in the differential diagnosis of adult clinical psychiatry. This case report illustrates the importance of considering Fragile X syndrome, an X-linked genetic disorder associated with psychiatric morbidities. Methods: A 45 years old woman was referred to the clinical genetics department by her psychiatrist for investigation of her gross obesity, hyperphagia, learning difficulties and...

  17. The use of neurophysiological endophenotypes to understand the genetic basis of schizophrenia

    OpenAIRE

    Braff, David L.; Light, Gregory A.

    2005-01-01

    Specifying the complex genetic architecture of the “fuzzy” clinical phenotype of schizophrenia is an imposing problem. Utilizing metabolic, neurocognitive, and neurophysiological “intermediate” endophenotypic measures offers significant advantages from a statistical genetics stand-point. Endophenotypic measures are amenable to quantitative genetic analyses, conferring upon them a major methodological advantage compared with largely qualitative diagnoses using the Diagnostic and Statistical Ma...

  18. Clinical Findings and Genetic Expression Profiling of Three Pigmented Lesions of the Optic Nerve

    Directory of Open Access Journals (Sweden)

    Manuel A. de Alba

    2015-01-01

    Full Text Available Background. Optic disk melanocytoma is a primary tumor of the optic disk that represents a clinical diagnostic challenge due to its similarities with melanoma. Purpose. The authors present three cases in which genetic expression profiling was used to identify tumor prognosis of optic disk melanocytoma. Case Series. In two cases fine-needle aspiration biopsy was performed to obtain tissue through a transvitreal route into the apex of the tumor while the patient underwent pars plana vitrectomy, laser ablation, phacoemulsification with posterior chamber intraocular lens implantation, and intravitreal triamcinolone acetonide. In the other case the tissue was obtained after definite enucleation. Conclusion. Genetic expression profiling is a useful diagnostic tool for classification and can provide vital information to the ocular oncologist regarding prognosis.

  19. Associated syndromes and other genetic variations at a South African cleft lip and palate clinic

    Directory of Open Access Journals (Sweden)

    H.J.S. van den Berg

    2009-09-01

    Full Text Available A retrospective study was done of data on all patients registered at one of the largest cleft lip and palate clinics in South Africa (n = 3174. The associated syndromes and other genetic variations [(abbreviation: ASGV] found in the population of persons suffering from facial cleft deformities (FCD were analysed. 832 (26.2% cleft lip and/ or palate patients presented with ASGV. Fifty-seven different types of syndromes were recorded of which the Fairbaim-Robin appearance (FRA (or Pierre Robin sequence 169 (5.3%, the Demarque-van der Woude syndrome 40 (1.3%, and the holoprosencephaly sequence cases 32 (1.0% were the three most common ones. The three most common genetic variations found in the non-syndromic patients, were heart involvement 53(1.7%, club foot 42 (1.3% and various eye problems 39 (1.2%. The main facial cleft deformity, namely the cleft lip, alveolus and palate (CLAP, was found in 26.2% of the ASGV-group. This particular cleft deformity was recorded at 39.7% in the FCD clinic. On the other hand, the hard and soft palate cleft (hPsP group was found in 32.9% of patients who also had ASGV; in the total group of patients registered at the clinic, it accounted for only 16.6%. This means that ASGV occur less commonly in the CLAP group of patients, than in the hPsP group of patients.

  20. The clinical and genetic features of COPD-asthma overlap syndrome.

    Science.gov (United States)

    Hardin, Megan; Cho, Michael; McDonald, Merry-Lynn; Beaty, Terri; Ramsdell, Joe; Bhatt, Surya; van Beek, Edwin J R; Make, Barry J; Crapo, James D; Silverman, Edwin K; Hersh, Craig P

    2014-08-01

    Individuals with chronic obstructive pulmonary disease (COPD) and asthma are an important but poorly characterised group. The genetic determinants of COPD and asthma overlap have not been studied. The aim of this study was to identify clinical features and genetic risk factors for COPD and asthma overlap. Subjects were current or former smoking non-Hispanic whites or African-Americans with COPD. Overlap subjects reported a history of physician-diagnosed asthma before the age of 40 years. We compared clinical and radiographic features between COPD and overlap subjects. We performed genome-wide association studies (GWAS) in the non-Hispanic whites and African-American populations, and combined these results in a meta-analysis. More females and African-Americans reported a history of asthma. Overlap subjects had more severe and more frequent respiratory exacerbations, less emphysema and greater airway wall thickness compared to subjects with COPD alone. The non-Hispanic white GWAS identified single nucleotide polymorphisms in the genes CSMD1 (rs11779254, p=1.57 × 10(-6)) and SOX5 (rs59569785, p=1.61 × 10(-6)) and the meta-analysis identified single nucleotide polymorphisms in the gene GPR65 (rs6574978, p=1.18 × 10(-7)) associated with COPD and asthma overlap. Overlap subjects have more exacerbations, less emphysema and more airway disease for any degree of lung function impairment compared to COPD alone. We identified novel genetic variants associated with this syndrome. COPD and asthma overlap is an important syndrome and may require distinct clinical management. PMID:24876173

  1. Clinical and genetic factors associated with suicide in mood disorder patients.

    Science.gov (United States)

    Antypa, Niki; Souery, Daniel; Tomasini, Mario; Albani, Diego; Fusco, Federica; Mendlewicz, Julien; Serretti, Alessandro

    2016-03-01

    Suicidality is a continuum ranging from ideation to attempted and completed suicide, with a complex etiology involving both genetic heritability and environmental factors. The majority of suicide events occur in the context of psychiatric conditions, preeminently major depression and bipolar disorder. The present study investigates clinical factors associated with suicide in a sample of 553 mood disorder patients, recruited within the 'Psy Pluriel' center, Centre Européen de Psychologie Médicale, and the Department of Psychiatry of Erasme Hospital (Brussels). Furthermore, genetic association analyses examining polymorphisms within COMT, BDNF, MAPK1 and CREB1 genes were performed in a subsample of 259 bipolar patients. The presence or absence of a previous suicide attempt and of current suicide risk were assessed. A positive association with suicide attempt was reported for younger patients, females, lower educated, smokers, those with higher scores on depressive symptoms and higher functional disability and those with anxiety comorbidity and familial history of suicidality in first- and second-degree relatives. Anxiety disorder comorbidity was the stronger predictor of current suicide risk. No associations were found with polymorphisms within COMT and BDNF genes, whereas significant associations were found with variations in rs13515 (MAPK1) and rs6740584 (CREB1) polymorphisms. From a clinical perspective, our study proposes several clinical characteristics, such as increased depressive symptomatology, anxiety comorbidity, functional disability and family history of suicidality, as correlates associated with suicide. Genetic risk variants in MAPK1 and CREB1 genes might be involved in a dysregulation of inflammatory and neuroplasticity pathways and are worthy of future investigation. PMID:26626456

  2. Clinical implementation of genetic testing in medicine: a US regulatory science perspective.

    Science.gov (United States)

    Lesko, Lawrence J; Schmidt, Stephan

    2014-04-01

    Heterogeneity of treatment effects in unselected patient populations has stimulated various strategic approaches to reduce variability and uncertainty and improve individualization of drug selection and dosing. The rapid growth of DNA sequencing and related technologies has ramped up progress in interpreting germline and somatic mutations and has begun to reshape medicine, especially in oncology. Over the past decade, regulatory agencies realized that they needed to be proactive and not reactive if personalized medicine was to become a reality. The US Food and Drug Administration, in particular, took steps to nurture the field through peer-reviewed publications, co-sponsoring public workshops and issuing guidance for industry. The following two major approaches to personalized medicine were taken: (i) encouragement of de novo co-development of drug-genetic test combinations by industry; and (ii) retrospective assessment of legacy genetic data for the purpose of updating drug labels. The former strategy has been more successful in getting new targeted therapies to the marketplace with successful adoption, while the latter, as evidenced by the low adoption rate of pharmacogenetic testing, has been less successful. This reflection piece makes clear that several important things need to happen to make personalized medicine diffuse in more geographical areas and among more therapeutic specialties. The debate over clinical utility of genetic tests needs to be resolved with consensus on evidentiary standards. Physicians, as gatekeepers of prescription medicines, need to increase their knowledge of genetics and the application of the information to patient care. An infrastructure needs to be developed to make access to genetic tests and decision-support tools available to primary practitioners and specialists outside major medical centres and metropolitan areas. PMID:24286486

  3. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload

    OpenAIRE

    Porto, G.; CARDOSO, C.S.; Gordeuk, V; Cruz, E.; Fraga, J.; Areias, J; Oliveira, J. C.; Bravo, F. (Federico); GANGAIDZO, I.T.; MACPHAIL, A.P.; GOMO, Z.A.; MOYO, V.M.; Melo, G.; Silva, C.; JUSTICA, B.

    2001-01-01

    Eur J Haematol. 2001 Aug;67(2):110-8. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload. Porto G, Cardoso CS, Gordeuk V, Cruz E, Fraga J, Areias J, Oliveira JC, Bravo F, Gangaidzo IT, MacPhail AP, Gomo ZA, Moyo VM, Melo G, Silva C, Justiça B, de Sousa M. Haematology, Santo António General Hospital, Porto, Portugal. Abstract To identify a new marker of expression of diseas...

  4. Genetic analysis of clinical mastitis data for Holstein cattle in the Czech Republic

    OpenAIRE

    L. Zavadilová; Štípková, M.; Šebková, N.; Svitáková, A.

    2015-01-01

    Cases of mastitis were recorded from 22 812 lactations of 10 294 cows on seven farms in the Czech Republic from 2000 to 2012. The per cow number of clinical mastitis (CM) cases per lactation (CM1), number of days of CM per lactation (CM2), and CM considered as an all-or-none trait (CM3) with values of 0 (no CM case) or 1 (at least 1 CM case) were analyzed with linear animal models. Bivariate linear animal models were used for estimation of genetic correlations between CM tra...

  5. A review of advanced genetic testing for clinical prognostication in uveal melanoma.

    Science.gov (United States)

    Werdich, Xiang Q; Jakobiec, Frederick A; Singh, Arun D; Kim, Ivana K

    2013-01-01

    Uveal melanoma (UM) has a strong propensity to metastasize and the prognosis for metastatic disease is very poor. It has been suggested that occult micrometastases are already present, but undetectable, in many patients at the time when the primary ocular tumor is diagnosed and treated. To identify high-risk patients for close monitoring and early intervention with prophylactic adjuvant systemic therapy, an accurate predictive system is necessary for stratifying those patients at risk of developing metastatic disease. To date, many clinical and histopathological features, molecular pathway characteristics, and genetic fingerprints of UM have been suggested for disease prognostication. Among the newest of them, tumor genetics has received the most attention in demonstrating promise as a prognostic tool. Because of the plethora of recent developments, we summarize and compare in this review the important standard and more advanced cytogenetic prognostic markers. We further describe the variety of genetic tests available for prognostication of UM, and provide a critical assessment of the respective advantages and disadvantages of these tools. PMID:24010756

  6. Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss.

    Science.gov (United States)

    Sloan-Heggen, Christina M; Bierer, Amanda O; Shearer, A Eliot; Kolbe, Diana L; Nishimura, Carla J; Frees, Kathy L; Ephraim, Sean S; Shibata, Seiji B; Booth, Kevin T; Campbell, Colleen A; Ranum, Paul T; Weaver, Amy E; Black-Ziegelbein, E Ann; Wang, Donghong; Azaiez, Hela; Smith, Richard J H

    2016-04-01

    Hearing loss is the most common sensory deficit in humans, affecting 1 in 500 newborns. Due to its genetic heterogeneity, comprehensive diagnostic testing has not previously been completed in a large multiethnic cohort. To determine the aggregate contribution inheritance makes to non-syndromic hearing loss, we performed comprehensive clinical genetic testing with targeted genomic enrichment and massively parallel sequencing on 1119 sequentially accrued patients. No patient was excluded based on phenotype, inheritance or previous testing. Testing resulted in identification of the underlying genetic cause for hearing loss in 440 patients (39 %). Pathogenic variants were found in 49 genes and included missense variants (49 %), large copy number changes (18 %), small insertions and deletions (18 %), nonsense variants (8 %), splice-site alterations (6 %), and promoter variants (history of hearing loss or when the loss was congenital and symmetric. The spectrum of implicated genes showed wide ethnic variability. These findings support the more efficient utilization of medical resources through the development of evidence-based algorithms for the diagnosis of hearing loss. PMID:26969326

  7. Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making.

    Science.gov (United States)

    Thouvenot, Pierre; Ben Yamin, Barbara; Fourrière, Lou; Lescure, Aurianne; Boudier, Thomas; Del Nery, Elaine; Chauchereau, Anne; Goldgar, David E; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Nicolas, Alain; Millot, Gaël A

    2016-06-01

    Understanding the medical effect of an ever-growing number of human variants detected is a long term challenge in genetic counseling. Functional assays, based on in vitro or in vivo evaluations of the variant effects, provide essential information, but they require robust statistical validation, as well as adapted outputs, to be implemented in the clinical decision-making process. Here, we assessed 25 pathogenic and 15 neutral missense variants of the BRCA1 breast/ovarian cancer susceptibility gene in four BRCA1 functional assays. Next, we developed a novel approach that refines the variant ranking in these functional assays. Lastly, we developed a computational system that provides a probabilistic classification of variants, adapted to clinical interpretation. Using this system, the best functional assay exhibits a variant classification accuracy estimated at 93%. Additional theoretical simulations highlight the benefit of this ready-to-use system in the classification of variants after functional assessment, which should facilitate the consideration of functional evidences in the decision-making process after genetic testing. Finally, we demonstrate the versatility of the system with the classification of siRNAs tested for human cell growth inhibition in high throughput screening. PMID:27272900

  8. Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making.

    Directory of Open Access Journals (Sweden)

    Pierre Thouvenot

    2016-06-01

    Full Text Available Understanding the medical effect of an ever-growing number of human variants detected is a long term challenge in genetic counseling. Functional assays, based on in vitro or in vivo evaluations of the variant effects, provide essential information, but they require robust statistical validation, as well as adapted outputs, to be implemented in the clinical decision-making process. Here, we assessed 25 pathogenic and 15 neutral missense variants of the BRCA1 breast/ovarian cancer susceptibility gene in four BRCA1 functional assays. Next, we developed a novel approach that refines the variant ranking in these functional assays. Lastly, we developed a computational system that provides a probabilistic classification of variants, adapted to clinical interpretation. Using this system, the best functional assay exhibits a variant classification accuracy estimated at 93%. Additional theoretical simulations highlight the benefit of this ready-to-use system in the classification of variants after functional assessment, which should facilitate the consideration of functional evidences in the decision-making process after genetic testing. Finally, we demonstrate the versatility of the system with the classification of siRNAs tested for human cell growth inhibition in high throughput screening.

  9. Colorectal adenomatous polyposis syndromes: Genetic determinism, clinical presentation and recommendations for care.

    Science.gov (United States)

    Buecher, Bruno

    2016-02-01

    Colorectal adenomatous polyposis constitutes a diverse group of disorders with different modes of inheritance. Molecular diagnosis of this condition has become more complex. In fact, somatic mosaicism for APC mutations now appears to be more frequent than previously thought and rare germline alterations of this gene may be implicated in patients tested negative for "classical" APC mutations (point mutations and large genomic rearrangements). Moreover, the knowledge concerning several aspects of the MUTYH-associated polyposis has improved since its first description in 2002 and germline mutations in new genes have recently been implicated in some cases of unexplained adenomatous polyposis. Genetic testing in probands and their relatives should be conducted in the context of pre- and post-test genetic counseling. The recent advent of New Generation Sequencing (NGS) techniques affords the opportunity to rapidly screen patients for a comprehensive panel of colorectal cancer susceptibility genes in a cost-effective fashion. This type of approach will probably replace the classical sequential approach based on clinical presumptive diagnoses in the near future. The risk of colorectal cancer is very high in affected patients in the absence of appropriate care. Clinical management is complex and should be provided in centers with special expertise in these diseases. This review focuses on the various colorectal adenomatous polyposis syndromes with special attention to more innovative and important aspects. PMID:26805944

  10. Clinical and Genetic Aspects of Sporadic Non-Medullar Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    U Rumjanzeva

    2006-03-01

    Full Text Available The role of somatic mutations in sporadic thyroid cancer is unclear today. Probably they coming out as aetiological factors in carcinogenesis as well as, respectfully to many authors, can to participate in TC pathogenesis and to determine the clinical course and prognosis of the disease. For today as main oncogenes taking part in initiation of thyroid malignant tumors are considered: RET/PTC, TRK, PTEN, P53, RAS, MET, PPARγ. By means of genetic investigations scientists are trying to solve problems with thyroid cancer differentiated diagnostics (cytokeratin-19, cytokeratin-20, mesothelial cells antigen (Hector Battifora MEsotelial (cell or HBME-1, loss of heterozigitoty (LOH in short arm of 3 chromosome (gene VHL -von Hippel Lindau, 3р26. Recently in foreign literature appeared reports of activated mutations in gene BRAF which most frequently are occurred in melanoma and papillary TC. Prognosis of thyroid cancer may reflected by the LOH as a biological breakage as well as changes of tumor suppressive gene P53 which fraught with decrease of disease prognosis. Thus, both researchers and clinicians have many questions concerning the role of genome, particularly in order to precise of genetic abnormality influence on tumor growth and therefore for assessment of clinical prognosis and with aim to chose adequate treatment tactic in each case.

  11. Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making

    Science.gov (United States)

    Thouvenot, Pierre; Ben Yamin, Barbara; Fourrière, Lou; Lescure, Aurianne; Boudier, Thomas; Del Nery, Elaine; Chauchereau, Anne; Goldgar, David E.; Stoppa-Lyonnet, Dominique; Nicolas, Alain; Millot, Gaël A.

    2016-01-01

    Understanding the medical effect of an ever-growing number of human variants detected is a long term challenge in genetic counseling. Functional assays, based on in vitro or in vivo evaluations of the variant effects, provide essential information, but they require robust statistical validation, as well as adapted outputs, to be implemented in the clinical decision-making process. Here, we assessed 25 pathogenic and 15 neutral missense variants of the BRCA1 breast/ovarian cancer susceptibility gene in four BRCA1 functional assays. Next, we developed a novel approach that refines the variant ranking in these functional assays. Lastly, we developed a computational system that provides a probabilistic classification of variants, adapted to clinical interpretation. Using this system, the best functional assay exhibits a variant classification accuracy estimated at 93%. Additional theoretical simulations highlight the benefit of this ready-to-use system in the classification of variants after functional assessment, which should facilitate the consideration of functional evidences in the decision-making process after genetic testing. Finally, we demonstrate the versatility of the system with the classification of siRNAs tested for human cell growth inhibition in high throughput screening. PMID:27272900

  12. Generalized epilepsy with febrile seizures plus: Clinical and genetic analysis of three Serbian families

    Directory of Open Access Journals (Sweden)

    Ristić Aleksandar J.

    2005-01-01

    Full Text Available The results of clinical and genetic analysis of three Serbian families (pedigrees with autosomal dominant inheritance, incomplete penetrance and phenotypic features of GEFS+ are presented in this study. Mutation analysis of the SCN1A, SCN1B and GABRG2 genes was performed in all affected and some unaffected members of these three families. Twentysix exons of SCN1A, five exons of SCN1B and nine exons of GABRG2 were individually amplified using primers based on intronic sequence. PCR products were sequenced in both forward and reverse directions. Subsequently, the samples were run and analyzed using 377 DNA automated sequencer. No consanguinity was noticed. The MM and OM family members live in Republic of Srpska while KS family originates from the central Serbia. No mutations of the exons of SCN1A, SCN1B and GABRG2 genes were found in tested subjects. Obligate carriers in MM family (III-1, III-2, and III-4 exhibit variable expressivity or incomplete penetrance rather than proof of polygenetic inheritance. OM pedigree follows autosomal dominant pattern despite reduced penetrance. Bilinear transmission may assume the possibility of multigenetic mode of inheritance in KS family. The fact that all affected members in three Serbian families were negative for mutations in SCN1A, SCN1B and GABRG2 genes strongly supports the hypothesis of significant genetic heterogeneity of GEFS+. Recognizing GEFS+ on clinical grounds contributes to more precise integration of this syndrome into already existing classification of epileptic syndromes.

  13. Spinal muscular atrophy: Clinical spectrum and genetic mutations in Pakistani children

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    Shahnaz Ibrahim

    2012-01-01

    Full Text Available Background: In Pakistan the rate of consanguineous marriages is high, thus, the chance of incidence of autosomal recessive disorders is likely to be high. The aim of this study is to investigate the clinical characteristics and genetics of spinal muscular atrophy (SMA in children who presented to Aga Khan University, Karachi. Materials and Methods: This study was a retrospective review of the medical charts of children (neonate: 15 years with discharge diagnosis of SMA during last 10 years. Demographic features, consanguinity, and diagnostic analysis (including genetic analysis were noted. Results: During the study period 67 children had a discharge diagnosis of SMA. Werdnig Hoffman disease (SMA type I was the commonest variant seen in 37 (56% children. Overall 68% were infants. High parental consanguinity was observed in 68% of the study cohort. The history of delayed development and undiagnosed early death was observed in the families of 19 children. Genetic testing was performed in 22 (33% children. Survival motor neuron (SMN 1 gene deletion was found in 19 (86% of the 22 patients in whom the gene analysis was done and 13 (68% were also positive for neuronal apoptosis inhibitory proteins (NAIP deletion. Conclusion: SMA is not an uncommon neurodegenerative disorder in Pakistan and SMA type I was the most common type. SMN1 gene deletion was the most common genetic deletion found in this study. In addition, family history of developmental delay and frequent early deaths highlights the need for implementation of prenatal diagnosis for early detection, effective control, and management of this disorder in Pakistan.

  14. Genetic variation of human papillomavirus type 16 in individual clinical specimens revealed by deep sequencing.

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    Iwao Kukimoto

    Full Text Available Viral genetic diversity within infected cells or tissues, called viral quasispecies, has been mostly studied for RNA viruses, but has also been described among DNA viruses, including human papillomavirus type 16 (HPV16 present in cervical precancerous lesions. However, the extent of HPV genetic variation in cervical specimens, and its involvement in HPV-induced carcinogenesis, remains unclear. Here, we employ deep sequencing to comprehensively analyze genetic variation in the HPV16 genome isolated from individual clinical specimens. Through overlapping full-circle PCR, approximately 8-kb DNA fragments covering the whole HPV16 genome were amplified from HPV16-positive cervical exfoliated cells collected from patients with either low-grade squamous intraepithelial lesion (LSIL or invasive cervical cancer (ICC. Deep sequencing of the amplified HPV16 DNA enabled de novo assembly of the full-length HPV16 genome sequence for each of 7 specimens (5 LSIL and 2 ICC samples. Subsequent alignment of read sequences to the assembled HPV16 sequence revealed that 2 LSILs and 1 ICC contained nucleotide variations within E6, E1 and the non-coding region between E5 and L2 with mutation frequencies of 0.60% to 5.42%. In transient replication assays, a novel E1 mutant found in ICC, E1 Q381E, showed reduced ability to support HPV16 origin-dependent replication. In addition, partially deleted E2 genes were detected in 1 LSIL sample in a mixed state with the intact E2 gene. Thus, the methods used in this study provide a fundamental framework for investigating the influence of HPV somatic genetic variation on cervical carcinogenesis.

  15. Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status.

    Science.gov (United States)

    Schöpke, K; Gomez, A; Dunbar, K A; Swalve, H H; Döpfer, D

    2015-11-01

    Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (±0.11) and 0.52 (±0

  16. Clinical and genetic study of spinocerebellar ataxia type 7 in East Asian population

    Institute of Scientific and Technical Information of China (English)

    HAN Yan; YU Long; ZHENG Hui-min; GUAN Yang-tai

    2010-01-01

    Background Spinocerebellar ataxia type 7 (SCA7) is known as an autosomal dominant cerebellar ataxia; patients with genetically confirmed diagnoses of SCA7 have increased rapidly in recent years.However, SCA7 is a rare subtype of SCA, and most data available about SCA7 are those of white people.The aim of the present study was to systematically review the prevalence and clinical and genetic aspects of SCA7 patients in East Asian population.Methods A search for publications on SCA7 was performed by using the "PubMed" database with the published language limited in English.Publications mainly focusing on the prevalence of SCA7 in patients with SCA and the clinical and genetic features of SCA7 patients were fully reviewed and analyzed.Results The prevalence of SCA7 in SCA patients ranged from 0 to 7.7%, which was similar to those reported previously.The clinical manifestations were typically present at the 30's of its victims (median, 29 years; interquartile range (IQR),19.5-36.5 years), and the symptoms appeared 15 years ((15.17±4.22) years) earlier on average in the offspring than in the parents.Gait ataxia and visual impairment were both found in all patients of whom the clinical features were described.Mutant SCA7 alleles contained 40-100 CAG repeats, with a median of 47 repeats (IQR, 44.5-50.0); and the offspring had 13 more repeats on average compared with their parents (12.62±19.03).A strong negative correlation was found between CAG repeat size and the onset age of patients (r=-0.739, P=0.000).In addition, no significant difference was found in CAG repeat sizes between patients with visual impairment as the initial symptom and those with gait disturbance as their initial symptom (P=0.476).Conclusions The prevalence of SCA7 in SCA patients, the age at onset and CAG repeats of SCA7 patients in East Asia are consistent with those of white people.However, larger population study is needed to assess the correlation between the CAG repeat size and initial symptoms

  17. Clinical, radiologic, and genetic features of Korean patients with Mucopolysaccharidosis IVA

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    Na Hee Lee

    2012-11-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome is rare lysosomal storage disorder caused by &lt;I&gt;N&lt;/I&gt;-acetylgalactosamine- 6-sulfatase (GALNS deficiency. Only a few MPS IVA cases have been reported in the Korean literature; there is a paucity of research about clinical or radiologic findings for this disorder. Therefore, we studied clinical findings, radiological features, and genetic data of Korean MPS IVA patients for determining factors that may allow early diagnosis and that may thus improve the patients’ quality of life. &lt;B&gt;Method:&lt;/B&gt; MPS IVA was confirmed via assay for enzymatic activity of leukocytes in 10 patients. The &lt;I&gt;GALNS&lt;/I&gt; gene was analyzed. Patients’ charts were retrospectively reviewed for obtaining clinical features and evaluated for radiological skeletal surveys, echocardiography, pulmonary function test, and ophthalmologic test results. &lt;B&gt;Result:&lt;/B&gt; Nine patients had severe clinical phenotype, and 1 had an intermediate phenotype, on the basis of clinical phenotype criteria. Radiologic findings indicated skeletal abnormalities in all patients, especially in the hips and extremities. Eight patients had an odontoid hypoplasia, and 1 showed mild atlantoaxial subluxation and cord myelopathy. Genetic analysis indicated 10 different &lt;I&gt;GALNS&lt;/I&gt; mutations. Two mutations, c.451C&gt;A and c.1000C&gt;T, account for 37.5% (6/16 and 25% (4/16 of all mutations in this samples, respectively. &lt;B&gt;Conclusion:&lt;/B&gt; An understanding of the clinical and radiological features involved in MPS IVA may allow early diagnosis of MPS IVA. Adequate evaluations and therapy in the early stages may improve the quality of life of patients suffering from skeletal abnormalities and may reduce life-threatening effects of

  18. Do nuclear-encoded core subunits of mitochondrial complex I confer genetic susceptibility to schizophrenia in Han Chinese populations?

    OpenAIRE

    Xiao Li; Wen Zhang; Jinsong Tang; Liwen Tan; Xiong-jian Luo; Xiaogang Chen; Yong-Gang Yao

    2015-01-01

    Schizophrenia is one of the most prevalent psychiatric disorders with complex genetic etiology. Accumulating evidence suggests that energy metabolism and oxidative stress play important roles in the pathophysiology of schizophrenia. Dysfunction of mitochondrial respiratory chain and altered expression of complex I subunits were frequently reported in schizophrenia. To investigate whether nuclear-encoded core subunit genes of mitochondrial complex I are associated with schizophrenia, we perfor...

  19. Linking restless legs syndrome with Parkinson's disease: clinical, imaging and genetic evidence

    Directory of Open Access Journals (Sweden)

    Peeraully Tasneem

    2012-02-01

    Full Text Available Abstract Restless legs syndrome (RLS and Parkinson's disease (PD are both common neurological disorders. There has been much debate over whether an etiological link between these two diseases exists and whether they share a common pathophysiology. Evidence pointing towards a link includes response to dopaminergic agents in PD and RLS, suggestive of underlying dopamine dysfunction in both conditions. The extrastriatal dopaminergic system, in particular altered spinal dopaminergic modulation, may be variably involved in PD patients with RLS symptoms. In addition, there is now evidence that the nigrostriatal system, primarily involved in PD, is also affected in RLS. Furthermore, an association of RLS with the parkin mutation has been suggested. The prevalence of RLS has also been reported to be increased in other disorders of dopamine regulation. However, clinical association studies and functional imaging have produced mixed findings. Conflicting accounts of emergence of RLS and improvement in RLS symptoms after deep brain stimulation (DBS also contribute to the uncertainty surrounding the issue. Among the strongest arguments against a common pathophysiology is the role of iron in RLS and PD. While elevated iron levels in the substantia nigra contribute to oxidative stress in PD, RLS is a disorder of relative iron deficiency, with symptoms responding to replacement therapy. Recent ultrasonography studies have suggested that, despite overlapping clinical features, the mechanisms underlying idiopathic RLS and RLS associated with PD may differ. In this review, we provide a concise summary of the clinical, imaging and genetic evidence exploring the link between RLS and PD.

  20. Practical aspects of recruitment and retention in clinical trials of rare genetic diseases: the phenylketonuria (PKU) experience.

    Science.gov (United States)

    DeWard, Stephanie J; Wilson, Ashley; Bausell, Heather; Volz, Ashley S; Mooney, Kimberly

    2014-02-01

    Bringing treatments for rare genetic diseases to patients requires clinical research. Despite increasing activism from patient support and advocacy groups to increase access to clinical research studies, connecting rare disease patients with the clinical research opportunities that may help them has proven challenging. Chief among these challenges are the low incidence of these diseases resulting in a very small pool of known patients with a particular disease, difficulty of diagnosing rare genetic diseases, logistical issues such as long distances to the nearest treatment center, and substantial disease burden leading to loss of independence. Using clinical studies of phenylketonuria as an example, this paper discusses how, based on the authors' collective experience, partnership among clinicians, patients, study coordinators, genetic counselors, dietitians, industry, patient support groups, and families can help overcome the challenges of recruiting and retaining patients in rare disease clinical trials. We discuss specific methods of collaboration, communication, and education as part of a long-term effort to build a community committed to advancing the medical care of patients with rare genetic diseases. By talking to patients and families regularly about research initiatives and taking steps to make study participation as easy as possible, rare disease clinic staff can help ensure adequate study enrollment and successful study completion. PMID:24014152

  1. Four Years Analysis of Cancer Genetic Clinics Activity in France from 1994 to 1997: A Survey on 801 Patients

    OpenAIRE

    Hagay Sobol; Yves-Jean Bignon; Catherine Bonaiti; Jean Cuisenier; Christine Lasset; Alain Lortholary; Catherine Noguès; Dominique Stoppa-Lyonnet; François Eisinger; The French Cooperative Network/Groupe Génétique et Cancer de la Fédération Nationale des Centres de Lutte Contre le Cancer

    2002-01-01

    AIM: In order to evaluate the characteristics and the evolution of cancer genetics activity in France, a survey was conducted at the national level during a period of 4 years from 1994 to 1997 through the French Cooperative Network, a multidisciplinary group formed to investigate inherited tumors. METHOD: A questionnaire was sent to all the 29 French non-specialized cancer genetic clinics to evaluate activity during a period of 4 consecutive weeks each year from 1994 to 1997. Items concerning...

  2. Clinical and genetic analysis of two Chinese families with benign familial neonatal convulsions

    Institute of Scientific and Technical Information of China (English)

    LI Haiyan; TANG Beisha; XIA Kun; CAO Guifang; SHEN Lu; JIANG Hong; PAN Qian; SONG Yanmin; CAI Fang

    2005-01-01

    Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant inherited epilepsy syndrome. Two voltagegated potassium channel genes, KCNQ2 and KCNQ3, have been identified as the genes responsible for BFNC. Here we report two Chinese families with clinical histories of typical BFNC. Using six microsatellite markers, two located at KCNQ2 locus and four at KCNQ3 locus, linkage analysis was performed in the two families, which excluded the linkage of BFNC to KCNQ3, but could not exclude the linkage to KCNQ2. Direct DNA sequencing of the KCNQ2 gene in the two families was performed, and two formerly unknown polymorphisms were identified, but no KCNQ2 mutation was found in the two families. Our study suggests the genetic heterogeneity in Chinese families with BFNC and proves the existence of a new gene locus for BFNC.

  3. Genetic variation of low-density lipoprotein-cholesterol and its clinical implications

    Institute of Scientific and Technical Information of China (English)

    Tsung O. Cheng

    2005-01-01

    @@ Plasma lipids are controlled by genes and play an important role in the development of atherosclerosis. Dysplipidemia is an important risk factor for coronary artery disease (CAD). Coronary artery disease is the leading cause of mortality and morbidity in the developed world. More than 14 million Americans are afflicted with clinically significant CAD.1 To illustrate the impact of CAD in developed countries, the medical and societal costs of CAD in the United States alone are in excess of $90 billion annually.1 More than 600 000 Americans each year develop new cardiac events, more than 10% of which occur in Americans <50 years of age.1 Identifying genetic predisposition to early onset of CAD could help in understanding basic disease mechanism, guiding targeted preventive efforts, and planning appropriate therapeutic strategies.

  4. Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family.

    Science.gov (United States)

    Tabernero, C; Polo, J M; Sevillano, M D; Muñoz, R; Berciano, J; Cabello, A; Báez, B; Ricoy, J R; Carpizo, R; Figols, J; Cuadrado, N; Claveria, L E

    2000-06-01

    The clinical presentation and evolution, neuropathological findings, and genotyping of three members of a Spanish family affected with fatal familial insomnia are reported. The mother and two of her offspring developed a rapidly evolving disease with insomnia and behavioural disorders as the initial symptoms and died between 5 and 10 months after the onset of the illness. Frontal brain biopsy in the mother disclosed only non-significant spongiosis, and full neuropathological examination of her offspring showed thalamic and olivary degeneration with isolated focal cortical spongiosis. Genetic examination could only be performed in the contemporary patients and both harboured the prion protein (PrP) 178Asn mutation and homozygous 129 Met/Met genotype. PMID:10811705

  5. [Retracted] Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy.

    Science.gov (United States)

    Liu, Xinhong; Wu, Huamin; Gong, Jian; Wang, Tao; Yan, Chuanzhu

    2016-07-01

    We wish to retract our article entitled 'Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy' published in Molecular Medicine Reports 13: 4273-4278, 2016. The article was submitted by the first author, Xinhong Liu, without the prior knowledge of the corresponding author, Chuanzhu Yan, or the other authors included on the paper. Furthermore, the details of the paper were not discussed by the authors prior to the submission, and all are in agreement that the paper contains data therein (and interpretations thereof) which are either inaccurate or inappropriate. All the authors agree to this retraction, and we apologize for the inconvenience caused in this regard.[the original article was published in the Molecular Medicine Reports 13: 4273-4278, 2016; DOI: 10.3892/mmr.2016.5047]. PMID:27176730

  6. Emerging Histopathological and Genetic Parameters of Pituitary Adenomas: Clinical Impact and Recommendation for Future WHO Classification.

    Science.gov (United States)

    Saeger, W; Petersenn, S; Schöfl, C; Knappe, U J; Theodoropoulou, M; Buslei, R; Honegger, J

    2016-06-01

    The review assesses immunohistochemical findings of somatostatin receptors and of metalloproteinases in different pituitary adenoma types and the significance of molecular genetic data. Current evidence does not support routine immunohistochemical assessment of somatostatin or dopamine receptor subtype expression on hormone-secreting or nonfunctioning pituitary adenomas. Further prospective studies are needed to define its role for clinical decision making. Until then we suggest to restrict membrane receptor profiling to individual cases or for study purposes. The problems of adenoma expansion and invasion are discussed. Despite partially contradictory publications, proteases clearly play a major role in permission of infiltrative growth of pituitary adenomas. Therefore, detection of at least MMP-2, MMP-9, TIMP-2, and uPA seems to be justified. Molecular characterization is important for familial adenomas, adenomas in MEN, Carney complex, and McCune-Albright syndrome and can gain insight into pathogenesis of sporadic adenomas. PMID:26874696

  7. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Leoz ML

    2015-04-01

    Full Text Available Maria Liz Leoz, Sabela Carballal, Leticia Moreira, Teresa Ocaña, Francesc Balaguer Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Barcelona, Catalonia, Spain Abstract: Familial adenomatous polyposis (FAP is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP. FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC, and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP. Keywords: colorectal cancer, familial adenomatous polyposis, MAP, APC, MUTYH

  8. [Syndrome Leigh caused by mutations in the SURF1 gene: clinical and molecular-genetic characteristics].

    Science.gov (United States)

    Tsygankova, P G; Mikhaĭlova, S V; Zakharova, E Iu; Pichkur, N A; Il'ina, E S; Nikolaeva, E A; Rudenskaia, G E; Dadali, E L; Kolpakchi, L M; Fedoniuk, I D; Matiushchenko, G N

    2010-01-01

    Syndrome Leigh (SL) or subacute necrotizing encephalomyelopathy - is a rare hereditary genetically heterogeneous disease from the group of mitochondrial encephalomyopathies. Twenty-seven children with SL were examined using clinical, laboratory (measuring lactate levels), MRI and molecular-genetic (polymerase chain reaction genotyping of 9 exons of the SURF1 gene) studies. The mean age of manifestation was 11,6 months. The main manifestations of SL were: delay of psychomotor development, diffuse muscle hypertonic, cerebellar syndrome, ophthalmoparesis, hypertrichosis. The disease had a progressive course with the loss of acquired skills. The blood lactate concentration was increased on average up to 3,1 mM/ml (from 1,9 to 5,1 mM/ml) compared to normal values (1,8 mM/ml). Brain MRI revealed the subcortical and cortical atrophy (80% of cases), symmetrical distinctly delineated hyperintense lesions on T2-weighted images (demyelization) in the basal ganglia and the brain stem (50%), as well as in the cerebellum (25%). Genotyping identified 7 different mutations. The most frequent (64,8%) was the deletion of 2 nucleotides (845delCT) in exon 8 that was in line with early data of Polish researchers thus indicating the Slavic origin of this mutation. Other mutations (574-575insCTGT, 311-321del10insAT and IVS8-1G>) were also frequent in the Russian population. PMID:20436434

  9. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

    Directory of Open Access Journals (Sweden)

    Dichter Gabriel S

    2012-07-01

    Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

  10. Clinical Presentation and Genetic Paradigm of Diffuse Infiltrating Retinoblastoma: A Review.

    Science.gov (United States)

    Traine, Peter G; Schedler, Katharina J; Rodrigues, Eduardo B

    2016-04-01

    Retinoblastoma is the most common childhood cancer. Thanks to modern technology and good medical access, mortality in Europe has decreased to about 5%. Diffuse infiltrating retinoblastoma is a very rare subtype of this neoplasm and is characterized by its atypical growth pattern. Diffuse infiltrating retinoblastoma may mimic other more innocuous diseases and may therefore be misdiagnosed. The purpose of this paper was to provide a short review of the main symptoms of diffuse infiltrating retinoblastoma presenting to the ophthalmologist and give a comparison to typical retinoblastoma. The second purpose was to set up a discussion of the genetic paradigm of diffuse infiltrating retinoblastoma. It has often been described to occur sporadically; however, in the last years, it has been shown that it might be heritable. A literature search concerning diffuse infiltrating retinoblastoma considering English, German and Spanish cases and case series identified 77 patients. Moreover, an overview of general data, main symptoms, clinical findings and initial working diagnoses or referral diagnoses is given. Males were significantly more often affected than females. Diffuse infiltrating retinoblastoma can be heritable. Genetic analysis should be offered to the patient and relatives. Interdisciplinary medical follow-up care is needed to detect associated cancers. PMID:27239450

  11. Clinical and genetic features of human prion diseases in Catalonia: 1993-2002.

    Science.gov (United States)

    Sanchez-Valle, R; Nos, C; Yagüe, J; Graus, F; Domínguez, A; Saiz, A

    2004-10-01

    We describe the clinical and genetic characteristics of the 85 definite or probable human prion diseases cases died between January 1993 and December 2002 in Catalonia (an autonomous community of Spain, 6 million population). Seventy-three (86%) cases were sporadic Creutzfeld-Jakob diseases (sCJD) (49 definite, 24 probable), with a median age at onset of 66 years. The clinical presentation was dementia in 29 cases, ataxia in 14 and visual symptoms in five. The median survival was 3 months. The 14-3-3 assay was positive in 93% cases, 62% presented periodic sharp wave complexes (PSWC) in EEG but only 18% the typical signs on MRI. Forty-eight sCJD were studied for codon 129 PRNP polymorphism: 69% were methionine/methionine (M/M), 14.5% valine/valine (V/V) and 16.5% M/V. Six out of seven V/V cases did not present PSWC and in two survival was longer than 20 months. Eleven cases (13%) were genetic: five familial fatal insomnia and six familial CJD (fCJD). Up to four (67%) fCJD lacked family history of disease, two presented seizures early at onset and one neurosensorial deafness. The only iatrogenic case was related to a dura mater graft. No case of variant CJD was registered. The study confirms in our population the consistent pattern reported worldwide on human prion diseases. Atypical features were seen more frequently in sporadic 129 V/V CJD and fCJD cases. PMID:15469448

  12. Autosomal recessive primary microcephaly (MCPH: clinical manifestations, genetic heterogeneity and mutation continuum

    Directory of Open Access Journals (Sweden)

    Hassan Muhammad J

    2011-06-01

    Full Text Available Abstract Autosomal Recessive Primary Microcephaly (MCPH is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7 for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1 orientation of mitotic spindles, 2 chromosome condensation mechanism during embryonic neurogenesis, 3 DNA damage-response signaling, 4 transcriptional regulations and microtubule dynamics, 5 certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder.

  13. Genetic variation in plant CYP51s confers resistance against voriconazole, a novel inhibitor of brassinosteroid-dependent sterol biosynthesis.

    Science.gov (United States)

    Rozhon, Wilfried; Husar, Sigrid; Kalaivanan, Florian; Khan, Mamoona; Idlhammer, Markus; Shumilina, Daria; Lange, Theo; Hoffmann, Thomas; Schwab, Wilfried; Fujioka, Shozo; Poppenberger, Brigitte

    2013-01-01

    Brassinosteroids (BRs) are plant steroid hormones with structural similarity to mammalian sex steroids and ecdysteroids from insects. The BRs are synthesized from sterols and are essential regulators of cell division, cell elongation and cell differentiation. In this work we show that voriconazole, an antifungal therapeutic drug used in human and veterinary medicine, severely impairs plant growth by inhibiting sterol-14α-demethylation and thereby interfering with BR production. The plant growth regulatory properties of voriconazole and related triazoles were identified in a screen for compounds with the ability to alter BR homeostasis. Voriconazole suppressed growth of the model plant Arabidopsis thaliana and of a wide range of both monocotyledonous and dicotyledonous plants. We uncover that voriconazole toxicity in plants is a result of a deficiency in BRs that stems from an inhibition of the cytochrome P450 CYP51, which catalyzes a step of BR-dependent sterol biosynthesis. Interestingly, we found that the woodland strawberry Fragaria vesca, a member of the Rosaceae, is naturally voriconazole resistant and that this resistance is conferred by the specific CYP51 variant of F. vesca. The potential of voriconazole as a novel tool for plant research is discussed. PMID:23335967

  14. Genetic variation in plant CYP51s confers resistance against voriconazole, a novel inhibitor of brassinosteroid-dependent sterol biosynthesis.

    Directory of Open Access Journals (Sweden)

    Wilfried Rozhon

    Full Text Available Brassinosteroids (BRs are plant steroid hormones with structural similarity to mammalian sex steroids and ecdysteroids from insects. The BRs are synthesized from sterols and are essential regulators of cell division, cell elongation and cell differentiation. In this work we show that voriconazole, an antifungal therapeutic drug used in human and veterinary medicine, severely impairs plant growth by inhibiting sterol-14α-demethylation and thereby interfering with BR production. The plant growth regulatory properties of voriconazole and related triazoles were identified in a screen for compounds with the ability to alter BR homeostasis. Voriconazole suppressed growth of the model plant Arabidopsis thaliana and of a wide range of both monocotyledonous and dicotyledonous plants. We uncover that voriconazole toxicity in plants is a result of a deficiency in BRs that stems from an inhibition of the cytochrome P450 CYP51, which catalyzes a step of BR-dependent sterol biosynthesis. Interestingly, we found that the woodland strawberry Fragaria vesca, a member of the Rosaceae, is naturally voriconazole resistant and that this resistance is conferred by the specific CYP51 variant of F. vesca. The potential of voriconazole as a novel tool for plant research is discussed.

  15. Dissociative experiences in obsessive-compulsive disorder and trichotillomania: clinical and genetic findings.

    Science.gov (United States)

    Lochner, Christine; Seedat, Soraya; Hemmings, Sian M J; Kinnear, Craig J; Corfield, Valerie A; Niehaus, Dana J H; Moolman-Smook, Johanna C; Stein, Dan J

    2004-01-01

    A link between dissociation proneness in adulthood and self-reports of childhood traumatic events (including familial loss in childhood, sexual/physical abuse and neglect) has been documented. Several studies have also provided evidence for an association between dissociative experiences and trauma in patients with various psychiatric disorders, including post-traumatic stress disorder, borderline personality, dissociative identity and eating disorders. Based on the relative paucity of data on dissociation and trauma in obsessive-compulsive disorder (OCD) and trichotillomania (TTM), the primary objective of this study was to examine the relationship between trauma and dissociative experiences (DE) in these two diagnostic groups. Furthermore, the availability of clinical and genetic data on this sample allowed us to explore clinical and genetic factors relevant to this association. A total of 110 OCD and 32 TTM patients were compared with respect to the degree of dissociation (using the Dissociative Experiences Scale [DES]) and childhood trauma (using the Childhood Trauma Questionnaire [CTQ]). Patients were classified on the DES as either "high" (mean DES score >/= 30) or "low" (mean DES score sexual abuse, and physical neglect. In the OCD group, high dissociators were significantly younger than low dissociators, and significantly more high dissociators than low dissociators reported a lifetime (current and past) history of tics (P disorder (P =.027). In the TTM group, significantly more high dissociators than low dissociators reported (lifetime) kleptomania (P =.005) and depersonalisation disorder (P =.005). In the Caucasian OCD patients (n = 114), investigation of genetic polymorphisms involved in monoamine function revealed no significant differences between high and low dissociator groups. This study demonstrates a link between childhood trauma and DE in patients with OCD and TTM. High dissociative symptomatology may be present in a substantial proportion of

  16. Severe myoclonic epilepsy of infancy (Dravet syndrome: Clinical and genetic features of nine Turkish patients

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    Meral Özmen

    2011-01-01

    Full Text Available Purpose: Mutations of the a-1 subunit sodium channel gene (SCN1A cause severe myoclonic epilepsy of infancy (SMEI. To date, over 300 mutations related to SMEI have been described. In the present study, we report new SCN1A mutations and the clinical features of SMEI cases. Materials and Methods: We studied the clinical and genetic features of nine patients diagnosed with SMEI at the Pediatric Neurology Department of Istanbul Medical Faculty. Results: Five patients had nonsense mutations, two had missense mutations, one had a splice site mutation and one had a deletion mutation of the SCN1A gene. Mutations at c.3705+5G splice site, p.trip153X nonsense mutation and deletion at c.2416_2946 have not been previously described. The seizures started following whole cell pertussis vaccination in all patients. The seizures ceased in one patient and continued in the other eight patients. Developmental regression was severe in three patients, with frequent status epilepticus. The type of mutation was not predictive for the severity of the disease. Two of the three patients with severe regression had nonsense and missense mutations. Conclusions : Dravet syndrome can be result of several different types of mutation in SCN1A gene. Onset of the seizures after pertussis vaccination is an important clue for the diagnosis and neuro- developmental delay should be expected in all patients.

  17. Clinical and genetic study of a Chinese family with spinocerebellar ataxia type 7

    Directory of Open Access Journals (Sweden)

    Han Yan

    2010-01-01

    Full Text Available Spinocerebellar ataxia 7 (SCA7 is a rare disease, and only few SCA7 families have been reported, especially from East Asia. Clinical features of a genetically confirmed SCA7 Chinese family were evaluated. The onset of the disease varied from 4 years to 48 years, and the initial presenting feature was cerebellar ataxia or visual impairment, or both. There were abnormal findings on fundus photography, electroretinogram, flash visual evoked potential and oscillatory potentials. Abnormal mitochondria were also found in skeletal muscle or liver biopsies. The number of cytosine adenine guanine (CAG repeats ranged from 50 to 97, and the length of CAG repeat was inversely correlated with the age of onset (r=-0.867, P=0.025. Conclusion: The clinical manifestations and SCA7 gene of SCA7 patients were homogeneous in this study. Larger CAG repeats had not only resulted in earlier onset, but also related to the rapid progression and severity of the disease. Abnormal mitochondria may be a common finding in biopsy studies of various organs in SCA7 patients.

  18. Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

    Institute of Scientific and Technical Information of China (English)

    Yun Wu; Ying Hu; Peng You; Yu-Jing Chi; Jian-Hua Zhou; Yuan-Yuan Zhang; Yu-Lan Liu

    2016-01-01

    Background:Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions.Methods:We recruited aspirin takers as the exposed group and healthy volunteers as the control group.The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy,including erosion,ulcer or bleeding of the esophagus,stomach,or duodenum;subgroup B as no injury of the gastric mucosa was detected by gastroscopy.Clinical information was collected,and 53 single nucleotide polymorphisms were evaluated.Results:Among 385 participants,234 were in the aspirin-exposed group.According to gastroscopy,82 belonged to subgroup A,91 belonged to subgroup B,and gastroscopic results of 61 participants were not available.Using the Chi-square test and logistic regression,we found that peptic ulcer history (odds ratio [OR] =5.924,95% confidence intervals [CI]:2.115-16.592),dual anti-platelet medication (OR =3.443,95% CI:1.154-10.271),current Helicobacterpylori infection (OR =2.242,95% CI:1.032-4.870),male gender (OR =2.211,95% CI:1.027-4.760),GG genotype ofrs2243086 (OR =4.516,95% CI:1.180-17.278),and AA genotype ofrs 1330344 (OR =2.178,95% CI:1.016-4.669) were more frequent in subgroup A than subgroup B.In aspirin users who suffered from upper gastrointestinal bleeding,the frequency of the TT genotype ofrs2238631 and TT genotype ofrs2243100 was higher than in those without upper gastrointestinal bleeding.Conclusions:Peptic ulcer history,dual anti-platelet medication,H.pylori current infection,and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury.GG genotype of rs2243086 and AA genotype of rs 1330344 were possible genetic risk factors.TT genotype ofrs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users.

  19. Clinical, histopathological and genetic studies in a case of fatal familial insomnia with review of the literature

    OpenAIRE

    Peng, Bin; Zhang, Shenqi; Dong, Hongjuan; Lu, Zuneng

    2015-01-01

    To explore clinical, histopathological and genetic features of a case with fatal familial insomnia (FFI) and review the related literatures. A middle-aged woman who complained of “insomnia for 9 months and psychosis for 3 months” was suspicious of FFI. The clinical features of the patient were analyzed, and the dead patient was examined by autopsy and the brain tissues were obtained for histopathological studies, and the blood samples from the patient and some of her familial members were col...

  20. Impact of HFE genetic testing on clinical presentation of hereditary hemochromatosis: new epidemiological data

    Directory of Open Access Journals (Sweden)

    Ka Chandran

    2005-06-01

    Full Text Available Abstract Background Hereditary hemochromatosis (HH is a common inherited disorder of iron metabolism in Northern European populations. The discovery of a candidate gene in 1996 (HFE, and of its main mutation (C282Y, has radically altered the way to diagnose this disease. The aim of this study was to assess the impact of the HFE gene discovery on the clinical presentation and epidemiology of HH. Methods We studied our cohort of 415 patients homozygous for the C282Y allele and included in a phlebotomy program in a blood centre in western Brittany, France. Results In this cohort, 56.9% of the patients were male and 21.9% began their phlebotomy program before the implementation of the genetic test. A significant decrease in the sex ratio was noticed following implementation of this DNA test, from 3.79 to 1.03 (p -5, meaning that the proportion of diagnosed females relatives to males greatly increased. The profile of HH patients at diagnosis changed after the DNA test became available. Serum ferritin and iron values were lower and there was a reduced frequency of clinical signs displayed at diagnosis, particularly skin pigmentation (20.1 vs. 40.4%, OR = 0.37, p Conclusion This study highlights the importance of the HFE gene discovery, which has simplified the diagnosis of HH and modified its clinical presentation and epidemiology. This study precisely measures these changes. Enhanced diagnosis of HFE-related HH at an early stage and implementation of phlebotomy treatment are anticipated to maintain normal life expectancy for these patients.

  1. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P; Blichfeldt, S; Petersen, M B; Tommerup, Niels; Brøndum-Nielsen, K

    1997-01-01

    recurrence has been reported. In rare cases, PWS is associated with lack of gene expression from the paternal allele due to an imprinting defect. We report the clinical features and the molecular genetic analysis of the first Danish child with PWS due to a defect of the putative imprinting centre (IC). When...

  2. Non-inflammatory destructive periodontal disease: a clinical, microbiological, immunological and genetic investigation

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Repeke

    2012-02-01

    Full Text Available Periodontitis comprises a group of multifactorial diseases in which periodontopathogens accumulate in dental plaque and trigger host chronic inflammatory and immune responses against periodontal structures, which are determinant to the disease outcome. Although unusual cases of non-inflammatory destructive periodontal disease (NIDPD are described, their pathogenesis remains unknown. A unique NIDPD case was investigated by clinical, microbiological, immunological and genetic tools. The patient, a non-smoking dental surgeon with excessive oral hygiene practice, presented a generalized bone resorption and tooth mobility, but not gingival inflammation or occlusion problems. No hematological, immunological or endocrine alterations were found. No periodontopathogens (A. actinomycetemcomitans, P. gingivalis, F. nucleatum and T. denticola or viruses (HCMV, EBV-1 and HSV-1 were detected, along with levels of IL-1β and TNF-a in GCF compatible with healthy tissues. Conversely ALP, ACP and RANKL GCF levels were similar to diseased periodontal sites. Genetic investigation demonstrated that the patient carried some SNPs, as well HLA-DR4 (*0404 and HLA-B27 alleles, considered risk factors for bone loss. Then, a less vigorous and diminished frequency of toothbrushing was recommended to the patient, resulting in the arrest of alveolar bone loss, associated with the return of ALP, ACP and RANKL in GCF to normality levels. In conclusion, the unusual case presented here is compatible with the previous description of NIDPD, and the results that a possible combination of excessive force and frequency of mechanical stimulation with a potentially bone loss prone genotype could result in the alveolar bone loss seen in NIDPD.

  3. Genetic and physical fine-mapping of the Sc locus conferring indica-japonica hybrid sterility in rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    YANG Cunyi; CHEN Zhongzheng; ZHUANG Chuxiong; MEI Mantong; LIU Yaoguang

    2004-01-01

    Hybrid sterility is a major hindrance to utilizing the heterosis in indica-japonica hybrids. To isolate a gene Sc conferring the hybrid sterility, the locus was mapped using molecular markers and an F2 population derived from a cross between near isogenic lines. A primary linkage analysis showed that Sc was linked closely with 4 markers on chromosome 3, on which the genetic distance between a marker RG227 and Sc was 0.07 cM. Chromosome walking with a rice TAC genomic library was carried out using RG227 as a starting probe, and a contig of ca. 320 kb covering the Sc locus was constructed. Two TAC clones, M45E14 and M90J01 that might cover the Sc locus, were partially sequenced. By searching the rice sequence databases with sequences of the TACs and RG227 a japonica rice BAC sequence, OSJNBb0078P24 was identified. By comparing the TAC and BAC sequences, six new PCR-based markers were developed. With these markers the Sc locus was further mapped to a region of 46 kb. The results suggest that the BAC OSJNBb0078P24 and TAC M45E14 contain the Sc gene. Six ORFs were predicted in the focused 46-kb region.

  4. Mitochondrial DNA copy number, but not haplogroup, confers a genetic susceptibility to leprosy in Han Chinese from Southwest China.

    Directory of Open Access Journals (Sweden)

    Dong Wang

    Full Text Available BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an unculturable pathogen with an exceptionally eroded genome. The high level of inactivation of gene function in M. leprae, including many genes in its metabolic pathways, has led to a dependence on host energy production and nutritional products. We hypothesized that host cellular powerhouse--the mitochondria--may affect host susceptibility to M. leprae and the onset of clinical leprosy, and this may be reflected by mitochondrial DNA (mtDNA background and mtDNA copy number. METHODS: We analyzed the mtDNA sequence variation of 534 leprosy patients and 850 matched controls from Yunnan Province and classified each subject by haplogroup. mtDNA copy number, taken to be proportional to mtDNA content, was measured in a subset of these subjects (296 patients and 231 controls and 12 leprosy patients upon diagnosis. RESULTS: Comparison of matrilineal components of the case and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that lepromatous leprosy patients had a significantly higher mtDNA content than controls (P = 0.008. Past medical treatments had no effect on the alteration of mtDNA copy number. CONCLUSIONS: Our results suggested that mtDNA content, but not haplogroup, affects leprosy and this influence is limited to the clinical subtype of lepromatous leprosy.

  5. Improving service delivery by evaluation of the referral pattern and capacity in a clinical genetics setting.

    Science.gov (United States)

    McCann, Emma; Baines, Elizabeth A; Gray, Jonathon R; Procter, Annie M

    2009-08-15

    Quality improvement in specialist services such as clinical genetics is challenging largely due to the complexity of the service and the difficulty in obtaining accurate, reproducible, and measurable data. The objectives were to evaluate the pattern of referrals to the All Wales Medical Genetics Service (AWMGS) North Wales Genetics team based in three separate hospitals, define the capacity of the team and implement change to improve equity, timeliness and efficiency of care delivery to patients. The methodology required collating the monthly referral rates retrospectively for each center over a 2.5-year period and plotting on statistical process control charts. Process mapping of the referral process in each center was undertaken, differences documented and a common pathway implemented. "Did not attend" and "time to first appointment" rates were also measured in one center. PDSA methodology was used to implement "patient focused booking." The results show that the range for referral rates in any given month for each center was 3-33 referrals. The range for referral rate for the whole team was 18-64 per month. Since January 2004 the average number of monthly referrals to the North Wales service has increased by 50%. The potential range in monthly referrals varies between centers and the range of the variability has also increased also in two out of the three centers. Introduction of Patient Focused Booking reduced the "Failed to Attend" rate and 100% of patients were offered a choice of appointments. In addition 100% had a first face-to-face contact within 6 weeks if they chose. The measurement of improvement involved firstly introducing a series of continuous measures to provide a baseline for the process prior to the implementation of any changes and secondly to indicate the impact of the changes following implementation. The measures implemented included process (referrals numbers, percentage of patients offered a choice of appointments), outcome (percentage of

  6. Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

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    Relu Cocoş

    Full Text Available Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1 ∶ 1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18 ± 1 years showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

  7. Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.

    Science.gov (United States)

    Medici, Marco; Porcu, Eleonora; Pistis, Giorgio; Teumer, Alexander; Brown, Suzanne J; Jensen, Richard A; Rawal, Rajesh; Roef, Greet L; Plantinga, Theo S; Vermeulen, Sita H; Lahti, Jari; Simmonds, Matthew J; Husemoen, Lise Lotte N; Freathy, Rachel M; Shields, Beverley M; Pietzner, Diana; Nagy, Rebecca; Broer, Linda; Chaker, Layal; Korevaar, Tim I M; Plia, Maria Grazia; Sala, Cinzia; Völker, Uwe; Richards, J Brent; Sweep, Fred C; Gieger, Christian; Corre, Tanguy; Kajantie, Eero; Thuesen, Betina; Taes, Youri E; Visser, W Edward; Hattersley, Andrew T; Kratzsch, Jürgen; Hamilton, Alexander; Li, Wei; Homuth, Georg; Lobina, Monia; Mariotti, Stefano; Soranzo, Nicole; Cocca, Massimiliano; Nauck, Matthias; Spielhagen, Christin; Ross, Alec; Arnold, Alice; van de Bunt, Martijn; Liyanarachchi, Sandya; Heier, Margit; Grabe, Hans Jörgen; Masciullo, Corrado; Galesloot, Tessel E; Lim, Ee M; Reischl, Eva; Leedman, Peter J; Lai, Sandra; Delitala, Alessandro; Bremner, Alexandra P; Philips, David I W; Beilby, John P; Mulas, Antonella; Vocale, Matteo; Abecasis, Goncalo; Forsen, Tom; James, Alan; Widen, Elisabeth; Hui, Jennie; Prokisch, Holger; Rietzschel, Ernst E; Palotie, Aarno; Feddema, Peter; Fletcher, Stephen J; Schramm, Katharina; Rotter, Jerome I; Kluttig, Alexander; Radke, Dörte; Traglia, Michela; Surdulescu, Gabriela L; He, Huiling; Franklyn, Jayne A; Tiller, Daniel; Vaidya, Bijay; de Meyer, Tim; Jørgensen, Torben; Eriksson, Johan G; O'Leary, Peter C; Wichmann, Eric; Hermus, Ad R; Psaty, Bruce M; Ittermann, Till; Hofman, Albert; Bosi, Emanuele; Schlessinger, David; Wallaschofski, Henri; Pirastu, Nicola; Aulchenko, Yurii S; de la Chapelle, Albert; Netea-Maier, Romana T; Gough, Stephen C L; Meyer Zu Schwabedissen, Henriette; Frayling, Timothy M; Kaufman, Jean-Marc; Linneberg, Allan; Räikkönen, Katri; Smit, Johannes W A; Kiemeney, Lambertus A; Rivadeneira, Fernando; Uitterlinden, André G; Walsh, John P; Meisinger, Christa; den Heijer, Martin; Visser, Theo J; Spector, Timothy D; Wilson, Scott G; Völzke, Henry; Cappola, Anne; Toniolo, Daniela; Sanna, Serena; Naitza, Silvia; Peeters, Robin P

    2014-02-01

    Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8)) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, P = 8.1×10(-8)), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9×10(-6)), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5×10(-4)). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2×10(-7) and OR: 1.25, 95% CI 1.12-1.39, P = 6.2×10(-5)). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9×10(-3)). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why

  8. Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.

    Directory of Open Access Journals (Sweden)

    Marco Medici

    2014-02-01

    Full Text Available Autoimmune thyroid diseases (AITD are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis, as well as autoimmune hyperthyroidism (Graves' disease. As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8 were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores of these variants on (subclinical hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, P = 8.1×10(-8, a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9×10(-6, as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5×10(-4. The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2×10(-7 and OR: 1.25, 95% CI 1.12-1.39, P = 6.2×10(-5. The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9×10(-3. This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why

  9. Clinical profile, diagnostic delay, and genetic make-up of cystic fibrosis in Kashmir, India

    Directory of Open Access Journals (Sweden)

    Tasaduq Ahmad Mir

    2011-01-01

    Full Text Available Objectives: This observational study was done to describe the clinical profile, and delays in diagnosing cystic fibrosis (CF disease in Kashmir, India. Materials and Methods : A total of 6758 patients between the ages of 0 and 19 years were registered over a period of 1 year. Out of these, 150 patients suspected of having CF, on clinical grounds, were subjected to pilocarpine iontophoresis, and later on genetic evaluation. Apart from these specific tests, these patients were subjected to laboratory tests like blood counts, blood sugar, KFT, LFT, pancreatic function test, serum electrolytes, and chloride, urine, throat swab, blood culture, ABG analysis, chest and paranasal X-rays. In addition, sonographic evaluation of abdominal organs was carried out to know the status of internal organs. A polymerase chain reaction (PCR-based test was used for the identification of CF mutation. Results: CF was diagnosed in three (0.8% patients. Median age of presentation of CF was 78 months. Family history suggestive of CF was present in one (33.3% and consanguinity in three (100% patients. Common clinical manifestations at the time of presentation included recurrent pneumonia in three (100%, failure to thrive in three (100%, recurrent diarrhea in one (33.3% patients. General physical examination showed pallor in three (100%, malnutrition in three (100%, and clubbing in two (66.7% patients. Examination of respiratory tract revealed hyperinflation in two (66.7%, rhinitis in two (66.7%, and creptations in two (66.7% patients. Sonography of abdominal organs revealed pancreatic cysts in one (33.3%, hyperechoeic and increased liver span in two (66.7%, and small gallbladder in one (33.3%. Staphylococcus aureus was cultured from sputum in one (33.3%, pseudomonas aeruginosa in one (33.3% patients. Delta F508 mutation was present in one (33.3% patient. Conclusion: CF may be more common in Kashmir and other parts of Asia, than indicated by our study; diagnosis is often

  10. Atopic Dermatitis: Clinical Connotations, Especially a Focus on Concomitant Atopic Undertones in Immunocompromised/Susceptible Genetic and Metabolic Disorders.

    Science.gov (United States)

    Sehgal, Virendra N; Khurana, Ananta; Mendiratta, Vibhu; Saxena, Deepti; Srivastava, Govind; Aggarwal, Ashok K; Chatterjee, Kingshuk

    2016-01-01

    Atopic dermatitis (AD) is an intriguing clinical entity. Its clinical connotations are varied, the updates of which are required to be done periodically. An attempt to bring its various facets have been made highlighting its clinical features keeping in view the major and the minor criteria to facilitate the diagnosis, differential diagnosis, complications, and associated dermatoses. The benefit of the current dissertation may percolate to the trainees in dermatology, in addition to revelations that atopic undertones in genetic susceptibility and metabolic disorder may provide substantive insight for the future in the understanding of thus far enigmatic etiopathogenesis of AD. PMID:27293243

  11. Disorders of sex development: a genetic study of patients in a multidisciplinary clinic

    OpenAIRE

    Laino, Luigi; Majore, Silvia; Preziosi, Nicoletta; Grammatico, Barbara; De Bernardo, Carmelilia; Scommegna, Salvatore; Rapone, Anna Maria; Marrocco, Giacinto; Bottillo, Irene; Grammatico, Paola

    2014-01-01

    Sex development is a process under genetic control directing both the bi-potential gonads to become either a testis or an ovary, and the consequent differentiation of internal ducts and external genitalia. This complex series of events can be altered by a large number of genetic and non-genetic factors. Disorders of sex development (DSD) are all the medical conditions characterized by an atypical chromosomal, gonadal, or phenotypical sex. Incomplete knowledge of the genetic mechanisms involve...

  12. Proceedings of the international conference on radiation biology and clinical applications: a molecular approach towards innovations in applied radiobiology and a workshop on strategies in radiation research

    International Nuclear Information System (INIS)

    Innovations in radiotherapy approaches to cancer and radiation biology research is of growing interest in radiation researchers to conduct preclinical studies at their centers and translating the results as soon as possible to clinical radiotherapy practice. Recent papers have greatly enriched the current knowledge of radiation oncology, especially radiobiology and molecular oncology, and this has radically changed the oncology practice in radiation therapy in just a few years. The conference theme highlights the molecular and cellular responses within tissue and higher levels of mammalian biological organization. New experimental radiobiology research to underpin current and future regulatory decisions setting workplace exposure limits. To develop rapid, high-precision analytical methods that assess radiation exposure doses from clinical samples and thus aid in the triage and medical management of radiological casualties. Innovative approaches to improve the accuracy, dose range, ease of use, and speed of classical biodosimetry. Papers relevant to INIS are indexed separately

  13. Genetic diagnosis in clinical psychiatry: A case report of a woman with a 47, XXX karyotype and Fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Anthony M. Vandersteen

    2009-03-01

    Full Text Available Background and Objectives: A recent report highlighted the importance of considering a chromosomal abnormality in the differential diagnosis of adult clinical psychiatry. This case report illustrates the importance of considering Fragile X syndrome, an X-linked genetic disorder associated with psychiatric morbidities. Methods: A 45 years old woman was referred to the clinical genetics department by her psychiatrist for investigation of her gross obesity, hyperphagia, learning difficulties and affective disorder. Results: Cytogenetic analysis revealed a 47,XXX karyotype. Molecular testing identified an expansion of approximately 580 repeats in the FRAXA gene carried on two of her three copies of the X chromosome. Clinical evaluation revealed features consistent with the Prader-Willi like phenotype of Fragile X syndrome. Conclusions: It is important to consider molecular and cytogenetic testing in patients with dysmorphic features, complex neuro-behavioural profile and/or psychotic disorders in order to establish a causative diagnosis, provide adequate counselling and initiate cascade screening where applicable.

  14. Comparative analysis of Clostridium difficile clinical isolates belonging to different genetic lineages and time periods.

    Science.gov (United States)

    Spigaglia, Patrizia; Mastrantonio, Paola

    2004-11-01

    Recent studies have shown that Clostridium difficile strains with variant toxins and those with resistance to macrolide-lincosamide-streptogramin B (MLSB) are increasingly causing severe disease and outbreaks in hospital settings. Here, the pathogenicity locus (PaLoc), the acquisition of binary toxin, and the genotypic and phenotypic characteristics of antibiotic resistance of 74 C. difficile clinical strains isolated from symptomatic patients in Italy during different time periods were studied. These strains were found to belong to two different lineages, and those isolated before 1991 were genetically unrelated to the more recent strains. The majority of recent C. difficile strains showed variations in toxin genes and in the toxin negative regulator (tcdC) and had the binary toxin. In 62 % of them, variations in tcdC and the presence of the binary toxin were associated. Five classes of susceptibility/resistance pattern (EC-a to -e) for erythromycin and clindamycin were identified in all strains studied. Most of the recent isolates belonged to EC-d and EC-e and, although erythromycin-resistant in vitro, did not harbour the commonly associated ermB determinant. Interestingly, two strains of the EC-d class were resistant to clindamycin only after induction with subinhibitory concentrations of the antibiotic. A decrease in tetracycline and chloramphenicol MIC values was also observed in the recently isolated strains, associated with less frequent detection of the catD and tetM genes. Two tetM-positive strains were resistant in vitro only after induction with subinhibitory concentrations of the antibiotic. The acquisition of the binary toxin, the possible increase in toxin production due to a mutated negative regulator and a decrease in the fitness cost as a result of lower levels of antibiotic resistance or other mechanisms may have led to the successful establishment of these new phenotypes, with potentially serious clinical implications. PMID:15496392

  15. Clinical and genetic investigation of families with type II Waardenburg syndrome.

    Science.gov (United States)

    Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhou, Jianda; Zhu, Ganghua; Hu, Peng; Wu, Weijing

    2016-03-01

    The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia‑associated transcription factor (MITF), sex‑determining region Y‑box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease‑causing mutation in pedigree 1. However, there are novel disease‑causing genes in Waardenburg syndrome type II, which require further research. PMID:26781036

  16. HIV type 1 gag genetic diversity among antenatal clinic attendees in North Rift Valley, Kenya.

    Science.gov (United States)

    Nyagaka, Benuel; Kiptoo, Michael K; Lihana, Raphael W; Khamadi, Samoel A; Makokha, Ernest P; Kinyua, Joyceline G; Mwangi, Joseph; Osman, Saida; Lagat, Nancy J; Muriuki, Joseph; Okoth, Vincent; Gicheru, Michael; Ng'ang'a, Zipporah; Songok, Elijah M

    2012-05-01

    HIV genetic recombination and high mutation rate increase diversity allowing it to escape from host immune response or antiretroviral drugs. This diversity has enabled specific viral subtypes to be predominant in specific regions. To determine HIV-1 subtypes among seropositive antenatal clinic attendees in Kenya's North Rift Valley, a cross-sectional study was carried out on 116 HIV-1-positive blood samples. Proviral DNA was extracted from peripheral blood mononuclear cells by DNAzol lysis and ethanol precipitation. Polymerase chain reactions using specific primers for HIV-1 gag and population sequencing on resulting amplicons were carried out. Phylogenetic analysis revealed that 81 (70%) were subtype A1, 13 (11%) subtype D, 8 (7%) subtype C, 3 (3%) subtype A2, 1 (1%) subtype G, and 10 showed possible recombinants: 5 (4%) subtype A1D, 4 (3%) subtype A1C, and 1 (1%) subtype A2C. These data support the need to establish circulating subtypes for better evaluation of effective HIV diagnostic and treatment options in Kenya. PMID:21827277

  17. A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice

    Science.gov (United States)

    Sanchez-Alcudia, Rocio; Garcia-Hoyos, Maria; Lopez-Martinez, Miguel Angel; Sanchez-Bolivar, Noelia; Zurita, Olga; Gimenez, Ascension; Villaverde, Cristina; Rodrigues-Jacy da Silva, Luciana; Corton, Marta; Perez-Carro, Raquel; Torriano, Simona; Kalatzis, Vasiliki; Rivolta, Carlo; Avila-Fernandez, Almudena; Lorda, Isabel; Trujillo-Tiebas, Maria J.; Garcia-Sandoval, Blanca; Lopez-Molina, Maria Isabel; Blanco-Kelly, Fiona; Riveiro-Alvarez, Rosa; Ayuso, Carmen

    2016-01-01

    Choroideremia (CHM) is a rare X-linked disease leading to progressive retinal degeneration resulting in blindness. The disorder is caused by mutations in the CHM gene encoding REP-1 protein, an essential component of the Rab geranylgeranyltransferase (GGTase) complex. In the present study, we evaluated a multi-technique analysis algorithm to describe the mutational spectrum identified in a large cohort of cases and further correlate CHM variants with phenotypic characteristics and biochemical defects of choroideremia patients. Molecular genetic testing led to the characterization of 36 out of 45 unrelated CHM families (80%), allowing the clinical reclassification of four CHM families. Haplotype reconstruction showed independent origins for the recurrent p.Arg293* and p.Lys178Argfs*5 mutations, suggesting the presence of hotspots in CHM, as well as the identification of two different unrelated events involving exon 9 deletion. No certain genotype-phenotype correlation could be established. Furthermore, all the patients´ fibroblasts analyzed presented significantly increased levels of unprenylated Rabs proteins compared to control cells; however, this was not related to the genotype. This research demonstrates the major potential of the algorithm proposed for diagnosis. Our data enhance the importance of establish a differential diagnosis with other retinal dystrophies, supporting the idea of an underestimated prevalence of choroideremia. Moreover, they suggested that the severity of the disorder cannot be exclusively explained by the genotype. PMID:27070432

  18. Design of Clinical Support Systems Using Integrated Genetic Algorithm and Support Vector Machine

    Science.gov (United States)

    Chen, Yung-Fu; Huang, Yung-Fa; Jiang, Xiaoyi; Hsu, Yuan-Nian; Lin, Hsuan-Hung

    Clinical decision support system (CDSS) provides knowledge and specific information for clinicians to enhance diagnostic efficiency and improving healthcare quality. An appropriate CDSS can highly elevate patient safety, improve healthcare quality, and increase cost-effectiveness. Support vector machine (SVM) is believed to be superior to traditional statistical and neural network classifiers. However, it is critical to determine suitable combination of SVM parameters regarding classification performance. Genetic algorithm (GA) can find optimal solution within an acceptable time, and is faster than greedy algorithm with exhaustive searching strategy. By taking the advantage of GA in quickly selecting the salient features and adjusting SVM parameters, a method using integrated GA and SVM (IGS), which is different from the traditional method with GA used for feature selection and SVM for classification, was used to design CDSSs for prediction of successful ventilation weaning, diagnosis of patients with severe obstructive sleep apnea, and discrimination of different cell types form Pap smear. The results show that IGS is better than methods using SVM alone or linear discriminator.

  19. Genetic studies of DRD4 and clinical response to neuroleptic medications

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, J.L.; Petronis, A.; Gao, J. [Univ. of Toronto, Ontario (Canada)] [and others

    1994-09-01

    Clozapine is an atypical antipsychotic drug that, like most other medications, is effective for some people and not for others. This variable response across individuals is likely significantly determined by genetic factors. An important candidate gene to investigate in clozapine response is the dopamine D4 receptor gene (DRD4). The D4 receptor has a higher affinity for clozapine than any of the other dopamine receptors. Furthermore, recent work by our consortium has shown a remarkable level of variability in the part of the gene coding for the third cytoplasmic loop. We have also identified polymorphisms in the upstream 5{prime} putative regulatory region and at two other sites. These polymorphisms were typed in a group of treatment-resistant schizophrenia subjects who were subsequently placed on clozapine (n = 60). In a logistic regression analysis, we compared genotype at the DRD4 polymorphism to response versus non-response to clozapine. Neither the exon-III nor any of the 5{prime} polymorphisms alone significantly predicted response; however, when the information from these polymorphisms was combined, more predictive power was obtained. In a correspondence analysis of the four DRD4 polymorphisms vs. response, we were able to predict 76% of the variance in response. Refinement of the analyses will include assessment of subfactors involved in clinical response phenotype and incorporation of the debrisoquine metabolizing locus (CYP2D6) into the prediction algorithm.

  20. Update on Abdominal Aortic Aneurysm Research: From Clinical to Genetic Studies

    Directory of Open Access Journals (Sweden)

    Helena Kuivaniemi

    2014-01-01

    Full Text Available An abdominal aortic aneurysm (AAA is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person’s risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks.

  1. GLUT-1 DEFICIENCY: FROM PATHOPHYSILOGY AND GENETICS TO ABROAD CLINICAL SPECTRUM

    Directory of Open Access Journals (Sweden)

    Todor Arsov

    2016-07-01

    Full Text Available The classical GLUT-1 deficiency syndrome (GLUT-1 DS, De Vivo disease was described over 2 decades ago as a metabolic encephalopathy characterized by developmental delay, secondary microcephaly paroxysmal neurological symptoms (epilepsy and movement disorders. The biochemical parameters of this disease, used in diagnosis, are low levels of glucose in the cerebrospinal fluid, normal level of glucose in the blood and consequent low ratio of cerebrospinal fluid vs. blood glucose levels (<40-45%. So far, more than 200 cases of the classical GLUT-1 DS have been described in the literature. Genetic research demonstrated that this disease is caused by mutations in SLC2A1 gene coding for GLUT-1, a transporter of glucose across the blood brain barrier. Over the last few years the clinical spectrum of GLUT-1 deficiencywas expanded to include other rare diseases such as paroxysmal exertional dyskinesia and early-onset absence epilepsy, but also some more common diseases such as idiopathic generalised epilepsy (1-2%. GLUT-1 deficiency is an important pathophysiological basis of these diseases as early diagnosis (aided by DNA mutation testing and treatment (ketogenic diet could lead to improved disease outcomes.

  2. Clinical and genetic challenges in a family with history of childhood polyp, aortopathy, and clinical diagnosis of hereditary hemorrhagic teleangiectasia (HHT)

    Science.gov (United States)

    Kadiyska, Tanya; Nossikoff, Alexander; Kratunkov, Pencho; Hachmerian, Mary; Angelova, Ludmila

    2016-01-01

    Hereditary hemorrhagic teleangiectasia (HHT) is a genetic disorder, characterized by abnormal vessel formation and arteriovenous malformations (AVMs). The so-called “Curaçao criteria” are most commonly employed for the purposes of clinical diagnosis. However, children may not exhibit the full magnitude of symptoms and the Curaçao criteria appear to be less sensitive in this setting. We describe a family, in which two members were clinically diagnosed with HHT and referred for genetic testing. As there were phenotypic features suggesting the high likelihood of combined syndrome of juvenile polyposis with hereditary hemorrhagic teleangiectasia (JPHT), we proceeded with genetic testing of SMAD4 gene as initial step, which revealed a novel frameshift mutation. This case shows the variety of challenges that clinicians and genetic laboratories may face in complex cases such as combined JPHT syndrome. Knowledge of the syndrome features is of paramount importance as they could frequently point at the most appropriate gene to be tested. PMID:27212857

  3. 9. international mouse genome conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    This conference was held November 12--16, 1995 in Ann Arbor, Michigan. The purpose of this conference was to provide a multidisciplinary forum for exchange of state-of-the-art information on genetic mapping in mice. This report contains abstracts of presentations, focusing on the following areas: mutation identification; comparative mapping; informatics and complex traits; mutagenesis; gene identification and new technology; and genetic and physical mapping.

  4. International Conference on Rett Syndrome (4th, Vienna, Austria, October 2-5, 1986). Synopsis.

    Science.gov (United States)

    Percy, Alan

    Presentations from speakers at a conference on Rett Syndrome are summarized. The presentations focused on Rett Syndrome's genetic basis and identification as a clinical syndrome, involving, among other things, mental subnormality, epilepsy, infantile spasms, hand stereotypes, and poor hand use. Also discussed were: Rett Syndrome's predictive…

  5. Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.

    Science.gov (United States)

    Bente, Dennis A; Forrester, Naomi L; Watts, Douglas M; McAuley, Alexander J; Whitehouse, Chris A; Bray, Mike

    2013-10-01

    Crimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review

  6. Resistance Genes and Genetic Elements Associated with Antibiotic Resistance in Clinical and Commensal Isolates of Streptococcus salivarius.

    Science.gov (United States)

    Chaffanel, Fanny; Charron-Bourgoin, Florence; Libante, Virginie; Leblond-Bourget, Nathalie; Payot, Sophie

    2015-06-15

    The diversity of clinical (n = 92) and oral and digestive commensal (n = 120) isolates of Streptococcus salivarius was analyzed by multilocus sequence typing (MLST). No clustering of clinical or commensal strains can be observed in the phylogenetic tree. Selected strains (92 clinical and 46 commensal strains) were then examined for their susceptibilities to tetracyclines, macrolides, lincosamides, aminoglycosides, and phenicol antibiotics. The presence of resistance genes tet(M), tet(O), erm(A), erm(B), mef(A/E), and catQ and associated genetic elements was investigated by PCR, as was the genetic linkage of resistance genes. High rates of erythromycin and tetracycline resistance were observed among the strains. Clinical strains displayed either the erm(B) (macrolide-lincosamide-streptogramin B [MLSB] phenotype) or mef(A/E) (M phenotype) resistance determinant, whereas almost all the commensal strains harbored the mef(A/E) resistance gene, carried by a macrolide efflux genetic assembly (MEGA) element. A genetic linkage between a macrolide resistance gene and genes of Tn916 was detected in 23 clinical strains and 5 commensal strains, with a predominance of Tn3872 elements (n = 13), followed by Tn6002 (n = 11) and Tn2009 (n = 4) elements. Four strains harboring a mef(A/E) gene were also resistant to chloramphenicol and carried a catQ gene. Sequencing of the genome of one of these strains revealed that these genes colocalized on an IQ-like element, as already described for other viridans group streptococci. ICESt3-related elements were also detected in half of the isolates. This work highlights the potential role of S. salivarius in the spread of antibiotic resistance genes both in the oral sphere and in the gut. PMID:25862227

  7. Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity.

    Science.gov (United States)

    Garcia, John; Tahiliani, Jackie; Johnson, Nicole Marie; Aguilar, Sienna; Beltran, Daniel; Daly, Amy; Decker, Emily; Haverfield, Eden; Herrera, Blanca; Murillo, Laura; Nykamp, Keith; Topper, Scott

    2016-01-01

    Advances in DNA sequencing have made large, diagnostic gene panels affordable and efficient. Broad adoption of such panels has begun to deliver on the promises of personalized medicine, but has also brought new challenges such as the presence of unexpected results, or results of uncertain clinical significance. Genetic analysis of inherited cardiac conditions is particularly challenging due to the extensive genetic heterogeneity underlying cardiac phenotypes, and the overlapping, variable, and incompletely penetrant nature of their clinical presentations. The design of effective diagnostic tests and the effective use of the results depend on a clear understanding of the relationship between each gene and each considered condition. To address these issues, we developed simple, systematic approaches to three fundamental challenges: (1) evaluating the strength of the evidence suggesting that a particular condition is caused by pathogenic variants in a particular gene, (2) evaluating whether unusual genotype/phenotype observations represent a plausible expansion of clinical phenotype associated with a gene, and (3) establishing a molecular diagnostic strategy to capture overlapping clinical presentations. These approaches focus on the systematic evaluation of the pathogenicity of variants identified in clinically affected individuals, and the natural history of disease in those individuals. Here, we applied these approaches to the evaluation of more than 100 genes reported to be associated with inherited cardiomyopathies and arrhythmias including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia or cardiomyopathy, long QT syndrome, short QT syndrome, Brugada, and catecholaminergic polymorphic ventricular tachycardia, and to a set of related syndromes such as Noonan Syndrome and Fabry disease. These approaches provide a framework for delivering meaningful and accurate genetic test results to individuals with hereditary

  8. Re-conceptualizing risk in genetic counseling: implications for clinical practice

    OpenAIRE

    Austin, Jehannine C.

    2010-01-01

    Risk communication is an important component of genetic counseling. However, many authors have noted that after genetic counseling, subjective risk frequently does not match the objective risk provided by the counselor. This inevitably leads to the conclusion that the risk communication process was not “effective”. There has been much discussion about how this problem can be better addressed, such that our clients recall numeric risks more accurately after genetic counseling. This article dra...

  9. GENetic and clinical Predictors Of treatment response in Depression: the GenPod randomised trial protocol

    Directory of Open Access Journals (Sweden)

    O'Donovan Michael

    2008-05-01

    Full Text Available Abstract Background The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin (Selective Serotonin Reuptake Inhibitors – SSRIs and noradrenaline (Noradrenaline Reuptake Inhibitors – NaRIs into the presynaptic terminal. There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action. Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs, there are patients who respond to one class of compounds and not another. This suggests that treatment response could be predicted by genetic and/or clinical characteristics. Firstly, this study aims to investigate the influence of a polymorphism (SLC6A4 in the 5HT transporter in altering response to SSRI medication. Secondly, the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs. Methods/design The GenPod trial is a multi-centre randomised controlled trial. GPs referred patients aged between 18–74 years presenting with a new episode of depression, who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse. Patients were interviewed to ascertain their suitability for the study. Eligible participants (with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory (BDI score > 14 were randomised to receive one of two antidepressant treatments, either the SSRI Citalopram or the NaRI Reboxetine, stratified according to severity. The final number randomised to the trial was 601. Follow-up assessments took place at 2, 6 and 12 weeks following randomisation. Primary outcome was measured at 6 weeks by the BDI. Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments

  10. Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence.

    LENUS (Irish Health Repository)

    Murphy, S

    2012-02-01

    BACKGROUND: Cognitive impairment and dementia has been reported in autosomal dominant hereditary spastic paraparesis (HSP) linked to the SPG4 locus. There has only been one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder. OBJECTIVE: A family with SPG4-HSP known to have a deletion of exon 17 in the spastin gene (SPG4delEx17) was cognitively assessed over a 7-year period. The index family member died and a postmortem examination was performed. METHODS: Thirteen family members older than 40 years were clinically and cognitively assessed using the Cambridge Cognitive Assessment over a 7-year period. The presence of SPG4delEx17 was assessed; a neuropathologic examination of the brain of the index family member was performed. RESULTS: Cognitive decline occurred in 6 of the 13 family members and in all 4 older than 60 years. Two genetic deletions were identified: SPG4delEx17 in 12 of the 13 family members and a deletion of SPG6 (SPG6del) in 5. Eight individuals had the SPG4delEx17 deletion only; 4 had evidence of progressive cognitive impairment. Four family members had both SPG4delEx17 and SPG6del; 2 of these had cognitive impairment. One family member with the SPG6del alone had neither HSP nor cognitive impairment. The index case with both deletions died with dementia; the brain showed widespread ubiquitin positivity within the neocortex and white matter. CONCLUSION: Cognitive decline and dementia is a feature of SPG4-HSP due to a deletion of exon 17 of the spastin gene.

  11. Frontotemporal Dementia: Genetics

    Science.gov (United States)

    ... Calendar of Events Fundraising Events Conferences Press Releases Genetics of FTD After receiving a diagnosis of FTD ... that recent advances in science have brought the genetics of FTD into much better focus. In 2012, ...

  12. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Irving, Julie A E; Enshaei, Amir; Parker, Catriona A; Sutton, Rosemary; Kuiper, Roland P; Erhorn, Amy; Minto, Lynne; Venn, Nicola C; Law, Tamara; Yu, Jiangyan; Schwab, Claire; Davies, Rosanna; Matheson, Elizabeth; Davies, Alysia; Sonneveld, Edwin; den Boer, Monique L; Love, Sharon B; Harrison, Christine J; Hoogerbrugge, Peter M; Revesz, Tamas; Saha, Vaskar; Moorman, Anthony V

    2016-08-18

    Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also we screened 238 patients with a marrow relapse for selected copy number alterations (CNAs) and mutations. Cytogenetic risk groups were predictive of outcome postrelapse and survival rates at 5 years for patients with good, intermediate-, and high-risk cytogenetics were 68%, 47%, and 26%, respectively (P www.clinicaltrials.org as #ISCRTN45724312. PMID:27229005

  13. Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency

    Directory of Open Access Journals (Sweden)

    Djidjik Réda

    2012-08-01

    Full Text Available Abstract Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26. Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

  14. Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis

    OpenAIRE

    JAMIESON, S.E.; de Roubaix, L. A.; Cortina-Borja, M.; Tan, H K; Mui, E. J.; Cordell, H J; Kirisits, M. J.; Miller, E. N.; Peacock, C. S.; Hargrave, A. C.; Coyne, J J; Boyer, K.; Bessieres, M H; Buffolano, W.; Ferret, N

    2008-01-01

    Background: Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may ...

  15. Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity

    OpenAIRE

    Conway, Christopher C.; Slavich, George M.; Hammen, Constance

    2014-01-01

    Despite decades of research examining diathesis-stress models of emotional disorders, it remains unclear whether dysfunctional attitudes interact with stressful experiences to shape affect on a daily basis and, if so, how clinical and genetic factors influence these associations. To address these issues, we conducted a multi-level daily diary study that examined how dysfunctional attitudes and stressful events relate to daily fluctuations in negative and positive affect in 1...

  16. Population Genetic Structure of Clinical and Environmental Isolates of Blastomyces dermatitidis, Based on 27 Polymorphic Microsatellite Markers ▿ †

    OpenAIRE

    Meece, Jennifer K.; Anderson, Jennifer L.; Fisher, Matthew C; Henk, Daniel A.; Sloss, Brian L; Reed, Kurt D.

    2011-01-01

    Blastomyces dermatitidis, a thermally dimorphic fungus, is the etiologic agent of North American blastomycosis. Clinical presentation is varied, ranging from silent infections to fulminant respiratory disease and dissemination to skin and other sites. Exploration of the population genetic structure of B. dermatitidis would improve our knowledge regarding variation in virulence phenotypes, geographic distribution, and difference in host specificity. The objective of this study was to develop a...

  17. An epidemiological, clinical and genetic survey of Neurofibromatosis type 1 in children under sixteen years of age

    OpenAIRE

    McKeever, Karl; Shepherd, Charles W; Crawford, Hilda; Morrison, Patrick J.

    2008-01-01

    Aim To identify all cases of Neurofibromatosis type 1 in Northern Ireland under 16 years of age, document age, modes of presentation and any complications that occurred. Methods All cases of Neurofibromatosis type 1 in children less than 16 years of age were identified from the records in the Department of Medical Genetics. From the records and by direct contact with the patient's parents the relevant clinical information was obtained. Results Seventy-five children aged sixteen years or less ...

  18. Next Generation Sequencing in the Clinic: a Patterns of Care Study in a Retrospective Cohort of Subjects Referred to a Genetic Medicine Clinic for Suspected Lynch Syndrome.

    Science.gov (United States)

    Gallego, Carlos J; Perez, Matthew L; Burt, Amber; Amendola, Laura M; Shirts, Brian H; Pritchard, Colin C; Hisama, Fuki M; Bennett, Robin L; Veenstra, David L; Jarvik, Gail P

    2016-06-01

    Next generation sequencing (NGS) gene panels are increasingly used in medical genetics clinics for the evaluation of common inherited cancer syndromes, but the clinical efficacy of these tests, and the factors driving clinical providers to order them are unclear. We conducted a patterns-of-care study to compare patients evaluated with NGS gene panels with a reference group. We abstracted demographic, socioeconomic, and clinical information in a retrospective cohort of patients referred to a large medical genetics clinic for evaluation of inherited colorectal cancer and polyposis syndromes. Patients tested with NGS gene panels were more likely to be insured compared to the reference group (85.3 % vs. 69.2 %, p = 0.0068),less likely to have prior tumor tissue testing (29.4 % vs. 54.3 %, p = 0.0004), and less likely to have an abnormal tumor tissue test result (46.7 % vs. 74.5 %, p = 0.01). No significant differences were found between groups in age, gender, race, employment status, personal history of colorectal cancer, or proportion of patients fulfilling Lynch syndrome clinical criteria. Patients with NGS testing were less likely to have a pathogenic/likely pathogenic variant detected (13.7 % vs. 31.9 %, p = 0.002). Patients referred for NGS testing to evaluate inherited colorectal cancer/polyposis risk appear to undergo tumor tissue testing less frequently than non-NGS testing patients. Further studies are needed to assess the most effective and cost-effective approach to genomic diagnosis in this patient population. PMID:26637299

  19. Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

    Czech Academy of Sciences Publication Activity Database

    Alonso-Perez, E.; Suarez-Gestal, M.; Calaza, M.; Witte, T.; Papasteriades, Ch.; Marchini, M.; Migliaresi, S.; Kovacs, A.; Ordi-Ros, J.; Bijl, M.; Santos, M.J.; Růžičková, Šárka; Pullmann, R.; Carreira, P.; Skopouli, F.N.; D'Alfonso, S.; Sebastiani, G.D.; Suarez, A.; Blanco, F.J.; Gomez-Reino, J.J.; Gonzalez, A.

    2012-01-01

    Roč. 6, č. 12 (2012), e29033. E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z50520701 Keywords : erythematosus * genetic factors * genotype phenotype correlation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2012

  20. [Genetics and genetic counseling].

    Science.gov (United States)

    Izzi, Claudia; Liut, Francesca; Dallera, Nadia; Mazza, Cinzia; Magistroni, Riccardo; Savoldi, Gianfranco; Scolari, Francesco

    2016-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic disease, characterized by progressive development of bilateral renal cysts. Two causative genes have been identified: PKD1 and PKD2. ADPKD phenotype is highly variable. Typically, ADPKD is an adult onset disease. However, occasionally, ADPKD manifests as very early onset disease. The phenotypic variability of ADPKD can be explained at three genetic levels: genic, allelic and gene modifier effects. Recent advances in molecular screening for PKD gene mutations and the introduction of the new next generation sequencing (NGS)- based genotyping approach have generated considerable improvement regarding the knowledge of genetic basis of ADPKD. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, focusing on new insights in genotype-phenotype correlation and exploring novel clinical approach to genetic testing. Evaluation of these new genetic information requires a multidisciplinary approach involving a nephrologist and a clinical geneticist. PMID:27067213

  1. When research seems like clinical care: a qualitative study of the communication of individual cancer genetic research results

    Directory of Open Access Journals (Sweden)

    Robert Jason S

    2008-02-01

    Full Text Available Abstract Background Research ethicists have recently declared a new ethical imperative: that researchers should communicate the results of research to participants. For some analysts, the obligation is restricted to the communication of the general findings or conclusions of the study. However, other analysts extend the obligation to the disclosure of individual research results, especially where these results are perceived to have clinical relevance. Several scholars have advanced cogent critiques of the putative obligation to disclose individual research results. They question whether ethical goals are served by disclosure or violated by non-disclosure, and whether the communication of research results respects ethically salient differences between research practices and clinical care. Empirical data on these questions are limited. Available evidence suggests, on the one hand, growing support for disclosure, and on the other, the potential for significant harm. Methods This paper explores the implications of the disclosure of individual research results for the relationship between research and clinical care through analysis of research-based cancer genetic testing in Ontario, Canada in the late 1990s. We analyze a set of 30 interviews with key informants involved with research-based cancer genetic testing before the publicly funded clinical service became available in 2000. Results We advance three insights: First, the communication of individual research results makes research practices seem like clinical services for our respondents. Second, while valuing the way in which research enables a form of clinical access, our respondents experience these quasi-clinical services as inadequate. Finally, our respondents recognize the ways in which their experience with these quasi-clinical services is influenced by research imperatives, but understand and interpret the significance and appropriateness of these influences in different ways. Conclusion

  2. Risk assessment models in genetics clinic for array comparative genomic hybridization: Clinical information can be used to predict the likelihood of an abnormal result in patients

    Science.gov (United States)

    Marano, Rachel M.; Mercurio, Laura; Kanter, Rebecca; Doyle, Richard; Abuelo, Dianne; Morrow, Eric M.; Shur, Natasha

    2013-01-01

    Array comparative genomic hybridization (aCGH) testing can diagnose chromosomal microdeletions and duplications too small to be detected by conventional cytogenetic techniques. We need to consider which patients are more likely to receive a diagnosis from aCGH testing versus patients that have lower likelihood and may benefit from broader genome wide scanning. We retrospectively reviewed charts of a population of 200 patients, 117 boys and 83 girls, who underwent aCGH testing in Genetics Clinic at Rhode Island hospital between 1 January/2008 and 31 December 2010. Data collected included sex, age at initial clinical presentation, aCGH result, history of seizures, autism, dysmorphic features, global developmental delay/intellectual disability, hypotonia and failure to thrive. aCGH analysis revealed abnormal results in 34 (17%) and variants of unknown significance in 24 (12%). Patients with three or more clinical diagnoses had a 25.0% incidence of abnormal aCGH findings, while patients with two or fewer clinical diagnoses had a 12.5% incidence of abnormal aCGH findings. Currently, we provide families with a range of 10–30% of a diagnosis with aCGH testing. With increased clinical complexity, patients have an increased probability of having an abnormal aCGH result. With this, we can provide individualized risk estimates for each patient.

  3. A systematic approach to assessing the clinical significance of genetic variants

    OpenAIRE

    Duzkale, H; Shen, J; McLaughlin, H; Alfares, A; Kelly, MA; Pugh, TJ; Funke, BH; Rehm, HL; Lebo, MS

    2013-01-01

    Molecular genetic testing informs diagnosis, prognosis, and risk assessment for patients and their family members. Recent advances in low-cost, high-throughput DNA sequencing and computing technologies have enabled the rapid expansion of genetic test content, resulting in dramatically increased numbers of DNA variants identified per test. To address this challenge, our laboratory has developed a systematic approach to thorough and efficient assessments of variants for pathogenicity determinat...

  4. Familial disorders of sexual differentiation: a clinical and molecular genetic evaluation

    OpenAIRE

    Boehmer, Annemie

    2000-01-01

    textabstractSexual determination and differentiation are series of events starting with the establishment of genetic sex at fertilization, proceeding with the translation of genetic sex into gonadal sex, and culminating in the translation of gonadal sex into body sex. This three-step model is still valid, but actually (2000) much more complex. Many factors involved in normal sexual determination and differentiation became known, were cloned or defined on the molecular level during recent year...

  5. A clinical appraisal of the genetic basis in unexplained male infertility

    Directory of Open Access Journals (Sweden)

    Sandro C Esteves

    2013-01-01

    Full Text Available Unexplained male infertility (UMI, the inability to reproduce despite having a normal sexual history, physical exam and semen analysis, can have a genetic origin. Currently, few diagnostic tools are available for detecting such genetic abnormalities. Karyotyping and fluorescence in situ hybridization (FISH are respectively used for chromosomal alterations in somatic cells and sperm aneuploidy assessment. Gene sequencing and mutational analysis have been introduced for identifying specific mutations and polymorphisms. Other approaches to the molecular evaluation of spermatozoa are under investigation, including array comparative genomic hybridization and whole-genome sequencing and non-coding ribonucleic acid arrays. Although treating cytogenetic abnormalities and genetic aberrations is still out of reach, the integration of these novel techniques may unravel hidden genetic defects in UMI. Finally, a deeper understanding of the sperm epigenome might allow the development of therapies based on epigenome modifications. This review focuses on the genetic basis of UMI and highlights the current and future methods for the evaluation of genetic defects as they relate to UMI. Review of the literature was carried out using ScienceDirect, OVID, PubMed and MedLine search engines.

  6. A novel 1050nm handheld OCT imaging system for pediatric retinoblastoma patients: technology development and clinical study (Conference Presentation)

    Science.gov (United States)

    Nadiarnykh, Oleg; Moll, Annette C.; de Boer, Johannes F.

    2016-03-01

    We demonstrate a novel optical coherence tomography system specifically developed and validated for clinical imaging of retinoblastoma tumors in pediatric patients. The existing treatment options for this malignant tumor of the retina aim at reduction of tumor (re)growth risks, and vision preservation. The choice of optimal treatment strongly depends on skilled and detailed clinical assessment. Due to the limitations of the existing real-time diagnostic tools the patients at risk are periodically monitored with retinal imaging to confirm the absence of new tumor seedings. Three-dimensional visualization of tissue layer and microvasculature at improved axial and lateral resolution of interference-based OCT imaging provides sensitivity for detection of vital tumor tissue concurrent with local treatment. Our METC-approved system accommodates for the range of optical parameters of infants' eyes, and uses the 1050nm wavelength to access the deeper choroid layers of retina. The prototype is designed for patients in supine position under general anesthesia, where ergonomic handheld module is connected to fiber-based optical setup via umbilical cord. The system conforms to clinical safety requirements, including fully isolated low-voltage electric circuit. Focusing is performed with a mechanically tunable lens, where resolution is 6 µm axially, and varies with focusing at 10-18µm laterally. We will present optical design, performance limitations, and results of the ongoing clinical study, including the increased OCT diagnostic sensitivity in three dimensions in comparison with the established clinical imaging modalities. We will discuss images of early, active, and treated tumors, as well as follow-up on patients after local and systemic treatments.

  7. Closing the loop: an interactive action-research conference format for delivering updated medical information while eliciting Latina patient/family experiences and psychosocial needs post-genetic cancer risk assessment.

    Science.gov (United States)

    Macdonald, Deborah J; Deri, Julia; Ricker, Charité; Perez, Martin A; Ogaz, Raquel; Feldman, Nancy; Viveros, Lori A; Paz, Benjamin; Weitzel, Jeffrey N; Blazer, Kathleen R

    2012-09-01

    A patient/family-centered conference was conducted at an underserved community hospital to address Latinas' post-genetic cancer risk assessment (GCRA) medical information and psychosocial support needs, and determine the utility of the action research format. Latinas seen for GCRA were recruited to a half-day conference conducted in Spanish. Content was partly determined from follow-up survey feedback. Written surveys, interactive discussions, and Audience Response System (ARS) queries facilitated the participant-healthcare professional action research process. Analyses included descriptive statistics and thematic analysis. The 71 attendees (41 patients and 27 relatives/friends) were primarily non-US born Spanish-speaking females, mean age 43 years. Among patients, 73 % had a breast cancer history; 85 % had BRCA testing (49 % BRCA+). Nearly all (96 %) attendees completed the conference surveys and ARS queries; ≥48 % participated in interactive discussions. Most (95 %) agreed that the format met their personal interests and expectations and provided useful information and resources. Gaps/challenges identified in the GCRA process included pre-consult anxiety, uncertainty about reason for referral and expected outcomes, and psychosocial needs post-GCRA, such as absorbing and disseminating risk information to relatives and concurrently coping with a recent cancer diagnosis. The combined action research and educational conference format was innovative and effective for responding to continued patient information needs and addressing an important data gap about support needs of Latina patients and family members following genetic cancer risk assessment. Findings informed GCRA process improvements and provide a basis for theory-driven cancer control research. PMID:22678665

  8. Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. Yet Active immunization using genetically modified dendritic cells holds promise for the adjuvant treatment of malignancies to eradicate or control residual disease. Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD8+ T cells with diverse TCR specificities, possessing non-MHC-restricted cytolytic activities against tumor cells. Clinical studies have confirmed benefit and safety of CIK cell-based therapy for patients with malignancies. This clinical trial was conducted to evaluate efficacy and safety of genetically modified dendritic cells in combination with Cytokine-Induced Killer Cell (gmDCs-CIK) treatment of patients with RCC. 28 patients with advanced renal cancer were admitted to Affiliated Hospital of Academy of Military Medical Sciences from December 2010 to March 2012 and treated by gmDCs-CIK. Clinical efficacy and safety between pre- and post-treatment were compared. This analysis showed an objective response rate (ORR) of 39% and a disease control rate (DCR) of as 75%. There is no significant relationship between clinical efficacy and whether metastasis occurred or not (P > 0.05). There is no significant relationship between ORR and cycles of treatment (P > 0.05), but DCR was significantly related with cycles of treatment (P < 0.05). No clinically significant side effects were observed. There were no significant changes of T cell subsets including CD3+, CD4+, CD8+, CD4+ CD25+ Treg cells except Th1 in peripheral blood between day 30 after immunotherapy and 1 day before immunotherapy in 11 patients. DC-CIK is feasible and effective in treating advanced renal cancer and thus provides a new approach. ClinicalTrials.gov Identifier: http://clinicaltrials.gov/ct2/show/NCT01924156. Registration date: August 14, 2013

  9. Genetic modifiers of sickle cell anemia in the BABY HUG cohort: influence on laboratory and clinical phenotypes.

    Science.gov (United States)

    Sheehan, Vivien A; Luo, Zhaoyu; Flanagan, Jonathan M; Howard, Thad A; Thompson, Bruce W; Wang, Winfred C; Kutlar, Abdullah; Ware, Russell E

    2013-07-01

    The recently completed BABY HUG trial investigated the safety and efficacy of hydroxyurea in infants with sickle cell anemia (SCA). To investigate the effects of known genetic modifiers, genomic DNA on 190 randomized subjects were analyzed for alpha thalassemia, beta-globin haplotype, polymorphisms affecting endogenous fetal hemoglobin (HbF) levels (XmnI, BCL11A, and HBS1L-MYB), UGT1A1 promoter polymorphisms, and the common G6PD A(-) mutation. At study entry, infants with alpha thalassemia trait had significantly lower mean corpuscular volume, total bilirubin, and absolute reticulocyte count. Beta-globin haplotypes associated with milder disease had significantly higher hemoglobin and %HbF. BCL11A and XmnI polymorphisms had significant effects on baseline HbF, while UGT1A1 promoter polymorphisms significantly influenced baseline serum bilirubin. At study exit, subjects randomized to placebo still exhibited laboratory effects of alpha thalassemia and other modifiers, while those assigned hydroxyurea had treatment effects that exceeded most genetic influences. The pain phenotype was influenced by HbF modifiers in both treatment groups. These data document that genetic polymorphisms do modify laboratory and clinical phenotypes even in very young patients with SCA. The hydroxyurea effects are more potent, however, indicating that treatment criteria should not be limited to certain genetic subsets, and supporting the use of hydroxyurea for all young patients with SCA. PMID:23606168

  10. Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know.

    Science.gov (United States)

    Schuurman, Agnes G; van der Kolk, Dorina M; Verkerk, Marian A; Birnie, Erwin; Ranchor, Adelita V; Plantinga, Mirjam; van Langen, Irene M

    2015-09-01

    We explored the dilemma between patients' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation. At the moment, only a small number of patients are involved; however, the expanding possibilities for genetic risk profiling means this issue must be addressed because of potentially adverse societal and financial impact. The trade-off between patients' right not to know their genetic status and efficient use of health-care resources was discussed in six focus groups with health-care professionals and patients from three Dutch university hospitals. Professionals prefer patients to undergo a predictive DNA test as a prerequisite for entering cancer screening programmes. Professionals prioritise treating sick patients or proven mutation carriers over screening untested individuals. Participation in cancer screening programmes without prior DNA testing is, however, supported by most professionals, as testing is usually delayed and relatively few patients are involved at present. Reducing the number of 50% risk carriers undergoing screening is expected to be achieved by: offering more psychosocial support, explaining the iatrogenic risks of cancer screening, increasing out-of-pocket costs, and offering a less stringent screening programme for 50% risk carriers. PMID:25564039

  11. Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know

    Science.gov (United States)

    Schuurman, Agnes G; van der Kolk, Dorina M; Verkerk, Marian A; Birnie, Erwin; Ranchor, Adelita V; Plantinga, Mirjam; van Langen, Irene M

    2015-01-01

    We explored the dilemma between patients' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation. At the moment, only a small number of patients are involved; however, the expanding possibilities for genetic risk profiling means this issue must be addressed because of potentially adverse societal and financial impact. The trade-off between patients' right not to know their genetic status and efficient use of health-care resources was discussed in six focus groups with health-care professionals and patients from three Dutch university hospitals. Professionals prefer patients to undergo a predictive DNA test as a prerequisite for entering cancer screening programmes. Professionals prioritise treating sick patients or proven mutation carriers over screening untested individuals. Participation in cancer screening programmes without prior DNA testing is, however, supported by most professionals, as testing is usually delayed and relatively few patients are involved at present. Reducing the number of 50% risk carriers undergoing screening is expected to be achieved by: offering more psychosocial support, explaining the iatrogenic risks of cancer screening, increasing out-of-pocket costs, and offering a less stringent screening programme for 50% risk carriers. PMID:25564039

  12. Conference summaries

    International Nuclear Information System (INIS)

    This volume contains conference summaries for the 31. annual conference of the Canadian Nuclear Association and the 12. annual conference of the Canadian Nuclear Society. Topics of discussion include: reactor physics; thermalhydraulics; industrial irradiation; computer applications; fuel channel analysis; small reactors; severe accidents; fuel behaviour under accident conditions; reactor components, safety related computer software; nuclear fuel management; fuel behaviour and performance; reactor safety; reactor engineering; nuclear waste management; and, uranium mining and processing

  13. Nostradamus conference

    CERN Document Server

    Rössler, Otto; Snášel, Václav; Abraham, Ajith; Corchado, Emilio; Nostradamus: Modern Methods of Prediction, Modeling and Analysis of Nonlinear Systems

    2013-01-01

    This proceeding book of Nostradamus conference (http://nostradamus-conference.org) contains accepted papers presented at this event in 2012. Nostradamus conference was held in the one of the biggest and historic city of Ostrava (the Czech Republic, http://www.ostrava.cz/en), in September 2012. Conference topics are focused on classical as well as modern methods for prediction of dynamical systems with applications in science, engineering and economy. Topics are (but not limited to): prediction by classical and novel methods, predictive control, deterministic chaos and its control, complex systems, modelling and prediction of its dynamics and much more.

  14. Danish retinoblastoma patients 1943-2013 - genetic testing and clinical implications

    DEFF Research Database (Denmark)

    Gregersen, Pernille A; Urbak, Steen F; Funding, Mikkel;

    2015-01-01

    of patients diagnosed before DNA testing was offered. Knowledge of heredity increases the chance of early diagnosis in offspring, leading to improved prognosis. We present data from the Danish retinoblastoma patients that emphasize the need for genetic counseling and RB1 screening in all untested......, the rate has been stable around 1 per 14 000 live births with 95% of the patients surviving their retinoblastoma. Stratifying data on the time of diagnosis and status of genetic testing, the number of screened patients gradually increased from 5% in the beginning of the period to 96% in the last five......-year period. A cohort of 181 retinoblastoma survivors with sporadic disease (15% heritable) did not receive genetic testing. Since the introduction of routine testing, one of 14 sporadic unilateral patients tested (7%) has been identified with a germline mutation. Before routine testing, five additional...

  15. Clinical and Genetic Characteristics of Mexican Patients with Juvenile Presentation of Niemann-Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Raul E. Piña-Aguilar

    2014-01-01

    Full Text Available Niemann-Pick type C disease (NPC is a rare lysosomal disease with a protean presentation, ranging from a fatal neonatal course with visceromegaly to an adult presentation with only neurological or psychiatric symptomatology. In this report we describe the genetic and clinical characteristics of 3 Mexican patients from different families with juvenile presentation of NPC. Clinical examination, imaging of central nervous and gastrointestinal system, and EEG were performed. Genetic studies include sequencing and deletion/duplication analysis of NPC1 and NPC2 genes. All patients presented with cognitive impairment, ataxia, and supranuclear vertical gaze palsy; one case had gelastic cataplexy. Also they developed epilepsy and cortical atrophy and two patients had thinning of corpus callosum. The 3 patients were compound heterozygotes for NPC1 sequence variants, including 5 missense and 1 nonsense mutations: p.P1007A and p.F1087L in Case 1; p.Q921P and p.G992R in Case 2; and p.R348* and p.V1165M in case 3. Mexican patients with juvenile NPC presented with a variable clinical phenotype and compound heterozygosity. This suggests a relative high frequency of mutation carriers as it is reported for European population. Consequently, clinicians should consider NPC as a diagnosis possibility in any adolescent or young adult patient with juvenile dementia and/or ataxia, even in absence of gelastic cataplexy and supranuclear vertical gaze palsy.

  16. Discrepancy in compliance between the clinical and genetic diagnosis of choroidal hypoplasia in Danish Rough Collies and Shetland Sheepdogs.

    Science.gov (United States)

    Fredholm, M; Larsen, R C; Jönsson, M; Söderlund, M A; Hardon, T; Proschowsky, H F

    2016-04-01

    Collie eye anomaly (CEA) is a congenital, inherited ocular disorder which is widespread in herding breeds. Clinically, the two major lesions associated with CEA are choroidal hypoplasia (CH) and coloboma, and both lesions are diagnosed based on ophthalmological examination. A 7.8-kb intronic deletion in the gene encoding non-homologous end-joining factor 1 (NHEJ1) has been reported to be the causative mutation underlying CH when present in the homozygous state. In this study, we have investigated the compliance between the clinical and genetic diagnosis of CH in the Danish Rough Collie and Shetland Sheepdog populations. Our results show that the deletion in NHEJ1 is not predictive for CH in the Danish Rough Collie population, whereas the clinical and genetic diagnosis is in accordance with each other in the Shetland Sheepdog population. Based on these results, it can be concluded that the intronic deletion in NHEJ1 is not the causative mutation but, rather, a marker linked to the locus underlying the trait in some populations but linked to both the wild-type and CH-causing locus in most dogs in the Danish Rough Collie population. PMID:26732749

  17. Comparison of Enterococcus faecium and Enterococcus faecalis Strains isolated from water and clinical samples: antimicrobial susceptibility and genetic relationships.

    Directory of Open Access Journals (Sweden)

    Gonzalo Castillo-Rojas

    Full Text Available Enterococci are part of the normal intestinal flora in a large number of mammals, and these microbes are currently used as indicators of fecal contamination in water and food for human consumption. These organisms are considered one of the primary causes of nosocomial and environmental infections due to their ability to survive in the environment and to their intrinsic resistance to antimicrobials. The aims of this study were to determine the biochemical patterns and antimicrobial susceptibilities of Enterococcus faecalis and E. faecium isolates from clinical samples and from water (groundwater, water from the Xochimilco wetland, and treated water from the Mexico City Metropolitan Area and to determine the genetic relationships among these isolates. A total of 121 enterococcus strains were studied; 31 and 90 strains were isolated from clinical samples and water (groundwater, water from the Xochimilco wetland, and water for agricultural irrigation, respectively. Identification to the species level was performed using a multiplex PCR assay, and antimicrobial profiles were obtained using a commercial kit. Twenty-eight strains were analyzed by pulsed-field gel electrophoresis (PFGE. E. faecium strains isolated from water showed an atypical biochemical pattern. The clinical isolates showed higher resistance to antibiotics than those from water. Both the enterococci isolated from humans, and those isolated from water showed high genetic diversity according to the PFGE analysis, although some strains seemed to be closely related. In conclusion, enterococci isolated from humans and water are genetically different. However, water represents a potential route of transmission to the community and a source of antimicrobial resistance genes that may be readily transmitted to other, different bacterial species.

  18. Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

    OpenAIRE

    van den Broek, Alexandra J.; de Ruiter, Karen; Van 't Veer, Laura J; Tollenaar, Rob A.E.M.; van Leeuwen, Flora E.; Verhoef, Senno; Schmidt, Marjanka K.

    2014-01-01

    In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974–2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA...

  19. Genetic parameters of pathogen-specific incidence of clinical mastitis in dairy cows

    NARCIS (Netherlands)

    Haas, de Y.; Barkema, H.W.; Veerkamp, R.F.

    2002-01-01

    The objective of this study was to estimate heritabilities for and genetic correlations among different pathogen-specific mastitis traits. The traits were unspecific mastitis, which is all mastitis treatments regardless of the causative pathogen as well as mastitis caused by Streptococcus dysgalacti

  20. Genetic diversity of Trichomonas vaginalis clinical isolates from Henan province in central China.

    Science.gov (United States)

    Mao, Meng; Liu, Hui Li

    2015-07-01

    Trichomonas vaginalis is a flagellated protozoan parasite that infects the human urogenital tract, causing the most common non-viral, sexually transmitted disease worldwide. In this study, genetic variants of T. vaginalis were identified in Henan Province, China. Fragments of the small subunit of nuclear ribosomal RNA (18S rRNA) were amplified from 32 T. vaginalis isolates obtained from seven regions of Henan Province. Overall, 18 haplotypes were determined from the 18S rRNA sequences. Each sampled population and the total population displayed high haplotype diversity (Hd), accompanied by very low nucleotide diversity (Pi). In these molecular genetic variants, 91.58% genetic variation was derived from intra-regions. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. Demographic analysis supported population expansion of T. vaginalis isolates from central China. Our findings showing moderate-to-high genetic variations in the 32 isolates of T. vaginalis provide useful knowledge for monitoring changes in parasite populations for the development of future control strategies. PMID:26103990

  1. Conference summaries

    International Nuclear Information System (INIS)

    This volume contains conference summaries of the international conference on radioactive waste management of the Canadian Nuclear Society. Topics of discussion include: storage and disposal; hydrogeology and geochemistry; transportation; buffers and backfill; public attitudes; tailings; site investigations and geomechanics; concrete; economics; licensing; matrix materials and container design; durability of fuel; biosphere modelling; radioactive waste processing; and, future options

  2. A standardized framework for the validation and verification of clinical molecular genetic tests.

    NARCIS (Netherlands)

    Mattocks, C.J.; Morris, M.A.; Matthijs, G.; Swinnen, E.; Corveleyn, A.; Dequeker, E.; Muller, C.R.; Pratt, V.; Wallace, A.

    2010-01-01

    The validation and verification of laboratory methods and procedures before their use in clinical testing is essential for providing a safe and useful service to clinicians and patients. This paper outlines the principles of validation and verification in the context of clinical human molecular gene

  3. 10. international mouse genome conference

    Energy Technology Data Exchange (ETDEWEB)

    Meisler, M.H.

    1996-12-31

    Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.

  4. 2004 Mutagenesis Gordon Conference

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Sue Jinks-Robertson

    2005-09-16

    Mutations are genetic alterations that drive biological evolution and cause many, if not all, human diseases. Mutation originates via two distinct mechanisms: ''vertical'' variation is de novo change of one or few bases, whereas ''horizontal'' variation occurs by genetic recombination, which creates new mosaics of pre-existing sequences. The Mutagenesis Conference has traditionally focused on the generation of mutagenic intermediates during normal DNA synthesis or in response to environmental insults, as well as the diverse repair mechanisms that prevent the fixation of such intermediates as permanent mutations. While the 2004 Conference will continue to focus on the molecular mechanisms of mutagenesis, there will be increased emphasis on the biological consequences of mutations, both in terms of evolutionary processes and in terms of human disease. The meeting will open with two historical accounts of mutation research that recapitulate the intellectual framework of this field and thereby place the current research paradigms into perspective. The two introductory keynote lectures will be followed by sessions on: (1) mutagenic systems, (2) hypermutable sequences, (3) mechanisms of mutation, (4) mutation avoidance systems, (5) mutation in human hereditary and infectious diseases, (6) mutation rates in evolution and genotype-phenotype relationships, (7) ecology, mutagenesis and the modeling of evolution and (8) genetic diversity of the human population and models for human mutagenesis. The Conference will end with a synthesis of the meeting as the keynote closing lecture.

  5. Genetic, epidemiological, and clinical aspects of hereditary pancreatitis: a population-based cohort study in Denmark

    DEFF Research Database (Denmark)

    Brusgaard, Klaus

    2010-01-01

    regulator gene (CFTR) and serine protease inhibitor Kazal type 1 gene (SPINK1) mutations with patients who retained the diagnosis of true idiopathic pancreatitis (tIP) after genetic testing for HP, SPINK1, and CFTR mutations. METHODS: Patients with PUO were identified in the Danish National Registry of...... Patients or were referred by clinicians. DNA from blood was analyzed for cationic trypsinogen (PRSS1), SPINK1, and CFTR mutations. Considering the diagnosis of HP, a pedigree was drawn for each patient. RESULTS: A genetic mutation was found in 40% of 122 patients with PUO. After testing first......-degree relatives of the 18 initially identified HP patients, 38 HP patients in total were identified, and 28 patients had SPINK1-CFTR mutations. Among HP patients, no p.N29I mutations were found and the p.A16V mutation was more frequent than previously reported, 45 and 32% had exocrine and endocrine insufficiency...

  6. The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Daniel J. Guerra

    2011-01-01

    Full Text Available Autism spectrum disorders (ASDs have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD.

  7. The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

    OpenAIRE

    Guerra, Daniel J.

    2011-01-01

    Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting th...

  8. The clinical and genetic features in a cohort of mainland Chinese patients with thyrotoxic periodic paralysis

    OpenAIRE

    Li, Xiaobing; YAO, SHENG; Xiang, Yining; Zhang, Xiaolei; Wu, Xiangbing; LUO, LAIMIN; Huang, Haihua; Zhu, Min; Wan, Hui; Hong, Daojun

    2015-01-01

    Background Thyrotoxic periodic paralysis (TPP) is a life-threatening channelopathy manifesting as recurrent episodes of hypokalemia and muscle weakness in the presence of hyperthyroidism. Recent findings indicate defects of inward rectifying K+ (Kir) channels are associated with some TPP patients. The associations are not only found in Caucasian population (mainly Brazilian), but also in Singaporean population. However, potential genetic risk factors for mainland Chinese patients, the largest...

  9. Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics

    OpenAIRE

    Kubota Takeo; Miyake Kunio; Hirasawa Takae

    2012-01-01

    Abstract Epigenetics is a mechanism that regulates gene expression independently of the underlying DNA sequence, relying instead on the chemical modification of DNA and histone proteins. Although environmental and genetic factors were thought to be independently associated with disorders, several recent lines of evidence suggest that epigenetics bridges these two factors. Epigenetic gene regulation is essential for normal development, thus defects in epigenetics cause various rare congenital ...

  10. Clinical and Genetic Correlates of Exercise Performance in Young Children with Cystic Fibrosis1,2

    OpenAIRE

    McBride, Michael G.; Schall, Joan I.; Zemel, Babette S.; Stallings, Virginia A.; Ittenbach, Richard F.; Paridon, Stephen M.

    2010-01-01

    Exercise performance in individuals with cystic fibrosis has been shown to be related to the degree of pulmonary dysfunction and undernutrition and genetic profile. The aim of this study was to examine these relationships in young children with cystic fibrosis. The participants were 64 children ages 8 to 11 years (M = 9.3, SD = 0.9) with cystic fibrosis and pancreatic insufficiency recruited from 13 different U.S. Cystic Fibrosis Centers. Assigned to one of three groups by Δ...

  11. The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease

    OpenAIRE

    Lam, Ping; Soroka, Carol J.; Boyer, James L.

    2010-01-01

    The primary transporter responsible for bile salt secretion is the bile salt export pump (BSEP, ABCB11), a member of the ATP-binding cassette (ABC) superfamily, which is located at the bile canalicular apical domain of hepatocytes. In humans, BSEP deficiency results in several different genetic forms of cholestasis, which include progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), as well as other acquired forms of cholestasi...

  12. Genetic diversity of Trichomonas vaginalis clinical isolates from Henan province in central China

    OpenAIRE

    Mao, Meng; Liu, Hui Li

    2015-01-01

    Trichomonas vaginalis is a flagellated protozoan parasite that infects the human urogenital tract, causing the most common non-viral, sexually transmitted disease worldwide. In this study, genetic variants of T. vaginalis were identified in Henan Province, China. Fragments of the small subunit of nuclear ribosomal RNA (18S rRNA) were amplified from 32 T. vaginalis isolates obtained from seven regions of Henan Province. Overall, 18 haplotypes were determined from the 18S rRNA sequences. Each s...

  13. Oral and Craniofacial Clinical Signs Associated to Genetic Conditions in Human Identification Part I: A Review

    OpenAIRE

    Ayoub, Fouad; Aoun, Nicole; el Husseini, Hassan; Jassar, Houssam; Sayah, Fida; Salameh, Ziad

    2015-01-01

    Background: Forensic dentistry is one of the most reliable methods used in human identification when other technique as fingerprint, DNA, visual identification cannot be used. Genetic disorders have several manifestations that can target the intra-oral cavity, the cranio-facial area or any location in the human body. Materials and Methods: A literature search of the scientific database (Medline and Science Direct) for the years 1990 to 2014 was carried out to find out all the available papers...

  14. Clinical characteristics and genetic analysis of three pediatric patients with idiopathic restrictive cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    杨世伟

    2013-01-01

    Objective Restrictive cardiomyopathy(RCM) is rare in children,and little is known about the molecular basis of RCM.The aim of this study was to investigate the clinical and myopathological characteristics and to detect

  15. Maternally Inherited Diabetes and Deafness (MIDD Syndrome: A Clinical and Molecular Genetic Study of a Taiwanese Family.

    Directory of Open Access Journals (Sweden)

    Yung-Nien Chen

    2004-01-01

    Full Text Available We report on a case of a 48-year-old woman presenting with maternally inherited diabetesmellitus and deafness (MIDD syndrome. Molecular genetic analysis and clinical evaluationwere conducted in the patient and her 4 children to investigate the interrelationbetween an MIDD-associated mitochondrial DNA (mtDNA mutation and clinical manifestations.Various symptoms and markers of MIDD, including seizures, migraines, shortstature, mental retardation, and stroke-like episodes, were reviewed. Diabetes mellitus (DMwas studied by oral glucose tolerance and glucagon stimulation tests. Hearing impairmentwas determined by standard hearing tests and a brainstem auditory evoked potential test.The A3243G and T3271C transitional mutations of mtDNA were investigated from muscleand/or leukocytes and hair follicles. Mitochondrial-related symptoms were not found in thechildren, although they all harbored a heteroplasmic A3243G transition of mtDNA, asdetected in screened samples. For the patient, the proportion of mutant mtDNA was highestin muscle cells followed by hair follicles and then leukocytes. Moreover, the proportion ofmutant mtDNA was also higher in hair follicles than in leukocytes for asymptomatic familymembers. This Taiwanese MIDD family was found to have the A3243G point mutation asrevealed from molecular genetic studies of leukocytes, hair follicles, and muscle tissue.However, no correlation was found between the proportion of mutant mtDNA and clinicalfeatures of any family member.

  16. Systematic review of 20 clinical pathological conference articles on tuberculosis%20篇结核病临床病理讨论系统回顾分析

    Institute of Scientific and Technical Information of China (English)

    何权瀛; 邹黎

    2005-01-01

    目的探讨结核病误诊的原因.方法手工检索近20年发表在中华结核和呼吸杂志等五种中华级杂志上的20篇有关结核病误诊的临床病理讨论(clinical pathological conference, CPC)文章,并逐一登记患者的临床特征、最后病理诊断、应吸取的教训等.结果 20例结核病中急性粟粒性结核13例,占65.0%;大量使用糖皮质激素引起结核活动、播散共8例,占40.0%.结论临床医生必须高度重视结核病的诊断,以期减少结核病漏诊.

  17. The genetic and metabolic determinants of cardiovascular complications in type 2 diabetes: recent insights from animal models and clinical investigations.

    Science.gov (United States)

    Kohen Avramoglu, Rita; Laplante, Marc-André; Le Quang, Khai; Deshaies, Yves; Després, Jean-Pierre; Larose, Eric; Mathieu, Patrick; Poirier, Paul; Pérusse, Louis; Vohl, Marie-Claude; Sweeney, Gary; Ylä-Herttuala, Seppo; Laakso, Markku; Uusitupa, Matti; Marette, André

    2013-10-01

    Cardiovascular complications (CVC) are the most common causes of death in patients with type 2 diabetes (T2D). However the pathophysiological determinants and molecular mechanisms involved in the progression of CVC in T2D are poorly understood. We have undertaken the challenging task of identifying some of the genetic and clinical determinants of CVC through a unique multidisciplinary approach involving Canadian and Finnish investigators. We are studying novel animal models combining atherosclerosis, diet-induced obesity and T2D to understand the molecular basis of CVC in obesity-linked T2D. We are also conducting clinical studies to identify key determinants of CVC in T2D patients and to determine whether a lifestyle modification program targeting loss of visceral adipose tissue/ectopic fat could be associated with clinical benefits in these patients. Together, we strongly believe that we can fill some gaps in our understanding of the CVC pathogenesis in T2D and identify novel therapeutic targets and hope that this new knowledge may be translated into the design of effective clinical interventions to optimally reduce cardiovascular risk in T2D subjects. PMID:24500564

  18. Genetic aberrations in small B-cell lymphomas and leukemias: molecular pathology, clinical relevance and therapeutic targets.

    Science.gov (United States)

    Bogusz, Agata M; Bagg, Adam

    2016-09-01

    Small B-cell lymphomas and leukemias (SBCLs) are a clinically, morphologically, immunophenotypically and genetically heterogeneous group of clonal lymphoid neoplasms, including entities such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL) and hairy cell leukemia (HCL). The pathogenesis of some of these lymphoid malignancies is characterized by distinct translocations, for example t(11;14) in the majority of cases of MCL and t(14;18) in most cases of FL, whereas other entities are associated with a variety of recurrent but nonspecific numeric chromosomal abnormalities, as exemplified by del(13q14), del(11q22), and +12 in CLL, and yet others such as LPL and HCL that lack recurrent or specific cytogenetic aberrations. The recent surge in next generation sequencing (NGS) technology has shed more light on the genetic landscape of SBCLs through characterization of numerous driver mutations including SF3B1 and NOTCH1 in CLL, ATM and CCND1 in MCL, KMT2D and EPHA7 in FL, MYD88 (L265P) in LPL, KLF2 and NOTCH2 in splenic MZL (SMZL) and BRAF (V600E) in HCL. The identification of distinct genetic lesions not only provides greater insight into the molecular pathogenesis of these disorders but also identifies potential valuable biomarkers for prognostic stratification, as well as specific targets for directed therapy. This review discusses the well-established and recently identified molecular lesions underlying the pathogenesis of SBCLs, highlights their clinical relevance and summarizes novel targeted therapies. PMID:27121112

  19. Genetic diversity of variants involved in drug response and metabolism in Sri Lankan populations: implications for clinical implementation of pharmacogenomics

    Science.gov (United States)

    Chan, Sze Ling; Samaranayake, Nilakshi; Ross, Colin J.D.; Toh, Meng Tiak; Carleton, Bruce; Hayden, Michael R.; Teo, Yik Ying; Dissanayake, Vajira H.W.

    2016-01-01

    Background Interpopulation differences in drug responses are well documented, and in some cases they correspond to differences in the frequency of associated genetic markers. Understanding the diversity of genetic markers associated with drug response across different global populations is essential to infer population rates of drug response or risk for adverse drug reactions, and to guide implementation of pharmacogenomic testing. Sri Lanka is a culturally and linguistically diverse nation, but little is known about the population genetics of the major Sri Lankan ethnic groups. The objective of this study was to investigate the diversity of pharmacogenomic variants in the major Sri Lankan ethnic groups. Methods We examined the allelic diversity of more than 7000 variants in genes involved in drug biotransformation and response in the three major ethnic populations of Sri Lanka (Sinhalese, Sri Lankan Tamils, and Moors), and compared them with other South Asian, South East Asian, and European populations using Wright’s Fixation Index, principal component analysis, and STRUCTURE analysis. Results We observed overall high levels of similarity within the Sri Lankan populations (median FST=0.0034), and between Sri Lankan and other South Asian populations (median FST=0.0064). Notably, we observed substantial differentiation between Sri Lankan and European populations for important pharmacogenomic variants related to warfarin (VKORC1 rs9923231) and clopidogrel (CYP2C19 rs4986893) response. Conclusion These data expand our understanding of the population structure of Sri Lanka, provide a resource for pharmacogenomic research, and have implications for the clinical use of genetic testing of pharmacogenomic variants in these populations. PMID:26444257

  20. Frequency of CFTR, SPINK1, and Cathepsin B Gene Mutation in North Indian Population: Connections between Genetics and Clinical Data

    Directory of Open Access Journals (Sweden)

    Shweta Singh

    2014-01-01

    Full Text Available Objectives. Genetic mutations and polymorphisms have been correlated with chronic pancreatitis (CP. This study aims to investigate the association of genetic variants of cystic fibrosis transmembrane conductance regulator (CFTR and serine protease inhibitor Kazal type 1 (SPINK-1 genes and Cathepsin B gene polymorphisms with CP and to associate genetic backgrounds with clinical phenotypes. Methods. 150 CP patients and 150 normal controls were enrolled consecutively. We analyzed SPINK-1 N34S and IVS3+2T>C gene mutations by PCR-restriction-fragment length polymorphism (RFLP. The identification of DF508, G551D, G542X, R117H, and W1282X mutations was carried out by ARMS-PCR. S549N mutation, IVS8 polyTn polymorphism, and Cathepsin B Lec26Val were analysed by PCR-RFLP, nested PCR, and PCR-RFLP plus sequencing, respectively. Results. We found a significant association of SPINK1 (N34S gene polymorphism. IVS1−37T>C polymorphism shows linkage with 101A>G. 300 chromosomes belonging to the CFTR subgroup exhibited minor allele frequency of 0.04, 0.03, 0.03, 0.013, 0.006, and 0.02 for DF508, G452X, G551D, S549N, R117H, and IVS8 T5, respectively. Except for R117H and IVS8 T5 polymorphisms, all other mutations showed significant variation. Conclusion. Analysis of potential susceptibility variants is needed to support nature of the genes and environment in pancreatitis. This data may help establish genetic screening and prenatal setup for Indian population.

  1. Clinical Research and Clinical Trials

    Science.gov (United States)

    ... Meetings, Conferences & Events Partnering & Donating to the NICHD Staff Directory ... Clinical Research Skip sharing on social media links Share this: Page Content Clinical research is research that directly involves a ...

  2. Conference summaries

    International Nuclear Information System (INIS)

    This volume contains conference summaries of the 28. annual conference of the Canadian Nuclear Association, and the 9. annual conference of the Canadian Nuclear Society. Topics of discussion include: power reactors; fuel cycles; nuclear power and public understanding; future trends; applications of nuclear technology; CANDU reactors; operational enhancements; design of small reactors; accident behaviour in fuel channels; fuel storage and waste management; reactor commissioning/decommissioning; nuclear safety experiments and modelling; the next generation reactors; advances in nuclear engineering education in Canada; safety of small reactors; current position and improvements of fuel channels; current issues in nuclear safety; and radiation applications - medical and industrial

  3. Comparative analysis of genetic background in eight near-isogenic wheat lines with different H genes conferring resistance to Hessian fly

    Science.gov (United States)

    Near-isogenic lines (NILs) are useful tools for investigating gene expression, detecting closely linked markers, or cloning the genes. However, the reliability of using NILs for genetic and genomic analysis relies on the homogeneity of the genetic background. In this study, a set of eight NILs (Car...

  4. PHYSICS FOR HEALTH: CONFERENCE

    CERN Multimedia

    2016-01-01

    ICTR-PHE 2016 - International Conference on Translational Research in Radio-Oncology and Physics for Health -, co organized by CERN, aims at developing new strategies to better diagnose and treat cancer, by uniting biology and physics with clinics. Through the various sessions and symposia, the scientific programme offers the delegates the opportunity to discuss, in a friendly atmosphere, the latest progress in physics breakthroughs for health applications. The third edition of this conference took place at CICG (Centre International de Conférence Genève) from 15 to 19 Feb 2016.

  5. Scaling ethics up and down: moral craft in clinical genetics and in global health research

    OpenAIRE

    Parker, Michael

    2015-01-01

    This paper engages with the question of what it is to ‘do good medical ethics’ in two ways. It begins with an exploration of what it might mean to say that health professionals practise good medical ethics as part of practising good ethical medicine. Using the example of the Genethics Club, a well-established national ethics forum for genetics professionals in the UK, the paper develops an account of moral craftsmanship grounded in the concepts of shared moral commitments and practices, moral...

  6. Clinical and genetic features of variegate porphyria in a Chinese patient

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Acute porphyria is rare in orientals. We describe a Chinese woman with recurrent generalised tonic-clonic seizures and abdominal pain. Genomic DNA studies identified a heterozygous base substitution from guanine to adenine at nucleotide position 503, resulting in substitution of arginine by histidine at position 168 of the protein (R168H). This genetic abnormality is similar to the mutation reported in Caucasians with variegate porphyria. To the best of our knowledge, this is the first report in the English literature a Chinese patient with variegate porphyria with an identifiable mutation. A brief review of porphyria is presented.

  7. Systematic review of the clinical and genetic aspects of Prader-Willi syndrome

    Directory of Open Access Journals (Sweden)

    Dong Kyu Jin

    2011-02-01

    Full Text Available Prader-Willi syndrome (PWS is a complex multisystem genetic disorder that is caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11&#8211;q13. This syndrome has a characteristic phenotype including severe neonatal hypotonia, early-onset hyperphagia, development of morbid obesity, short stature, hypogonadism, learning disabilities, behavioral problems, and psychiatric problems. PWS is an example of a genetic condition caused by genomic imprinting. It can occur via 3 main mechanisms that lead to the absence of expression of paternally inherited genes in the 15q11.2&#8211;q13 region: paternal microdeletion, maternal uniparental disomy, and an imprinting defect. Over 99% of PWS cases can be diagnosed using DNA methylation analysis. Early diagnosis of PWS is important for effective long-term management. Growth hormone (GH treatment improves the growth, physical phenotype, and body composition of patients with PWS. In recent years, GH treatment in infants has been shown to have beneficial effects on the growth and neurological development of patients diagnosed during infancy. There is a clear need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy in patients with PWS.

  8. Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Bourguignon, Michel H. [Direction Generale de la Surete Nucleaire et de la Radioprotection, Paris Cedex 12 (France); CEA-DSV-DRM Hopital, Service de Recherches en Hemato-Immunologie, Saint Louis, Paris (France); Gisone, Pablo A.; Perez, Maria R.; Michelin, Severino; Dubner, Diana; Giorgio, Marina di [Autoridad Regulatoria Nuclear, Laboratorio de Radiopatologia, Buenos Aires (Argentina); Carosella, Edgardo D. [CEA-DSV-DRM Hopital, Service de Recherches en Hemato-Immunologie, Saint Louis, Paris (France)

    2005-03-01

    Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are ''hypersensitive'' to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed. (orig.)

  9. Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection.

    Science.gov (United States)

    Bourguignon, Michel H; Gisone, Pablo A; Perez, Maria R; Michelin, Severino; Dubner, Diana; Giorgio, Marina Di; Carosella, Edgardo D

    2005-03-01

    Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are "hypersensitive" to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed. PMID:15692806

  10. Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications

    Directory of Open Access Journals (Sweden)

    Zetterberg Henrik

    2004-02-01

    Full Text Available Abstract The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. The firm association between increased homocysteine concentration and neural tube defects (NTD has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased fetal viability. There are several genetic polymorphisms that are associated with defects in folate- and vitamin B12-dependent homocysteine metabolism. The methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C polymorphisms cause elevated homocysteine concentration and are associated with an increased risk of NTD. Additionally, low concentration of vitamin B12 (cobalamin or transcobalamin that delivers vitamin B12 to the cells of the body leads to hyperhomocysteinemia and is associated with NTD. This effect involves the transcobalamin (TC 776C>G polymorphism. Importantly, the biochemical consequences of these polymorphisms can be modified by folate and vitamin B12 supplementation. In this review, I focus on recent studies on the role of hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human spontaneous abortion and discuss the possibility that periconceptional supplementation with folate and vitamin B12 might lower the incidence of miscarriage in women planning a pregnancy.

  11. Genetic heterogeneity within the HLA region in three distinct clinical subgroups of myasthenia gravis.

    Science.gov (United States)

    Saruhan-Direskeneli, Güher; Hughes, Travis; Yilmaz, Vuslat; Durmus, Hacer; Adler, Adam; Alahgholi-Hajibehzad, Mahdi; Aysal, Fikret; Yentür, Sibel P; Akalin, Mehmet Ali; Dogan, Oner; Marx, Alexander; Gülsen-Parman, Yesim; Oflazer, Piraye; Deymeer, Feza; Sawalha, Amr H

    2016-05-01

    This study aims to investigate genetic susceptibility to early-onset and late-onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome-wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR=5.71 [3.77-8.66], P=2.24×10(-16)), HLA-B*08:01 (OR=7.04 [3.95-12.52], P=3.34×10(-11)) and HLA-C*07:01 (OR=2.74 [1.97-3.81], P=2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR=2.22 [1.59-3.09], P=2.48×10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR=5.86, P=2.25×10(-14)) and HLA-DQB1*05:02 (OR=8.56, P=6.88×10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey. PMID:27181991

  12. Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection

    International Nuclear Information System (INIS)

    Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are ''hypersensitive'' to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed. (orig.)

  13. Clinical, histopathological and genetic studies in a family with fatal familial insomnia.

    Science.gov (United States)

    Shi, Xiao-Hong; Han, Jun; Zhang, Jin; Shi, Qi; Chen, Jian-Ming; Xia, Sheng-Li; Xie, Zhi-Qiang; Shen, Xiao-Jing; Shan, Bing; Lei, Yan-Jun; Shi, Song; Zhou, Wei; Zhang, Bao-Yun; Gao, Chen; Liu, Ying-Hui; Song, Juan; Guo, Yan-Jun; Wang, De-Xin; Xu, Bian-Li; Dong, Xiao-Ping

    2010-03-01

    We compared clinical data from two related Chinese patients with fatal familial insomnia (FFI) and collected information about their pedigree. The clinical features in the two cases were similar and included initial progressive insomnia and sympathetic activation, which persisted throughout the clinical course. A total of 135 members of this family, across seven generations, were retrospectively investigated. Eleven family members, including the two FFI cases, were found to have died with similar neurological problems. Analysis of PRNP in 32 family members revealed eleven carrying the D178N allele, including the two FFI patients. Spongiform degeneration in brains was not found, but gliosis was obvious in the thalamus of the two cases at postmortem. Proteinase K-resistant prion protein (PrP) was not found in proband's brain by immunohistochemistry, but observed in some areas of brain for both cases by PrP-specific Western blot. Investigation of the pedigree has led to the identification of an additional 9 family members who had similar clinical symptoms and 9 currently healthy individuals with the D178N mutation. PMID:20096809

  14. Genetic Environment and Transcription of ampC in an Acinetobacter baumannii Clinical Isolate

    OpenAIRE

    Segal, Heidi; Nelson, E C; Elisha, B. Gay

    2004-01-01

    An ampC gene was cloned from a clinical isolate of Acinetobacter baumannii (strain RAN). DNA sequencing and primer extension studies showed that ampC is transcribed from a promoter contained within a putative insertion sequence element which has been found to abut several different genes in Acinetobacter spp.

  15. Clinical, histopathological and genetic studies in a case of fatal familial insomnia with review of the literature.

    Science.gov (United States)

    Peng, Bin; Zhang, Shenqi; Dong, Hongjuan; Lu, Zuneng

    2015-01-01

    To explore clinical, histopathological and genetic features of a case with fatal familial insomnia (FFI) and review the related literatures. A middle-aged woman who complained of "insomnia for 9 months and psychosis for 3 months" was suspicious of FFI. The clinical features of the patient were analyzed, and the dead patient was examined by autopsy and the brain tissues were obtained for histopathological studies, and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP). The main clinical features included intractable insomnia, psychiatric symptoms and abnormal night sleep behavior, unsteady gait, difficulty swallowing, sudden death, and positive family history. The pathological studies showed neuronal loss and gliosis of multiple brain tissues in the proband, predominated with thalamus; and analysis of PRNP revealed gene D178N mutation, and linkage with 129 methionine (Met) allele in the proband and a relative. FFI patients may manifest as sudden death, and may have prominent psychiatric symptoms; the corresponding gene mutation could occur in the asymptomatic carriers; the data of autopsy and brain tissue pathology is helpful for further understanding of this disease. PMID:26617725

  16. Genetic variability analysis among clinical Candida spp. isolates using random amplified polymorphic DNA

    Directory of Open Access Journals (Sweden)

    Patrícia M Pinto

    2004-03-01

    Full Text Available The patterns of genetic variation of samples of Candida spp. isolated from patients infected with human immunodeficiency virus in Vitória, state of Espírito Santo, Brazil, were examined. Thirty-seven strains were isolated from different anatomical sites obtained from different infection episodes of 11 patients infected with the human immunodeficiency virus (HIV. These samples were subjected to randomly amplified polymorphic DNA (RAPD analysis using 9 different primers. Reproducible and complex DNA banding patterns were obtained. The experiments indicated evidence of dynamic process of yeast colonization in HIV-infected patients, and also that certain primers are efficient in the identification of species of the Candida genus. Thus, we conclude that RAPD analysis may be useful in providing genotypic characters for Candida species typing in epidemiological investigations, and also for the rapid identification of pathogenic fungi.

  17. Genetic diversity of the VP1/VP2 gene of canine parvovirus type 2b amplified from clinical specimens in Brazil

    OpenAIRE

    Pereira Cesar A. D.; Durigon Edison Luiz

    2000-01-01

    We evaluated the genetic diversity in the VP1/VP2 gene of CPV type 2b isolates from symptomatic dogs in Brazil. A total of 21 isolates collected from 1990 through 1995 previously typed as CPV2b by PCR assay were studied. Overall we found a high degree of similarity among sequences from different CPV clinical isolates collected. Genetic analysis of this selected region gave no indication of a specific Brazilian parvovirus lineage.

  18. Genetic diversity of the VP1/VP2 gene of canine parvovirus type 2b amplified from clinical specimens in Brazil

    Directory of Open Access Journals (Sweden)

    Pereira Cesar A. D.

    2000-01-01

    Full Text Available We evaluated the genetic diversity in the VP1/VP2 gene of CPV type 2b isolates from symptomatic dogs in Brazil. A total of 21 isolates collected from 1990 through 1995 previously typed as CPV2b by PCR assay were studied. Overall we found a high degree of similarity among sequences from different CPV clinical isolates collected. Genetic analysis of this selected region gave no indication of a specific Brazilian parvovirus lineage.

  19. Genetic analysis of clinical isolates of Leishmania major from Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Gilda Eslami, Rasoul Salehi, Sharifeh Khosravi & Monir Doudi

    2012-09-01

    Full Text Available Background & objectives: Leishmaniasis is a geographically widespread severe disease which includes visceralleishmaniasis (VL and cutaneous leishmaniasis (CL. There are 350 million people at risk in over 80 countries.In the Old World, CL is usually caused by Leishmania major, L. tropica, and L. aetiopica complex of which 90%of cases occur in Afghanistan, Algeria, Iran, Iraq, Saudi Arabia, Syria, Brazil and Peru. Recently, Eslami et al(2011 reported a novel TRYP6 gene encoding tryparedoxin peroxidase from an Iranian L. major strain exhibitinghomology with the related gene in a divergent genus of Kinetoplastida, the Crithidia. This prompted us toanalyze the mentioned gene in 100 isolates obtained from patients with suspected CL. Consequently, we analyzedinternal transcribed spacer 1 (ITS1 region, RNA polymerase II largest subunit (RPOIILS and the mitochondrialDNA polymerase beta (DPOLB.Methods: After obtaining samples from 100 patients, DNA extraction was performed and TRYP6 was analyzedusing conventional PCR. All samples harbouring TRYP6 with smaller size (555 bp were analysed based onthree other regions: ITS1, RPOIILS and DPOLB genes.Results: Results showed that 10% of the isolates have the same character as observed in our previous study. TheITS1-RFLP-PCR of this 10% isolates showed their similarity to the one from Crithidia fasciculata. RNApolymerase II largest subunit (RPOIILS showed genetic diversity but the mitochondrial DNA polymerase beta(DPOLB did not show any genetic diversity.Conclusion: This study might also help in solving the problems concerning Leishmaniasis outbreaks currentlyreported in Iran and some other endemic regions of the world.

  20. Correlation between genetic variability and virulence factors in clinical strains of Malassezia pachydermatis of animal origin.

    Science.gov (United States)

    Buommino, Elisabetta; Nocera, Francesca Paola; Parisi, Annamaria; Rizzo, Antonietta; Donnarumma, Giovanna; Mallardo, Karina; Fiorito, Filomena; Baroni, Adone; De Martino, Luisa

    2016-09-01

    Malassezia pachydermatis is a yeast belonging to the microbiota of the skin and mucous membranes of dog and cat, but it can also act as pathogen, causing dermatitis. The aim of this work was to evaluate the genetic variability of M. pachydermatis strains isolated from symptomatic dogs and cats and determine a correlation between genotype and phenotype. For this purpose eleven strains of M. pachydermatis were molecularly classified by nested-polymerase chain reaction (nested-PCR) based on ITS-1 and ITS-2 regions, specific for fungal rRNA genes. Furthermore, random amplification of polymorphic DNA (RAPD) was applied for genetic typing of M. pachydermatis isolates identifying four different genotypes. Strains belonging to genotype 1 produced the highest amount of biofilm and phospholipase activity. The inflammatory response induced by M. pachydermatis strains in immortalized human keratinocytes (HaCat cells) was significantly different when we compared the results obtained from each strain. In particular, HaCat cells infected with the strains belonging to genotypes 1 and 2 triggered the highest levels of increase in TLR-2, IL-1β, IL-6, IL-8, COX-2 and MMP-9 expression. By contrast, cells infected with the strains of genotype 3 and those of genotype 4 did not significantly induce TLR-2 and cytokines. The results obtained might suggest a possible association between genotype and virulence factors expressed by M. pachydermatis strains. This highlights the need for a more accurate identification of the yeast to improve the therapeutic approach and to monitor the onset of human infections caused by this emergent zoonotic pathogen. PMID:27602421

  1. Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hageman Gregory S

    2011-07-01

    Full Text Available Abstract Predictive tests for estimating the risk of developing late-stage neovascular age-related macular degeneration (AMD are subject to unique challenges. AMD prevalence increases with age, clinical phenotypes are heterogeneous and control collections are prone to high false-negative rates, as many control subjects are likely to develop disease with advancing age. Risk prediction tests have been presented previously, using up to ten genetic markers and a range of self-reported non-genetic variables such as body mass index (BMI and smoking history. In order to maximise the accuracy of prediction for mainstream genetic testing, we sought to derive a test comparable in performance to earlier testing models but based purely on genetic markers, which are static through life and not subject to misreporting. We report a multicentre assessment of a larger panel of single nucleotide polymorphisms (SNPs than previously analysed, to improve further the classification performance of a predictive test to estimate the risk of developing choroidal neovascular (CNV disease. We developed a predictive model based solely on genetic markers and avoided inclusion of self-reported variables (eg smoking history or non-static factors (BMI, education status that might otherwise introduce inaccuracies in calculating individual risk estimates. We describe the performance of a test panel comprising 13 SNPs genotyped across a consolidated collection of four patient cohorts obtained from academic centres deemed appropriate for pooling. We report on predictive effect sizes and their classification performance. By incorporating multiple cohorts of homogeneous ethnic origin, we obtained >80 per cent power to detect differences in genetic variants observed between cases and controls. We focused our study on CNV, a subtype of advanced AMD associated with a severe and potentially treatable form of the disease. Lastly, we followed a two-stage strategy involving both test model

  2. Genetic testing for young-onset colorectal cancer: case report and evidence-based clinical guidelines

    OpenAIRE

    Zhou, Yaolin; Boardman, Lisa A; Miller, Robert C.

    2010-01-01

    Background Young-onset colorectal cancer is clinicopathologically different from older-onset colorectal cancer and tends to occur in patients with hereditary germline conditions such as Lynch syndrome and familial adenomatous polyposis. Case report. We describe the case of a 44-year-old man with a paternal history of colon polyps, a personal 2-year history of hematochezia, and a diagnosis of rectal cancer. Further clinical evaluation of the patient at our institution determined the cancer to ...

  3. Practical aspects of genetic identification of hallucinogenic and other poisonous mushrooms for clinical and forensic purposes

    OpenAIRE

    Kowalczyk, Marek; Sekuła, Andrzej; Mleczko, Piotr; Olszowy, Zofia; Kujawa, Anna; Zubek, Szymon; Kupiec, Tomasz

    2015-01-01

    Aim To assess the usefulness of a DNA-based method for identifying mushroom species for application in forensic laboratory practice. Methods Two hundred twenty-one samples of clinical forensic material (dried mushrooms, food remains, stomach contents, feces, etc) were analyzed. ITS2 region of nuclear ribosomal DNA (nrDNA) was sequenced and the sequences were compared with reference sequences collected from the National Center for Biotechnology Information gene bank (GenBank). Sporological ide...

  4. Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family

    OpenAIRE

    Tabernero, C; Polo, J.; Sevillano, M.; Munoz, R.; Berciano, J; Cabello, A.; Baez, B; Ricoy, J; Carpizo, R; Figols, J.; Cuadrado, N; Claveria, L

    2000-01-01

    The clinical presentation and evolution, neuropathological findings, and genotyping of three members of a Spanish family affected with fatal familial insomnia are reported. The mother and two of her offspring developed a rapidly evolving disease with insomnia and behavioural disorders as the initial symptoms and died between 5 and 10 months after the onset of the illness. Frontal brain biopsy in the mother disclosed only non-significant spongiosis, and full neuropathological ex...

  5. Genetic diversity of clinical isolates of Bacillus cereus using multilocus sequence typing

    Directory of Open Access Journals (Sweden)

    Pruckler James M

    2008-11-01

    Full Text Available Abstract Background Bacillus cereus is most commonly associated with foodborne illness (diarrheal and emetic but is also an opportunistic pathogen that can cause severe and fatal infections. Several multilocus sequence typing (MLST schemes have recently been developed to genotype B. cereus and analysis has suggested a clonal or weakly clonal population structure for B. cereus and its close relatives B. anthracis and B. thuringiensis. In this study we used MLST to determine if B. cereus isolates associated with illnesses of varying severity (e.g., severe, systemic vs. gastrointestinal (GI illness were clonal or formed clonal complexes. Results A retrospective analysis of 55 clinical B. cereus isolates submitted to the Centers for Disease Control and Prevention between 1954 and 2004 was conducted. Clinical isolates from severe infections (n = 27, gastrointestinal (GI illness (n = 18, and associated isolates from food (n = 10 were selected for analysis using MLST. The 55 isolates were diverse and comprised 38 sequence types (ST in two distinct clades. Of the 27 isolates associated with serious illness, 13 clustered in clade 1 while 14 were in clade 2. Isolates associated with GI illness were also found throughout clades 1 and 2, while no isolates in this study belonged to clade 3. All the isolates from this study belonging to the clade 1/cereus III lineage were associated with severe disease while isolates belonging to clade1/cereus II contained isolates primarily associated with severe disease and emetic illness. Only three STs were observed more than once for epidemiologically distinct isolates. Conclusion STs of clinical B. cereus isolates were phylogenetically diverse and distributed among two of three previously described clades. Greater numbers of strains will need to be analyzed to confirm if specific lineages or clonal complexes are more likely to contain clinical isolates or be associated with specific illness, similar to B. anthracis and

  6. SPINAL MUSCULAR ATROPHY FROM NORTHERN IRAN: A CLINICAL AND GENETIC SPECTRUM OF TEN PATIENTS

    Directory of Open Access Journals (Sweden)

    M.R. Salehi Omran

    2008-10-01

    Full Text Available AbstractObjectiveAutosomal recessive spinal muscular atrophy (SMA is, after cystic fibrosis, the second most common fatal monogenic disorder and the second most common hereditary neuromuscular disease after duchenne dystrophy. The disease is characterized by degeneration of anterior horn cells leading to progressiveparalysis with muscular atrophy. Depending on the clinical type (Werdnig- Hoffmann = type I, intermediate form = type II, Kugelberg-Welander = type III, some workers also have delineated an adult form of SMA (SMA type 4.SMA causes early death or increasing disability in childhood. The aim of this investigation was to describe the clinical findings of patients with spinal muscular atrophy (SMA with survival motor neuron (SMN gene deletion.Materials & methodsThis is a descriptive study conducted on 10 patients of SMA, confirmed by deletion of the SMN gene. All 10 patients had symmetrical muscle weakness, which was diffuse in those with onset of symptoms up to 1 months of age, and either proximal or predominant in lower limbs. Frequency determination of positive clinical and laboratory data was done according to revised diagnostic criteriaResultsIt was found that all patients with SMA had homozygous deletions of exons 7 and 8 of the survival motor neuron 1 (SMN1 gene, which is one of the candidate genes identified within 5q13. Fasciculations, atrophy and decreased DTR were frequent findings. Laboratory metabolic tests and all brain CT scans were normal. EMG and NCV findings, all showed normal motor and Sensory NCV and denervation of muscles of upper and lower extremities were compatible with a diagnosis of spinal muscular atrophy.ConclusionOur results confirm that SMN1 copy number analysis is an important parameter for identification of couples at risk of having a child affected with SMA and reduces unwarranted prenatal diagnosis for SMA.Keywords: Spinal muscular atrophy, SMN Gene, clinical findings, EMG, NCV 

  7. Different clinical outcomes of Entamoeba histolytica in Malaysia: does genetic diversity exist?

    OpenAIRE

    Anuar, Tengku Shahrul; Al-Mekhlafi, Hesham M.; Abdul Ghani, Mohamed Kamel; Azreen, Siti Nor; Salleh, Fatmah Md; Ghazali, Nuraffini; Bernadus, Mekadina; Moktar, Norhayati

    2013-01-01

    International audience The present study was conducted to investigate the clinical outcomes of Entamoeba histolytica infection in symptomatic and asymptomatic Orang Asli (aborigine) communities in Malaysia. Examination was performed on 500 stool samples obtained from Orang Asli communities in 3 different states using formalin-ether concentration, trichrome staining, and single-round PCR techniques. Out of 500 stool samples, single infection of E. histolytica, Entamoeba dispar, and Entamoeb...

  8. Genetic variants in matrix metalloproteinase genes as disposition factors for ovarian cancer risk, survival, and clinical outcome.

    Science.gov (United States)

    Wang, Yan; Ye, Yuanqing; Lin, Jie; Meyer, Larissa; Wu, Xifeng; Lu, Karen; Liang, Dong

    2015-06-01

    Ovarian cancer is one of the leading female cancers in the United States. Challenges remain in early diagnosis of this deadly disease. Matrix metalloproteinases (MMPs) family genes are paradoxically involved in cancer promotion and suppression. We hypothesize that genetic variants in MMP genes are associated with ovarian cancer development, so they could be potential markers for ovarian cancer diagnosis and prognosis. In this study of 417 ovarian cancer cases and 417 healthy controls, we genotyped a comprehensive panel of 266 single nucleotide polymorphisms (SNPs) in 23 MMP genes and analysed their associations with ovarian cancer risk, overall survival and treatment response in ovarian cancer cases who received platinum-based chemotherapy with surgery. In the analysis on 339 Caucasian cases and 349 Caucasian controls, 4 SNPs were significantly associated with cancer risk. The most significant association was observed for rs2292730 (OR = 2.03, 95% CI = 1.39-2.96, P = 0.0002). Classification and regression tree analysis identified four terminal nodes with differential risk of ovarian cancer. Thirty-four SNPs were significantly associated with overall survival and four of which showed significant association with response to chemotherapy. Unfavourable genotype analysis of top SNPs on overall risk of death showed significant gene-dosage effect, survival tree analysis differentiated patients into distinct risk groups based on their genetic profiles with median survival times (MSTs) ranging from 17.7 to 151.7 months. In conclusion, our results suggest that genetic variants in MMP pathway genes may modulate the risk and clinical outcomes of ovarian cancer, both individually and jointly. PMID:25867973

  9. A Novel Clinical Decision Support System Using Improved Adaptive Genetic Algorithm for the Assessment of Fetal Well-Being

    Directory of Open Access Journals (Sweden)

    Sindhu Ravindran

    2015-01-01

    Full Text Available A novel clinical decision support system is proposed in this paper for evaluating the fetal well-being from the cardiotocogram (CTG dataset through an Improved Adaptive Genetic Algorithm (IAGA and Extreme Learning Machine (ELM. IAGA employs a new scaling technique (called sigma scaling to avoid premature convergence and applies adaptive crossover and mutation techniques with masking concepts to enhance population diversity. Also, this search algorithm utilizes three different fitness functions (two single objective fitness functions and multi-objective fitness function to assess its performance. The classification results unfold that promising classification accuracy of 94% is obtained with an optimal feature subset using IAGA. Also, the classification results are compared with those of other Feature Reduction techniques to substantiate its exhaustive search towards the global optimum. Besides, five other benchmark datasets are used to gauge the strength of the proposed IAGA algorithm.

  10. Advanced Genetic Testing Comes to the Pain Clinic to Make a Diagnosis of Paroxysmal Extreme Pain Disorder

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    Ashley Cannon

    2016-01-01

    Full Text Available Objective. To describe the use of an advanced genetic testing technique, whole exome sequencing, to diagnose a patient and their family with a SCN9A channelopathy. Setting. Academic tertiary care center. Design. Case report. Case Report. A 61-year-old female with a history of acute facial pain, chronic pain, fibromyalgia, and constipation was found to have a gain of function SCN9A mutation by whole exome sequencing. This mutation resulted in an SCN9A channelopathy that is most consistent with a diagnosis of paroxysmal extreme pain disorder. In addition to the patient being diagnosed, four siblings have a clinical diagnosis of SCN9A channelopathy as they have consistent symptoms and a sister with a known mutation. For treatment, gabapentin was ineffective and carbamazepine was not tolerated. Nontraditional therapies improved symptoms and constipation resolved with pelvic floor retraining with biofeedback. Conclusion. Patients with a personal and family history of chronic pain may benefit from a referral to Medical Genetics. Pelvic floor retraining with biofeedback should be considered for patients with a SCN9A channelopathy and constipation.

  11. Update on Genetic Susceptibility and Pathogenesis in Juvenile Idiopathic Arthritis

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    Morten Herlin

    2014-07-01

    Full Text Available Juvenile idiopathic arthritis (JIA is a multifactorial disease with a pathogenesis which remains inexplicable. However, genome-wide association studies brought forward within recent years have discovered several new susceptibility genes, and accumulating evidence supports genetic variability as playing a key role in JIA development. This review summarises the present knowledge of human leukocyte antigen (HLA and non-HLA polymorphisms conferring disease susceptibility, and discusses the areas in JIA genetics, which are still to be investigated in order to apply JIA genetics in a clinical setting.

  12. Points to consider for prioritizing clinical genetic testing services: a European consensus process oriented at accountability for reasonableness.

    Science.gov (United States)

    Severin, Franziska; Borry, Pascal; Cornel, Martina C; Daniels, Norman; Fellmann, Florence; Victoria Hodgson, Shirley; Howard, Heidi C; John, Jürgen; Kääriäinen, Helena; Kayserili, Hülya; Kent, Alastair; Koerber, Florian; Kristoffersson, Ulf; Kroese, Mark; Lewis, Celine; Marckmann, Georg; Meyer, Peter; Pfeufer, Arne; Schmidtke, Jörg; Skirton, Heather; Tranebjærg, Lisbeth; Rogowski, Wolf H

    2015-06-01

    Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to develop shared prioritization criteria. Resources are currently too limited to fund all the beneficial genetic testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit of information for important life decisions, benefit for other people apart from the person tested and the patient-specific likelihood of being affected by the condition tested for. It may be subject to a finite time window. Health need includes the severity of the condition tested for and its progression at the time of testing. Further discussion and better evidence is needed before clearly defined recommendations can be made or a prioritization algorithm proposed. To our knowledge, this is the first time a clinical society has initiated a decision process about health-care prioritization on a European level, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management. PMID:25248395

  13. The dawn of Aurora kinase research: from fly genetics to the clinic.

    Directory of Open Access Journals (Sweden)

    Mar eCarmena

    2015-11-01

    Full Text Available Aurora kinases comprise a family of highly conserved serine-threonine protein kinases that play a pivotal role in the regulation of cell cycle. Aurora kinases are not only involved in the control of multiple processes during cell division but also coordinate chromosomal and cytoskeletal events, contributing to the regulation of checkpoints and ensuring the smooth progression of the cell cycle.Because of their fundamental contribution to cell cycle regulation, Aurora kinases were originally identified in independent genetic screens designed to find genes involved in the regulation of cell division. The first aurora mutant was part of a collection of mutants isolated in C. Nusslein-Volhard’s laboratory. This collection was screened in D. M. Glover’s laboratory in search for mutations disrupting the centrosome cycle in embryos derived from homozygous mutant mothers. The mutants identified were given names related to the polar regions, and included not only aurora but also the equally famous polo. Ipl1, the only Aurora in yeast, was identified in a genetic screen looking for mutations that caused chromosome segregation defects. The discovery of a second Aurora-like kinase in mammals opened a new chapter in the research of Aurora kinases. The rat kinase AIM was found to be highly homologous to the fly and yeast proteins, but localised at the midzone and midbody and was proposed to have a role in cytokinesis. Homologs of the equatorial Aurora (Aurora B were identified in metazoans ranging from flies to humans. Xenopus Aurora B was found to be in a complex with the chromosomal passenger INCENP, and both proteins were shown to be essential in flies for chromosome structure, segregation, central spindle formation and cytokinesis. Fifteen years on, Aurora kinase research is an active field of research. After the successful introduction of the first anti-mitotic agents in cancer therapy, both Auroras have become the focus of attention as targets for

  14. SPINAL MUSCULAR ATROPHY FROM NORTHERN IRAN: A CLINICAL AND GENETIC SPECTRUM OF TEN PATIENTS

    Directory of Open Access Journals (Sweden)

    M.R. Salehi Omran

    2008-06-01

    Full Text Available ObjectiveAutosomal recessive spinal muscular atrophy (SMA is, after cystic fibrosis, the second most common fatal monogenic disorder and the second most common hereditary neuromuscular disease after duchenne dystrophy. The disease is characterized by degeneration of anterior horn cells leading to progressiveparalysis with muscular atrophy. Depending on the clinical type (Werdnig- Hoffmann = type I, intermediate form = type II, Kugelberg-Welander = type III, some workers also have delineated an adult form of SMA (SMA type 4.SMA causes early death or increasing disability in childhood. The aim of this investigation was to describe the clinical findings of patients with spinal muscular atrophy (SMA with survival motor neuron (SMN gene deletion.Materials & methodsThis is a descriptive study conducted on 10 patients of SMA, confirmed by deletion of the SMN gene. All 10 patients had symmetrical muscle weakness, which was diffuse in those with onset of symptoms up to 1 months of age, and either proximal or predominant in lower limbs. Frequency determination of positive clinical and laboratory data was done according to revised diagnostic criteriaResultsIt was found that all patients with SMA had homozygous deletions of exons 7 and 8 of the survival motor neuron 1 (SMN1 gene, which is one of the candidate genes identified within 5q13. Fasciculations, atrophy and decreased DTR were frequent findings. Laboratory metabolic tests and all brain CT scans were normal. EMG and NCV findings, all showed normal motor and Sensory NCV and denervation of muscles of upper and lower extremities were compatible with a diagnosis of spinal muscular atrophy.ConclusionOur results confirm that SMN1 copy number analysis is an important parameter for identification of couples at risk of having a child affected with SMA and reduces unwarranted prenatal diagnosis for SMA.

  15. Clinical, haematological, and genetic studies of type 2 normal Hb A2 beta thalassaemia.

    OpenAIRE

    Metaxotou-Mavromati, A; Kattamis, C; Matathia, L; Tzetis, M; Kanavakis, E

    1988-01-01

    The clinical and haematological phenotype as well as chain synthesis data were studied in 35 doubly heterozygous patients with either normal Hb A2 and Hb F, type 2 beta thalassaemia and beta (high A2) thalassaemia (26 patients), or type 2 and other rare beta or delta beta variants (nine patients). Patients doubly heterozygous for type 2 and beta zero or delta beta zero thalassaemia variants had no detectable Hb A, indicating that the type 2 normal A2 beta thalassaemia is primarily the result ...

  16. Glucose transporter-1 deficiency syndrome: The expanding clinical and genetic spectrum of a treatable disorder

    OpenAIRE

    Leen, Wilhelmina; Klepper, Joerg; Verbeek, Marcel; Leferink, Maike; Hofste, Tom; van Engelen, Baziel; Wevers, Ron; Arthur, Todd; Bahi-Buisson, Nadia; Ballhausen, Diana; Bekhof, Jolita; Van Bogaert, Patrick; Carrilho, Inês; Chabrol, Brigitte; Champion, Michael

    2010-01-01

    textabstractGlucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41) and subsequently in three clinically affected family members. In these 57 patients...

  17. GM1 gangliosidosis and Morquio B disease: An update on genetic alterations and clinical findings

    OpenAIRE

    2011-01-01

    Abstract GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000- 1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected and compared with those in literature. In silico ...

  18. Stüve-Wiedemann Syndrome: Update on Clinical and Genetic Aspects.

    Science.gov (United States)

    Romeo Bertola, Débora; Honjo, Rachel S; Baratela, Wagner A R

    2016-04-01

    Stüve-Wiedemann syndrome is a rare autosomal recessive disorder characterized by bowed long bones, joint restrictions, dysautonomia, and respiratory and feeding difficulties, leading to death in the neonatal period and infancy in several occasions. Since the first cases in 1971, much has been learned about this condition, including its molecular basis - mutations in the leukemia inhibitory factor receptor gene (LIFR) -, natural history and management possibilities. This review aims to highlight the clinical aspects, radiological features, molecular findings, and management strategies in Stüve-Wiedemann syndrome. PMID:27194968

  19. Mendel conference

    CERN Document Server

    2015-01-01

    This book is a collection of selected accepted papers of Mendel conference that has been held in Brno, Czech Republic in June 2015. The book contents three chapters which represent recent advances in soft computing including intelligent image processing and bio-inspired robotics.: Chapter 1: Evolutionary Computing, and Swarm intelligence, Chapter 2: Neural Networks, Self-organization, and Machine Learning, and Chapter3: Intelligent Image Processing, and Bio-inspired Robotics. The Mendel conference was established in 1995, and it carries the name of the scientist and Augustinian priest Gregor J. Mendel who discovered the famous Laws of Heredity. In 2015 we are commemorating 150 years since Mendel's lectures, which he presented in Brno on February and March 1865. The main aim of the conference was to create a periodical possibility for students, academics and researchers to exchange their ideas and novel research methods.  .

  20. Preimplantation genetic diagnosis for inherited breast cancer: first clinical application and live birth in Spain.

    Science.gov (United States)

    Ramón Y Cajal, Teresa; Polo, Ana; Martínez, Olga; Giménez, Carles; Arjona, César; Llort, Gemma; Bassas, Lluís; Viscasillas, Pere; Calaf, Joaquin

    2012-06-01

    Carriers of a mutation in BRCA1/2 genes confront a high lifetime risk of breast and ovarian cancer and fifty percent probability of passing the mutation to their offspring. Current options for risk management influence childbearing decisions. The indications for preimplantation genetic diagnosis (PGD) have now been expanded to include predisposition for single-gene, late-onset cancer but few cases have been reported to date despite the favorable opinion among professionals and carriers. A 28-year-old BRCA1 mutation carrier (5273G>A in exon 19) with a strong maternal history of breast cancer and 2 years of infertility decided to pursue PGD to have a healthy descendent after an accurate assessment of her reproductive options. The procedure was approved by the national regulation authority and a PGD cycle was initiated. Four out of 6 embryos harbored the mutation. The two unaffected embryos were implanted in the uterus. A singleton pregnancy was achieved and a male baby was delivered at term. Consented umbilical cord blood testing confirmed the accuracy of the technique. Individualized PGD for inherited breast predisposition is feasible in the context of a multidisciplinary team. PMID:22179695

  1. The genetics of Leigh syndrome and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Ruhoy IS

    2014-11-01

    Full Text Available Ilene S Ruhoy, Russell P Saneto Division of Pediatric Neurology, Seattle Children's Hospital/University of Washington, Seattle, WA, USAAbstract: Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient's family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms.Keywords: mitochondrial disorder, neurodegeneration, multisystemic disease, oxidative phosphorylation, mitochondrial DNA, neuroimaging, seizures

  2. Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells.

    Science.gov (United States)

    Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A; Fink, Kyle D

    2016-05-01

    Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system. PMID:27335539

  3. Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells

    Science.gov (United States)

    Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A.; Fink, Kyle D.

    2016-01-01

    Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system. PMID:27335539

  4. A new recombinant factor VIII: from genetics to clinical use

    Directory of Open Access Journals (Sweden)

    Santagostino E

    2014-12-01

    Full Text Available Elena Santagostino Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy Abstract: Advances in recombinant technology and knowledge about coagulation factor VIII (FVIII are building a platform for new therapeutic options in patients with hemophilia A. The development of turoctocog alfa, a novel, high-purity, third-generation, B-domain truncated recombinant FVIII, has been produced and formulated without the use of animal-derived or human serum-derived components, in the wake of understanding of the new biochemical characteristics of FVIII, namely its protein structure, and glycosylation and sulfating patterns. Culture conditions and a five-step purification process have been developed to optimize the safety of turoctocog alfa. The results of two pilot clinical trials using turoctocog alfa confirmed high safety levels, with no patient developing inhibitors during the period of observation. The purpose of this review is to describe briefly the molecular and biological properties of turoctocog alfa, together with details of its clinical development, with emphasis on the needs of patients with hemophilia A. Keywords: hemophilia A, recombinant factor VIII, turoctocog alfa, purification, inhibitor, safety

  5. Conference Notification

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Roskill Information Services and Metal Events Ltd areorganizing the 2nd International Rare Earths Conference,which will be held at the Conrad Hotel in Hong Kong onFebruary 28 to March 2 2006.The program is structured tocover all the main aspects of the rare earths industry,including development of Chinese rare earth industry; trendsin rare earths demand; potential constraints on supply;research on potential capacity of rare earths supply chain.Global rare earths consumers will attend the conference.Registra...

  6. Leipzig Conference

    International Nuclear Information System (INIS)

    Showcase for a memorable year of progress in particle physics, the 22nd International Conference on High Energy Physics was held in Leipzig, German Democratic Republic, from 19-25 July. After a busy three days of parallel sessions (four streams), well over a thousand participants gathered in Leipzig's Kongresshalle for the plenary talks. As at the Brighton Conference last year, these began with presentations from the big UA1 and UA2 experiments at CERN's SPS proton-antiproton Collider, still the focus of world attention despite having taken no new data since last year

  7. Clinical and genetic study of a juvenile-onset Huntington disease

    Directory of Open Access Journals (Sweden)

    HAO Ying

    2012-06-01

    Full Text Available Background Huntington's disease (HD is an autosomal dominant hereditary progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dementia, cognitive and affective impairment. There are selective neural cell loss and atrophy in the caudate and putamen. Dr. George Huntington firstly described the disease accurately and insightfully, which led to a widespread recognition of the inherited chorea that now bears his name. Huntington disease gene (IT15 locus on chromosome 4p16.3, and encompasses 67 exons with a trinucleotide repeat (CAG in the first exon. The CAG repeat length is highly polymorphic in the population and expanded on at least one chromosome of individuals with HD. Clinically, patient with HD are often onset in adulthood. Juvenile-onset HD is relatively rare. Adult-onset HD patients usually have a CAG expansion from 40 to 55 whereas those with juvenile-onset greater than 60 which are often inherited from the father. We investigated the clinical features of a juvenile-onset case with Huntington disease and dynamic mutation of his family. Methods The CAG repeats of IT15 gene were detected using polymerase chain reaction and capillary electrophoresis in 115 individuals with preliminary diagnosis as Huntington disease. The repeat numbers of some samples carried expanded or intermediate alleles were verified by the pMD18-T vector clone sequencing. Results Fragment analysis showed that one juvenile-onset case presenting with cognitive dysfunction and hypokinesis carried 15/68 CAG repeats of IT15. His father carried 17/37 and mother carried 15/17. Conclusion 1 The juvenile-onset case of HD presented with different clinical features compared with adult-onset cases. The typical signs of adult-onset cases include progressive chorea, rigidity and dementia. The most common sign of juvenile-onset Huntington disease is cognitive decline. 2 The dynamic mutation of IT15 gene expansion of the CAG repeats in the

  8. Clinical pathological and genetic analysis of 2 cases of mitochondrial myopathy presented as acute motor axonal neuropathy

    Directory of Open Access Journals (Sweden)

    Hou-min YIN

    2014-06-01

    Full Text Available Background The main clinical manifestations of mitochondrial myopathy are chronic limb weakness and muscular soreness. Subclinical peripheral nerve injury is also reported, but acute axonal neuropathy.like syndrome concurrent with lactic acidosis is rare. In this paper the clinical features of 2 patients presenting as acute lactic acidosis and sudden muscle weakness were analyzed. Pathological changes and genetic mutations were detected.  Methods Electromyography (EMG and muscle biopsy were performed. Modified Gomori trichrome (MGT and succinodehydrogenase (SDH staining were used to identify pathological changes. Changes of ultra microstructure of muscular tissue were observed under electron microscope. Mitochondrial DNA (mtDNA full length sequencing was performed using 24 pairs of partially overlapping primers.  Results EMG showed a coexistence of neurogenic and myogenic changes. Dramatic decrease of motor nerve amplitude and moderately reduced sensory nerve amplitude were observed but nerve conduction velocity was normal in both patients. Impressive ragged red fibers were seen on MGT staining. Electron microscope showed dramatic mitochondrial abnormalities in Case 1 and paracrystaline inclusions in Case 2. mtDNA sequencing showed 3243A > G mutation in Case 1 and 8344A > G mutation in Case 2. Conclusions Mitochondrial myopathy can present as metabolic crisis like acute lactic acidosis, dyspnea and acute motor axonal neuropathy.like syndrome. It is a life.threatening phenotype that needs more attention. doi: 10.3969/j.issn.1672-6731.2014.06.007

  9. Predicting the Pathogenic Potential of BRCA1 and BRCA2 Gene Variants Identified in Clinical Genetic Testing

    Directory of Open Access Journals (Sweden)

    Clare Brookes

    2015-05-01

    Full Text Available Objectives: Missense variants are very commonly detected when screening for mutations in the BRCA1 and BRCA2 genes. Pathogenic mutations in the BRCA1 and BRCA2 genes lead to an increased risk of developing breast, ovarian, prostate and/or pancreatic cancer. This study aimed to assess the predictive capability of in silico programmes and mutation databases in assisting diagnostic laboratories to determine the pathogenicity of sequence-detectable mutations. Methods: Between July 2011 and April 2013, an analysis was undertaken of 13 missense BRCA gene variants that had been detected in patients referred to the Genetic Health Services New Zealand (Northern Hub for BRCA gene analysis. The analysis involved the use of 13 in silico protein prediction programmes, two in silico transcript analysis programmes and the examination of three BRCA gene databases. Results: In most of the variants, the analysis showed different in silico interpretations. This illustrates the interpretation challenges faced by diagnostic laboratories. Conclusion: Unfortunately, when using online mutation databases and carrying out in silico analyses, there is significant discordance in the classification of some missense variants in the BRCA genes. This discordance leads to complexities in interpreting and reporting these variants in a clinical context. The authors have developed a simple procedure for analysing variants; however, those of unknown significance largely remain unknown. As a consequence, the clinical value of some reports may be negligible.

  10. Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

    Science.gov (United States)

    Harper, Joyce C; Geraedts, Joep; Borry, Pascal; Cornel, Martina C; Dondorp, Wybo; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather; Soini, Sirpa; Spits, Claudia; Veiga, Anna; Vermeesch, Joris Robert; Viville, Stéphane; de Wert, Guido; Macek, Milan

    2013-11-01

    In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide

  11. A GENETIC STUDY TO DIFFERENTIAL HA/CA MRSA ISOLATED FROM CLINICAL CASES IN IRAQ HOSPITALS.

    Directory of Open Access Journals (Sweden)

    ISRAA MOHAMED SAFI AL- KADMY

    2013-01-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA has been a major cause of nosocomial infections since the 1960s . Currently, MRSA is divided into two subgroups: the healthcare associated MRSA (HA-MRSA and community associated MRSA(CA-MRSA, CA-MRSA infections have been increasing. The most common of these infections present in soft skin. The aim of this study to different between CA and HA MRSA in clinical isolates of Baghdad hospitals.Methods: clinical isolates were collected from patients with different infections, Simple laboratory testing followed by the complementary API Staph, followed by antibiotic sensitivity and D-test, and finally by using PCR technique, detection of this genes : mecA, PVL, SCCmec IV and V .Results: A total of 105 S.aureus found 104 methicillin-resistant Staphylococcus aureus (MRSA strains, after a D-test , S.aureus divided to two group: CA and HA –MRSA, where the ratio of CA 18(17.1% out of 105 isolates, while HA reached 87(82.8%. MRSA was characterized by PCR amplification mecA gene, 104(99.04% isolates out of 105 gave positive result, all isolates of HA carry mecA gene, while 17 out of 18 isolates of CA carry mecA gene which was CA-MRSA and one isolates was CA-MSSA . All isolates 18(100% of CA gave positive result in risk factors PVL gene, while for detection of SCCmec IV 17 (94.4% out of 18 isolates of CA gave positive result, and finally two isolates of CA-MRSA gave positive result in SCCmec V gene .Conclusions: This is the first report in Iraq for the emergence of CA isolates especially CA-MRSA which is responsible for the majority of infection in soft tissue and skin abscesses , are likely to be sensitive to clindamycin.

  12. Genetic and clinical characterization of canine leishmaniasis caused by Leishmania (Leishmania) infantum in northeastern Argentina.

    Science.gov (United States)

    Barroso, Paola A; Nevot, M Cecilia; Hoyos, Carlos L; Locatelli, Fabricio M; Lauthier, Juan J; Ruybal, Paula; Cardozo, Rubén M; Russo, Pablo D; Vassiliades, Carola N; Mora, María C; Estévez, J Octavio; Hashiguchi, Yoshihisa; Korenaga, Masataka; Basombrío, Miguel A; Marco, Jorge D

    2015-10-01

    Leishmaniases comprise zoonotic diseases caused by protozoan flagellates of the Leishmania genus. They are endemic to South America, and the visceral form has been recently reported in Argentina. Dogs can play different roles in the Leishmania transmission cycles, depending mainly on the species of parasite involved. Here we focused on the clinical characterization of canine leishmaniasis (CanL) in Northeast Argentina and on the molecular typing of its etiological agent. The nested polymerase chain reaction and sequence analysis of the Leishmania cytochrome b (cyt b) gene was performed on DNA templates purified from lymph nodes, bone marrow or spleen aspirates obtained from 48 dogs previously diagnosed by the observation of Leishmania amastigotes on smears from these aspirates. Their clinical and epidemiological data were also recorded. Systemic abnormalities were observed in 46 subjects (95.8%), most frequently lymphadenopathy, and emaciation (89.6 and 75%). Furthermore, 87% also presented tegumentary abnormalities, such as alopecia (54.2%) or secondary skin lesions (47.9%), among others. Twenty three dogs were positive for cyt b amplification. The sequence analysis showed the presence of two genotypes, LiA1 and LiA2, assigned to Leishmania (Leishmania) infantum, with 99.9 and 100% homology with the reference strain MHOM/TN/80/IPT1 respectively. LiA1 was identified in 18 cases (78.3%) and LiA2 in five (21.7%). Two cyt b variants of L. (L.) infantum were incriminated as the causative agents of CanL cases from three cities: Posadas, Garupá, and Ituzaingó. All three cities are located in the northeastern area of the country, where these parasites seem to be spreading in urban areas. PMID:26277067

  13. Tentative clinical diagnosis of Lujan-Fryns syndrome--A conglomeration of different genetic entities?

    Science.gov (United States)

    Hackmann, Karl; Rump, Andreas; Haas, Stefan A; Lemke, Johannes R; Fryns, Jean-Pierre; Tzschach, Andreas; Wieczorek, Dagmar; Albrecht, Beate; Kuechler, Alma; Ripperger, Tim; Kobelt, Albrecht; Oexle, Konrad; Tinschert, Sigrid; Schrock, Evelin; Kalscheuer, Vera M; Di Donato, Nataliya

    2016-01-01

    The clinical diagnosis of Lujan-Fryns syndrome (LFS) comprises X-linked intellectual disability (XLID) with marfanoid habitus, distinct combination of minor facial anomalies and nasal speech. However the definition of syndrome was significantly broadened since the original report and implies ID with marfanoid habitus. Mutations of three genes (MED12, UPF3B, and ZDHHC9) have been reported in "broadly defined" LFS. We examined these genes in 28 individuals with a tentative clinical diagnosis of LFS but we did not identify any causative mutation. By molecular karyotyping we detected other disorders, i.e., Phelan-McDermid syndrome and 16p11.2 microduplication, each in one patient. One affected individual was carrier of a different recurrent duplication on 16p11.2 that has been reported several times to the DECIPHER and ISCA databases in individuals with autism, intellectual disability (ID), and developmental delay. It may represent a new duplication syndrome. We also identified previously unreported de novo duplication on chromosome 12p13.31 which we considered to be disease-causing. X-exome sequencing of four individuals revealed private or non-recurrent mutations in NKAP and LAS1L in one patient each. While LFS is defined as a form of XLID, there seem to be various conditions that have rather similar phenotypes. Therefore, the combination of ID and marfanoid habitus in a male patient is not sufficient for the diagnosis of LFS. We suggest that the diagnosis of LFS in patients with ID and marfanoid habitus should be made only in presence of specific facial features, nasal speech and obvious X-linked segregation of the disorder or an unambiguously pathogenic mutation in the MED12. PMID:26358559

  14. Clinical and genetic predictors of response to narrowband ultraviolet B for the treatment of chronic plaque psoriasis.

    LENUS (Irish Health Repository)

    Ryan, C

    2012-02-01

    BACKGROUND: There is considerable variability in the number of exposures of narrowband ultraviolet B (NB-UVB) needed to clear psoriasis and in the duration of remission. OBJECTIVES: We assessed clinical parameters as predictors of the number of exposures needed to clear psoriasis and of the duration of remission. The influence of genetic polymorphisms of the vitamin D receptor (VDR) on treatment response was also evaluated. METHODS: This was a prospective study of 119 patients with chronic plaque psoriasis treated with NB-UVB until clearance was achieved. They were then followed for up to 1 year or until relapse occurred. The frequency of the Fok1, Apa1, Bsm1, Taq1 and rs4516035 polymorphisms of the VDR gene was assessed in 93 of the 119 patients. RESULTS: Of the 119 patients, 105 completed the course of phototherapy. Using an intention to treat analysis, 83% of the initial cohort (99 of 119 patients) achieved clearance, in a median of 26 exposures (interquartile range 19-35) with a median remission duration of 16 weeks (interquartile range 9-22). Factors significantly associated with a lower number of exposures to clearance included a lower baseline Psoriasis Area and Severity Index (P = 0.004), lower baseline Dermatology Life Quality Index (P = 0.047), female sex (P = 0.043), lower body weight (P = 0.008), and a higher number of previous courses of TL-01 (P = 0.005). The only clinical factor influencing remission duration was number of exposures (P = 0.0009), with a decreased remission duration in those who required a greater number of exposures to clear. The Taq1 VDR polymorphism (rs731236) also significantly predicted remission duration (P = 0.038). Patients homozygous for the C allele, which is associated with decreased activity of the VDR, had a shorter remission duration than those heterozygous for the allele (P = 0.026) and those homozygous for the T allele (P = 0.013). CONCLUSIONS: This study highlights the fact that both genetic and clinical parameters

  15. Consensus conferences

    DEFF Research Database (Denmark)

    Nielsen, Annika Porsborg; Lassen, Jesper

    , the differing perceptions are each in their own way rooted in an argument for democratic legitimacy. We therefore argue that national interpretations of consensus conferences, and of their ability to functions as a tool for public participation, depend to a great extent on the dominant ideals of...... democratic legitimacy embedded in national political cultures....

  16. Conference Hopes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Annual conference outlines tasks for 2010 to solidify China’s economic recovery through rational investment and increasing consumptionc hina will adhere to a consistent and stable economic strategy, putting in place a proactive fiscal policy and an accommodative monetary policy for the 2010 fiscal year-the macro-economic course mapped out during China’s Central

  17. Conference summaries

    International Nuclear Information System (INIS)

    The papers presented at this conference cover the fields of thermalhydraulics, nuclear plant design and operation, licensing, decontamination, restoration and dismantling of nuclear power facilities, services to the nuclear industry, new applications of nuclear technology, reactor physics and fuel cycles, accelerator-breeders, fusion research and lasers

  18. Preclinical Biosafety Evaluation of Genetically Modified Human Adipose Tissue-Derived Mesenchymal Stem Cells for Clinical Applications to Brainstem Glioma.

    Science.gov (United States)

    Choi, Seung Ah; Yun, Jun-Won; Joo, Kyeung Min; Lee, Ji Yeoun; Kwak, Pil Ae; Lee, Young Eun; You, Ji-Ran; Kwon, Euna; Kim, Woo Ho; Wang, Kyu-Chang; Phi, Ji Hoon; Kang, Byeong-Cheol; Kim, Seung-Ki

    2016-06-15

    Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC.sTRAIL. At first, we injected stereotactically low (1.2 × 10(5) cells/18 μL), medium (2.4 × 10(5)/18 μL), or high dose (3.6 × 10(5)/18 μL) of hAT-MSC.sTRAIL into the brainstems of immunodeficient mice reflecting the plan of the future clinical trial. Local toxicity, systemic toxicity, secondary tumor formation, and biodistribution of hAT-MSC.sTRAIL were investigated. Next, presence of hAT-MSC.sTRAIL was confirmed in the brain and major organs at 4, 9, and 14 weeks in brainstem glioma-bearing mice. In the 15-week subchronic toxicity test, no serious adverse events in terms of body weight, food consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology were observed. In the 26-week tumorigenicity test, hAT-MSC.sTRAIL made no detectable tumors, whereas positive control U-87 MG cells made huge tumors in the brainstem. No remaining hAT-MSC.sTRAIL was observed in any organs examined, including the brainstem at 15 or 26 weeks. In brainstem glioma-bearing mice, injected hAT-MSC.sTRAIL was observed, but gradually decreased over time in the brain. The mRNA of human specific GAPDH and TRAIL was not detected in all major organs. These results indicate that the hAT-MSC.sTRAIL could be applicable to the future clinical trials in terms of biosafety. PMID:27151205

  19. Biofilm synthesis and its relationship with genetic characteristics in clinical methicillin-resistant staphylococci

    Directory of Open Access Journals (Sweden)

    Nikolaos Giormezis

    2015-09-01

    Full Text Available Staphylococcus aureus can cause a broad range of infections, including skin infections, pneumonia and bacteraemia. Coagulase-negative staphylococci (CNS, mainly S. epidermidis, have also emerged as important pathogens, especially in immunocompromised patients or those with prosthetic devices, such as intravascular catheters or biomaterials. Of great importance in the initiation of these infections is the ability of staphylococci to adhere to various surfaces, such as host tissues and prosthetic devices and to form biofilm. The staphylococcal adhesins are encoded by a number of genes such as fnbA (S. aureus fibronectin binding protein A, sasG (S. aureus surface protein G, aap (S. epidermidis accumulation associated protein, bhp (Bap homologue protein and fbe (fibrinogen binding protein epidermidis. In this study, 106 methicillin-resistant S. aureus (MRSA, 145 methicillin-resistant S. epidermidis (MRSE and 70 non-epidermidis methicillin-resistant CNS (MR-CNS; 58 S. haemolyticus, 10 S. hominis and two S. lugdunensis were compared in terms of biofilm formation, antimicrobial resistance, clonal distribution and adhesin genes carriage. Isolates were classified into pulsotypes by PFGE and assigned to sequence types by MLST. In total, 121/321 isolates (37.7% produced biofilm and 219 (68.2% carried ica operon. The majority was multidrug resistant (94.7% and carried one or more adhesin genes. MRSE and all other MR-CNS prevailed in biofilm formation (P < 0.001 and antimicrobial resistance (P < 0.05 as compared to MRSA. MRSE also prevailed in ica carriage compared to the other methicillin-resistant staphylococci (P ≤ 0.007 Among MRSE, isolates from bacteraemias prevailed in biofilm formation (P = 0.031, whereas, strains from prosthetic device-associated infections carried more frequently aap (P = 0.003. Even though PFGE showed genetic diversity among MRSE, MLST revealed three major clones (ST2, ST5, ST16. MRSA isolates were less diverse, with five PFGE

  20. A South African family with oculopharyngeal muscular dystrophy: Clinical and molecular genetic characteristics.

    Science.gov (United States)

    Schutte, Clara Maria; Dorfling, Cecelia M; van Coller, Riaan; Honey, Engela M; van Rensburg, Elizabeth Jansen

    2015-07-01

    Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria, South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this family has been described previously in families from Uruguay and Mexico as a founder effect. To our knowledge, this is the first report of an SA Afrikaner family with molecularly confirmed OPMD. The proband, a 64-year-old woman, presented to the neurology outpatient department at Steve Biko Academic Hospital, Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD. Four patients were interviewed and examined clinically, and electromyographic studies were performed. Molecular analysis of the PABPN1 gene was performed by polymerase chain reaction amplification and direct sequencing of exon 1 in three of the patients. Patients presented with ptosis, external ophthalmoplegia, dysphagia, dysarthria and mild proximal weakness. High foot arches and absent ankle reflexes raised the possibility of peripheral neuropathy, but electromyography showed only mildly low sensory amplitudes, and myopathic units in two patients. PMID:26428746

  1. MERRF: Clinical features, muscle biopsy and molecular genetics in Brazilian patients.

    Science.gov (United States)

    Lorenzoni, Paulo José; Scola, Rosana H; Kay, Cláudia S Kamoi; Arndt, Raquel C; Silvado, Carlos E; Werneck, Lineu C

    2011-05-01

    Myoclonic epilepsy with ragged red fibers (MERRF) is a mitochondrial disease that is characterized by myoclonic epilepsy with ragged red fibers (RRF) in muscle biopsies. The aim of this study was to analyze Brazilian patients with MERRF. Six patients with MERRF were studied and correlations between clinical findings, laboratory data, electrophysiology, histology and molecular features were examined. We found that blood lactate was increased in four patients. Electroencephalogram studies revealed generalized epileptiform discharges in five patients and generalized photoparoxysmal responses during intermittent photic stimulation in two patients. Muscle biopsies showed RRF in all patients using modified Gomori-trichrome and succinate dehydrogenase stains. Cytochrome c oxidase (COX) stain analysis indicated deficient activity in five patients and subsarcolemmal accumulation in one patient. Molecular analysis of the tRNA(Lys) gene with PCR/RFLP and direct sequencing showed the A8344G mutation of mtDNA in five patients. The presence of RRFs and COX deficiencies in muscle biopsies often confirmed the MERRF diagnosis. We conclude that molecular analysis of the tRNA(Lys) gene is an important criterion to help confirm the MERRF diagnosis. Furthermore, based on the findings of this study, we suggest a revision of the main characteristics of this disease. PMID:21303704

  2. The clinical and genetic correlates of MRI findings in myotonic dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Bachmann, G. [Neuromuscular and Genetic Research Group, Department of Radiology, Justus Liebig University, Giessen (Germany); Damian, M.S. [Department of Neurology, University of Giessen (Germany); Koch, M. [Department of Human Genetics, University of Marburg (Germany); Schilling, G. [Department of Psychiatry, University of Giessen (Germany); Fach, B. [Department of Neurology, University of Giessen (Germany); Stoeppler, S. [Department of Neurology, University of Giessen (Germany)

    1996-10-01

    Amplification of an unstable CTG trinucleotide repeat sequence in a protein kinase gene on chromosome 19 has recently been recognised as the molecular basis of myotonic dystrophy (DM), a multisystem disorder with a wide spectrum of muscular and extramuscular manifestations. The CTG expansion of 40 patients was assessed by direct genotype analysis of the white blood cell DNA and correlated with MRI of the brain and muscles, and with functional clinical data. Cerebral pathology on MRI consisted of diffuse atrophy (68 %), subcortical white matter lesions (65 %), wide Virchow-Robin spaces (38 %) and thickening of the skull (35 %). Cerebral atrophy and extent of white matter disease correlated significantly with mental retardation, duration of disease and CTG fragment amplification. MRI of the muscular system showed fatty degeneration of different degrees in neighbouring muscles causing a mosaic pattern of the thigh in 38 % and the calf in 44 %. Muscular changes on MRI were strongly correlated with muscular impairment but less strongly with CTG expansion. Changes on MRI reflect the stage of development of tissue pathology in DM, modified by defect of the DM gene. Pathology on MRI is strongly correlated with functional deficits. (orig.). With 8 figs., 3 tabs.

  3. The clinical and genetic correlates of MRI findings in myotonic dystrophy

    International Nuclear Information System (INIS)

    Amplification of an unstable CTG trinucleotide repeat sequence in a protein kinase gene on chromosome 19 has recently been recognised as the molecular basis of myotonic dystrophy (DM), a multisystem disorder with a wide spectrum of muscular and extramuscular manifestations. The CTG expansion of 40 patients was assessed by direct genotype analysis of the white blood cell DNA and correlated with MRI of the brain and muscles, and with functional clinical data. Cerebral pathology on MRI consisted of diffuse atrophy (68 %), subcortical white matter lesions (65 %), wide Virchow-Robin spaces (38 %) and thickening of the skull (35 %). Cerebral atrophy and extent of white matter disease correlated significantly with mental retardation, duration of disease and CTG fragment amplification. MRI of the muscular system showed fatty degeneration of different degrees in neighbouring muscles causing a mosaic pattern of the thigh in 38 % and the calf in 44 %. Muscular changes on MRI were strongly correlated with muscular impairment but less strongly with CTG expansion. Changes on MRI reflect the stage of development of tissue pathology in DM, modified by defect of the DM gene. Pathology on MRI is strongly correlated with functional deficits. (orig.). With 8 figs., 3 tabs

  4. Should pre-implantation genetic screening be implemented to routine clinical practice?

    Science.gov (United States)

    Orvieto, Raoul; Shuly, Yulia; Brengauz, Masha; Feldman, Baruch

    2016-06-01

    The utilization of trophectoderm biopsy combined with comprehensive chromosome screening (CCS) tests for embryonic aneuploidy was recently suggested to improve IVF outcome, however, not without criticisms. Since mosaicism has been reported in as high as 90% of blastocyst-stage embryos, we aimed to evaluate the accuracy of trophectoderm multiple biopsies using next-generation sequencing (NGS). Eight top quality blastocysts underwent three trophectoderm biopsies each, followed by NGS. In four blastocysts, the rest of the embryo, which included the inner cell mass, was also analyzed. Five of the 24 (20.8%) trophectoderm biopsies revealed inconclusive results, while 4 (16.6%) demonstrated embryonic mosaicism. Overall, 10 (35.7%) of the 28 (24 trophectoderms and 4 inner cell masses) biopsies revealed mosaicism or inconclusive results. Our preliminary observations contribute to the ongoing discussion on the unrestricted clinical adoption of PGS, suggesting, that until proper evaluation of its effectiveness and cost-effectiveness will be provided, PGS should be offered only under study conditions, and with appropriate informed consents. PMID:26872945

  5. DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features.

    Science.gov (United States)

    Arribas, Alberto J; Rinaldi, Andrea; Mensah, Afua A; Kwee, Ivo; Cascione, Luciano; Robles, Eloy F; Martinez-Climent, Jose A; Oscier, David; Arcaini, Luca; Baldini, Luca; Marasca, Roberto; Thieblemont, Catherine; Briere, Josette; Forconi, Francesco; Zamò, Alberto; Bonifacio, Massimiliano; Mollejo, Manuela; Facchetti, Fabio; Dirnhofer, Stephan; Ponzoni, Maurilio; Bhagat, Govind; Piris, Miguel A; Gaidano, Gianluca; Zucca, Emanuele; Rossi, Davide; Bertoni, Francesco

    2015-03-19

    Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation. PMID:25612624

  6. Design of the BRISC study : a multicentre controlled clinical trial to optimize the communication of breast cancer risks in genetic counselling

    NARCIS (Netherlands)

    Ockhuysen-Vermey, Caroline F.; Henneman, Lidewij; van Asperen, Christi J.; Oosterwijk, Jan C.; Menko, Fred H.; Timmermans, Danielle R. M.

    2008-01-01

    Background: Understanding risks is considered to be crucial for informed decision-making. Inaccurate risk perception is a common finding in women with a family history of breast cancer attending genetic counseling. As yet, it is unclear how risks should best be communicated in clinical practice. Thi

  7. Determinants of HbA1c in nondiabetic Dutch adults : genetic loci and clinical and lifestyle parameters, and their interactions in the lifelines cohort study

    NARCIS (Netherlands)

    Jansen, Hanneke; Stolk, R.P.; Nolte, I.M.; Kema, I.P.; Wolffenbuttel, B.H.; Snieder, H.

    2013-01-01

    Jansen H, Stolk RP, Nolte IM, IP Kema, Wolffenbuttel BHR, Snieder H (University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands). Determinants of HbA1c in nondiabetic Dutch adults: genetic loci and clinical and lifestyle parameters, and their interactions in the LifeLin

  8. A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis patients: clinical and genetic features

    Directory of Open Access Journals (Sweden)

    Fernandez Bridget A

    2012-08-01

    . Conclusion The proportion of familial cases in our cohort is higher than any previously reported estimate and we suggest that this is due to the fact that Newfoundland cohort is ethnically homogeneous and drawn from a founder population. In our patient collection, diagnosis with IPF prior to age 45 years predicted familial disease. In two of the three TERT mutation families, the pedigree appearance is consistent with genetic anticipation. In the other 25 FPF families negative for mutations in known PF genes, we did not identify other telomerase associated medical problems (bone marrow dysfunction, cirrhosis and we hypothesize that there are novel PF genes segregating in our population.

  9. [Muscular dystrophy due to mutations in anoctamin 5: clinical and molecular genetic findings].

    Science.gov (United States)

    Deschauer, M; Joshi, P R; Gläser, D; Hanisch, F; Stoltenburg, G; Zierz, S

    2011-12-01

    Recessive mutations in the anoctamin 5 (ANO5) gene have been recently identified in families with limb girdle muscular dystrophy (LGMD2L) and distal non-dysferlin Miyoshi myopathy. Anoctamin 5 is supposed to be a putative calcium-activated chloride channel. We report five German patients (four index patients) with muscle dystrophy due to mutations in the ANO5 gene. Sequencing of the ANO5 exons 5, 13 and 20 was performed to screen for a common c.191dupA mutation and two other reported mutations (c.1295C>G and p.R758C). The whole coding region of the ANO5 gene was sequenced to identify new mutations. Phenotypically, three patients showed LGMD and one patient Miyoshi type distal myopathy. One sibling had asymptomatic hyperCKemia. The age at onset was 64, 38 and 40 years in patients with LGMD and 23 years in the patient with distal myopathy. The four symptomatic patients showed remarkable asymmetric muscle involvement. There was marked CK elevation (11 to 30 times). Electron microscopy showed multifocal gaps in the sarcolemmal membrane. All patients harboured the common c.191dupA mutation in at least one allele. Two patients with LGMD were homozygous and the third patient and his asymptomatic sister were compound heterozygous for the c.191dupA mutation and a novel p.T548I mutation. The patient with distal myopathy harboured the p.R758C mutation in the second allele. Mutations in the ANO5 gene seem to be a relatively common cause of muscular dystrophy in Germany. Cases with late onset or asymptomatic hyperCKemia can occur. Clinically, asymmetric manifestation is typical. PMID:21739273

  10. Clinical and genetic study on schizophrenia using cranial computed tomography (CT)

    International Nuclear Information System (INIS)

    Eighty patients with schizophrenia and 45 medical controls were examined by cranial computed tomography (CT). The schizophrenic group showed statistically significant differences with more severe widening of the lateral ventricles, the third ventricle and Sylvius fissure, and more severe atrophy in the frontal and parietal cortex than controls. The schizophrenic cases were classified into patients with or without any hereditary trait. The former group was further subdivided into 3 groups, i.e., patients with a horizontal transmission who have sibling with schizophrenia, patients with a vertical transmission who have parents or offspring with schizophrenia, and patients with both familial traits. More severe widening of the Sylvius fissure was seen in patients with a hereditary trait than in those without. The schizophrenic group, with a hereditary trait, demonstrated significantly longer duration of hospitalization, more negative symptoms and more severe widening of the lateral ventricles and the third ventricle in comparison with the schizophrenic group without any hereditary trait. The degree of the widening of the lateral ventricles seen in the subgroup with a horizontal transmission did not correlate with any other findings in CT. This means that the change is specific to this group. No significant correlation was seen between such clinical items as age and duration of illness, and widening of the lateral ventricles in the subgroup with a horizontal transmission. All this evidence implies that more advanced widening of the lateral ventricles and more serious negative symptoms exist constantly and not progressively at the point of onset in the subgroup with a horizontal transmission. (J.P.N.)

  11. Microbicides 2006 conference

    Directory of Open Access Journals (Sweden)

    McGowan Ian

    2006-10-01

    Full Text Available Abstract Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23–26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities.

  12. Antagonistic Pleiotropy at the Human IL6 Promoter Confers Genetic Resilience to the Pro-Inflammatory Effects of Adverse Social Conditions in Adolescence

    OpenAIRE

    Cole, Steven W.; Arevalo, Jesusa M. G.; Manu, Kavya; Telzer, Eva H; Kiang, Lisa; Bower, Julienne E.; Irwin, Michael R.; Fuligni, Andrew J.

    2011-01-01

    The authors tested the evolutionary genetic hypothesis that the functional form of an asymmetrically risky Gene × Environment interaction will differ as a function of age-related antagonistic pleiotropy (i.e., show opposite effects in young vs. old individuals). Previous studies have identified a polymorphism in the human IL6 promoter (rs1800795; IL6 –174 G/C) that interacts with adverse socioenvironmental conditions to promote chronic inflammation in older adults (elevated C-reactive protein...

  13. Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.

    Directory of Open Access Journals (Sweden)

    Olga Gorlova

    2011-07-01

    Full Text Available The aim of this study was to determine, through a genome-wide association study (GWAS, the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc. We considered limited (lcSSc and diffuse (dcSSc cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA, and anti-topoisomerase I (ATA. Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12, OR = 0.75. Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6, OR = 1.15 and rs11047102 in SOX5 gene (P = 1.39×10(-7, OR = 1.36 showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61, OR = 2.48, in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76, OR = 8.84, and in NOTCH4 with ACA P = 8.84×10(-21, OR = 0.55 and ATA (P = 1.14×10(-8, OR = 0.54. We have identified three new non-HLA genes (IRF8, GRB10, and SOX5 associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.

  14. Features of 152 families eligible for the investigation of mutations in BRCA1 / 2, evaluated Onco genetics unit Clinics Hospital

    International Nuclear Information System (INIS)

    Full text: The aim of this study is to contribute to the characterization of familial breast cancer in our country. Patients and methods. We analyzed 152 families referred to the Hospital Unit Onco genetics Clinic, who had 3 or more cases of breast cancer (C M)(at least one diagnosed before age 50 years) (n = 92)or 2 cases with some sub-criterion (paternal transmission, C M bilateral C M male, ovarian cancer (O C), Ashkenazi Jewish ancestry, a case diagnosed before 40 years) (n = 47)or 4 or more cases without regard to age at diagnosis (n = 4)or an single case diagnosed before age 35 (n = 9). The clinical data collection was conducted onco genetics the query was entered in which, among others, the presence or absence of nongenetic risk factors, personal and family history of breast, ovarian and other tumors and age of diagnosis. Results. 152 cases were selected indices, carrying 148 C M (bilateral n = 29)and 4 CO. The median age at diagnosis of C M developed in these patients was 48 years (range: 25-54). Twenty-three of the 151 patients had a second tumor extra mammary (ovary n = 7; melanoma n = 2, n = 3 cervix, colon n = 4, n = 1 sarcoma, ENT = 1, = 1 pancreas, kidney = 2, CBP = 1, esophagus = 1). Among the relatives of the relevant parent branch were 329 C M (25 bilateral, 2 male)diagnosed before 50 years in more than 60 % of cases and 22 ovarian cancers. Comparing the frequency of different tumor locations both branches parents. In the relevant parent branch, and the prevalence of C M and CO documented a higher frequency of prostate, stomach, pancreas and melanoma. It was possible to obtain information He r2 tumor expression, estrogen receptor (E R) and progesterone receptor (P R) in 25 patients, finding that 10 patients (0.40)had He r2 overexpression, 11 (0.46 R E and / / or P R positive, HER2 negative and 4 E R, P R and He r2 negative (0.16). Conclusions. The characteristics of the families studied, including the frequency of tumors extramamarios agrees with

  15. Clinical biological and genetic heterogeneity of the inborn errors of pulmonary surfactant metabolism.

    Science.gov (United States)

    Tredano, M; De Blic, J; Griese, M; Fournet, J C; Elion, J; Bahuau, M

    2001-02-01

    Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus to which a range of physical (surface-active properties) and immune functions has been assigned. This complex consists of a surface-active lipid layer (consisting mainly of phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly hydrophobic surfactant proteins B (SP-B) and C (SP-C) as well as collectins SP-A and SP-D, which were shown to have specific structural, metabolic, or immune properties. Inborn or acquired abnormalities of the surfactant, qualitative or quantitative in nature, account for a number of human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases has been characterized by periodic acid-Schiff-positive material filling the alveoli. From this heterogeneous nosologic group, at least two discrete entities presently emerge. The first is the SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which represents an autosomal recessive Mendelian entity linked to the SFTPB gene (MIM 1786640). The disease usually generally entails neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed. The second is alveolar proteinosis, characterized by the storage of a mixed protein and lipid material, which constitutes a relatively heterogeneous clinical and biological syndrome, especially with regard to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models, with a targeted mutation of the gene encoding granulocyte macrophage colony-stimulating factor (GM-CSF) (Csfgm) or the beta subunit of its receptor (II3rb1) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage is a key player. Apart from SP-B deficiency, in which a near-consensus diagnostic

  16. Hunter disease eClinic: interactive, computer-assisted, problem-based approach to independent learning about a rare genetic disease

    Directory of Open Access Journals (Sweden)

    Moldovan Laura

    2010-10-01

    Full Text Available Abstract Background Computer-based teaching (CBT is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II. Aim To develop interactive teaching software functioning as a virtual clinic for the management of MPS II. Implementation and Results The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca, was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available. Conclusions The

  17. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity.

    Science.gov (United States)

    Kwiterovich, Peter O

    2002-10-17

    increased levels of free fatty acids in plasma, increased flux of free fatty acids back to the liver, enhanced production of TGs, decreased proteolysis of apo B-100, and increased VLDL production. Decreased removal of postprandial TGs often accompanies these metabolic abnormalities. Genes regulating the expression of the major players in this metabolic cascade, such as LPL, cholesterol ester transfer protein, and hepatic lipase, can modulate the expression of small, dense LDL but these are not the major defects. New candidates for major gene effects have been identified on chromosome 1. Regardless of their fundamental causes, small, dense LDL (compared with normal LDL) particles have a prolonged residence time in plasma, are more susceptible to oxidation because of decreased interaction with the LDL receptor, and enter the arterial wall more easily, where they are retained more readily. Small, dense LDL promotes endothelial dysfunction and enhanced production of procoagulants by endothelial cells. Both in animal models of atherosclerosis and in most human epidemiologic studies and clinical trials, small, dense LDL (particularly when present in increased numbers) appears more atherogenic than normal LDL. Treatment of patients with small, dense LDL particles (particularly when accompanied by low HDL and hypertriglyceridemia) often requires the use of combined lipid-altering drugs to decrease the number of particles and to convert them to larger, more buoyant LDL. The next critical step in further reduction of CAD will be the correct diagnosis and treatment of patients with small, dense LDL and the dyslipidemia that accompanies it. PMID:12419479

  18. Conference summaries

    International Nuclear Information System (INIS)

    This volume contains summaries of 28 papers presented at the 27. conference of the Canadian Nuclear Association. These papers discuss the general situation of the Canadian nuclear industry and the CANDU reactor; dialogue with the public; the International Atomic Energy Agency; and economic goals and operating lessons. It also contains summaries of 70 papers presented at the 8. conference of the Canadian Nuclear Society, which discuss plant life extension; safety and the environment; reactor physics; thermalhydraulics; risk assessment; the CANDU spacer location and repositioning project; CANDU operations; safety research after Chernobyl; fuel channels; and nuclear technology developments. The individual papers are also available in INIS-mf--13673 (CNA), and INIS-mf--12909 (CNS). (L.L.)

  19. Conference information

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Thermag Ⅳ- The 4th International Conference on Magnetic Refrigeration at Room Temperature of IIR Refrigeration technology is widely used today. However, traditional vapor compression/expansion refrigeration technology has some disadvantages, such as low conversion efficiency of vapor compressor, and emission of the ozonosphere depletion gas and greenhouse effect gas, etc. Magnetic refrigeration is a new cooling technology with huge potential application prospect, characterized by high efficiency, energy saving and environmental friendly.

  20. Genetic dissection of a TIR-NB-LRR locus from the wild North American grapevine species Muscadinia rotundifolia identifies paralogous genes conferring resistance to major fungal and oomycete pathogens in cultivated grapevine.

    Science.gov (United States)

    Feechan, Angela; Anderson, Claire; Torregrosa, Laurent; Jermakow, Angelica; Mestre, Pere; Wiedemann-Merdinoglu, Sabine; Merdinoglu, Didier; Walker, Amanda R; Cadle-Davidson, Lance; Reisch, Bruce; Aubourg, Sebastien; Bentahar, Nadia; Shrestha, Bipna; Bouquet, Alain; Adam-Blondon, Anne-Françoise; Thomas, Mark R; Dry, Ian B

    2013-11-01

    The most economically important diseases of grapevine cultivation worldwide are caused by the fungal pathogen powdery mildew (Erysiphe necator syn. Uncinula necator) and the oomycete pathogen downy mildew (Plasmopara viticola). Currently, grapegrowers rely heavily on the use of agrochemicals to minimize the potentially devastating impact of these pathogens on grape yield and quality. The wild North American grapevine species Muscadinia rotundifolia was recognized as early as 1889 to be resistant to both powdery and downy mildew. We have now mapped resistance to these two mildew pathogens in M. rotundifolia to a single locus on chromosome 12 that contains a family of seven TIR-NB-LRR genes. We further demonstrate that two highly homologous (86% amino acid identity) members of this gene family confer strong resistance to these unrelated pathogens following genetic transformation into susceptible Vitis vinifera winegrape cultivars. These two genes, designated resistance to Uncinula necator (MrRUN1) and resistance to Plasmopara viticola (MrRPV1) are the first resistance genes to be cloned from a grapevine species. Both MrRUN1 and MrRPV1 were found to confer resistance to multiple powdery and downy mildew isolates from France, North America and Australia; however, a single powdery mildew isolate collected from the south-eastern region of North America, to which M. rotundifolia is native, was capable of breaking MrRUN1-mediated resistance. Comparisons of gene organization and coding sequences between M. rotundifolia and the cultivated grapevine V. vinifera at the MrRUN1/MrRPV1 locus revealed a high level of synteny, suggesting that the TIR-NB-LRR genes at this locus share a common ancestor. PMID:24033846

  1. Construction of a reference linkage map of Vitis amurensis and genetic mapping of Rpv8, a locus conferring resistance to grapevine downy mildew.

    Science.gov (United States)

    Blasi, Paule; Blanc, Sophie; Wiedemann-Merdinoglu, Sabine; Prado, Emilce; Rühl, Ernst H; Mestre, Pere; Merdinoglu, Didier

    2011-06-01

    Downy mildew, caused by the oomycete Plasmopara viticola, is one of the major threats to grapevine. All traditional cultivars of grapevine (Vitis vinifera) are susceptible to downy mildew, the control of which requires regular application of fungicides. In contrast, many sources of resistance to P. viticola have been described in the Vitis wild species, among which is V. amurensis Rupr. (Vitaceae), a species originating from East Asia. A genetic linkage map of V. amurensis, based on 122 simple sequence repeat and 6 resistance gene analogue markers, was established using S1 progeny. This map covers 975 cM on 19 linkage groups, which represent 82% of the physical coverage of the V. vinifera reference genetic map. To measure the general level of resistance, the sporulation of P. viticola and the necrosis produced in response to infection, five quantitative and semi-quantitative parameters were scored 6 days post-inoculation on the S1 progeny. A quantitative trait locus (QTL) analysis allowed us to identify on linkage group 14 a major QTL controlling the resistance to downy mildew found in V. amurensis, which explained up to 86.3% of the total phenotypic variance. This QTL was named 'Resistance to Plasmopara viticola 8' (Rpv8). PMID:21404060

  2. Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression.

    LENUS (Irish Health Repository)

    Sen-Chowdhry, Srijita

    2007-04-03

    According to clinical-pathological correlation studies, the natural history of arrhythmogenic right ventricular dysplasia\\/cardiomyopathy is purported to progress from localized to global right ventricular dysfunction, followed by left ventricular (LV) involvement and biventricular pump failure. The inevitable focus on sudden death victims and transplant recipients may, however, have created a skewed perspective of a genetic disease. We hypothesized that unbiased representation of the spectrum of disease expression in arrhythmogenic right ventricular dysplasia\\/cardiomyopathy would require in vivo assessment of families in a genetically heterogeneous population.

  3. DYT1和DYT5的临床和遗传特征%Clinical and genetic features of DYT1 and DYT5

    Institute of Scientific and Technical Information of China (English)

    王小竹; Nanbert ZHONG

    2006-01-01

    Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13 subtypes. We mainly discussed two subtypes, DYT1 and DYT5, in this review. Early-onset primary dystonia is caused by the mutation of DYT1 gene, which leads to TORSINA abnormal. GTP cyclohydrolase 1 (GTPCH1)-deficient DRD(DYT5) is caused by the mutations of GCH1 gene. By genetic testing, we can confirm clinical diagnosis of each subtype and develop prenatal diagnosis for it.

  4. Clinical and genetic features of International Collaborative Group-hereditary nonpolyposis colorectal cancer families and suspected hereditary nonpolyposis colorectal cancer families

    Institute of Scientific and Technical Information of China (English)

    袁瑛; 叶俊; 郑树

    2004-01-01

    Background Hereditary nonpolyposis colorectal cancer (HNPPC) is one of the most common genetic syndrome related with mutation of human mismatch repair genes. This study was to evaluate the clinical significance of suspected hereditary nonpolyposis colorectal cancer (sHNPCC) criteria I and the clinical and genetic features of International Collaborative Group-HNPCC (ICG-HNPCC) and sHNPCC families.Methods Twenty-nine ICG-HNPCC families fulfilling the Amsterdam criteria and 34 sHNPCC families fulfilling the sHNPCC criteria I were collected. PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of the hMLH1 and hMSH2 genes in these families.Results The ICG group had more colorectal cancer (CRC) patients per family than did the suspected group (P0.05), mutation type, and mutation distribution. Comparison of the families with and without mutation showed no significant difference in CRC patients per family, Lynch classification, and tumor spectrum.Conclusions ICG-HNPCC and sHNPCC families that have similar clinical manifestations and genetic basis indicate a similar nature for cancer development. The application of sHNPCC criteria I will facilitate clinical diagnosis and treatment of small families.

  5. Conference Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    Computational fluid dynamics (CFD) is rapidly becoming a useful tool for simulating a variety of fluid flows. The 6. annual meeting of the Society in Quebec City discussed a wide variety of topics, organized into 15 sessions. Session titles included aerodynamics, shocks and detonations, geophysical and environmental flows, unsteady flows, multiphase flows, turbulence, natural convection, industrial applications, numerical techniques and simulations, heat and mass transfer, and moving boundary /interface problems. The use of CFD for mathematical modeling was demonstrated at this conference which included addresses by four guest speakers, 85 presentations, and 10 exhibits. refs., tabs., figs.

  6. Conference summaries

    International Nuclear Information System (INIS)

    The 113 papers presented at this conference covered the areas of 1) fuel design, development and production; 2) nuclear plant safety; 3) nuclear instrumentation; 4) public and regulatory matters; 5) developments and opportunities in fusion; 6) fuel behaviour under normal operating conditions; 7) nuclear plant design and operations; 8) materials science and technology; 9) nuclear power issues; 10) fusion technology; 11) fuel behaviour under accident conditions; 12) large scale fuel channel replacement programs; 13) thermalhydraulics experimental studies; 14) reactor physics and analysis; 15) applications of accelerators; 16) fission product release and severe fuel damage under accident conditions; 17) thermalhydraulics modeling and assessments; 18) waste management and the environment; and 20) new reactor concepts

  7. Functional analysis of differences in transcriptional activity conferred by genetic variants in the 5' flanking region of the IL12RB2 gene.

    Science.gov (United States)

    Kato-Kogoe, Nahoko; Ohyama, Hideki; Okano, Soichiro; Yamanegi, Koji; Yamada, Naoko; Hata, Masaki; Nishiura, Hiroshi; Abiko, Yoshimitsu; Terada, Nobuyuki; Nakasho, Keiji

    2016-01-01

    Interleukin 12 receptor β chain (IL12RB2) is a crucial regulatory factor involved in cell-mediated immune responses, and genetic variants of the gene encoding IL12RB2 are associated with susceptibility to various immune-related diseases. We previously demonstrated that haplotypes with single nucleotide polymorphisms (SNPs) in the 5' flanking region of IL12RB2, including -1035A>G (rs3762315) and -1023A>G (rs3762316), affect the expression of IL12RB2, thereby altering susceptibility to leprosy and periodontal diseases. In the present study, we identified transcription factors associated with the haplotype-specific transcriptional activity of IL12RB2 in T cells and NK cells. The -1023G polymorphism was found to create a consensus binding site for the transcription factor activating protein (AP)-1, and enzyme-linked immunosorbent assay (ELISA)-based binding assays showed that these SNPs enhanced AP-1 binding to this region. In reporter assays, suppression of JunB expression using siRNA eliminated differences in the -1035G/-1023G and -1035A/-1023A regions containing IL12RB2 promoter activity in Jurkat T cells and NK3.3 cells. These results suggested that the -1035/-1023 polymorphisms created differential binding affinities for JunB that could lead to differential IL12RB2 expression. Moreover, the -1035G and -1035A alleles formed binding sites for GATA-3 and myocyte enhancer factor-2 (MEF-2), respectively. Our data indicated that in addition to JunB, the SNP at -1035/-1023 influenced GATA-3 and MEF-2 binding affinity, potentially altering IL12RB2 transcriptional activity. These findings confirm the effects of rs3762315 and rs3762316 on IL12RB2 transcription. These genetic variants may alter cellular activation of T cells and NK cells and modify cell-mediated immune responses. PMID:26552659

  8. EGC Conferences

    CERN Document Server

    Ritschard, Gilbert; Pinaud, Bruno; Venturini, Gilles; Zighed, Djamel; Advances in Knowledge Discovery and Management

    This book is a collection of representative and novel works done in Data Mining, Knowledge Discovery, Clustering and Classification that were originally presented in French at the EGC'2012 Conference held in Bordeaux, France, on January 2012. This conference was the 12th edition of this event, which takes place each year and which is now successful and well-known in the French-speaking community. This community was structured in 2003 by the foundation of the French-speaking EGC society (EGC in French stands for ``Extraction et Gestion des Connaissances'' and means ``Knowledge Discovery and Management'', or KDM). This book is intended to be read by all researchers interested in these fields, including PhD or MSc students, and researchers from public or private laboratories. It concerns both theoretical and practical aspects of KDM. The book is structured in two parts called ``Knowledge Discovery and Data Mining'' and ``Classification and Feature Extraction or Selection''. The first part (6 chapters) deals with...

  9. Munich conference

    International Nuclear Information System (INIS)

    'The Standard Model has survived impact for another year', declared Don Perkins of Oxford, summarizing the 24th International Conference on High Energy Physics held in Munich from 4-10 August. 'But is this a triumph or a frustration for physics?' he added. The twin pillars of the Standard Model, the electroweak unification of electromagnetism and the weak nuclear force, and the field theory (quantum chromodynamics) of the quark-gluon interactions responsible for the strong nuclear force, have not trembled since the electroweak unification went to the textbooks in 1983, but from time to time small cracks have appeared which might have gone on to shake the theory severely, if not undermine it. Major conference summarizers have got used to singing the praises of the Standard Model, but this year at Munich even detailed examination failed to reveal any serious cracks, while looking deeper into physics even some anomalous results hinting at gaps in understanding have either gone away or have diminished credibility

  10. NATO Conference

    CERN Document Server

    Lynn, W

    1975-01-01

    The contents of this volume involve selection, emendation and up-dating of papers presented at the NATO Conference "Mathe­ matical Analysis of Decision problems in Ecology" in Istanbul, Turkey, July 9-13, 1973. It was sponsored by the System Sciences Division of NATO directed by Dr. B. Bayraktar with local arrange­ ments administered by Dr. Ilhami Karayalcin, professor of the Department of Industrial Engineering at the Technical University of Istanbul. It was organized by A. Charnes, University professor across the University of Texas System, and Walter R.Lynn, Di­ rector of the School of Civil and Environmental Engineering at Cornell Unjversity. The objective of the conference was to bring together a group of leading researchers from the major sciences involved in eco­ logical problems and to present the current state of progress in research of a mathematical nature which might assist in the solu­ tion of these problems. Although their presentations are not herein recorded, the key­ note address of Dr....

  11. Profile of patients with genitourinary anomalies treated in a clinical genetics service in the Brazilian unified health system

    Science.gov (United States)

    Gazzaneo, Ilanna Fragoso Peixoto; de Queiroz, Camila Maia Costa; Goes, Larissa Clara Vieira; Lessa, Victor José Correia; de Omena, Reinaldo Luna; do Nascimento, Diogo Lucas Lima; Petroli, Reginaldo José; Zanotti, Susane Vasconcelos; Monlleó, Isabella Lopes

    2016-01-01

    Abstract Objective: To describe the profile of patients with genitourinary abnormalities treated at a tertiary hospital genetics service. Methods: Cross-sectional study of 1068 medical records of patients treated between April/2008 and August/2014. A total of 115 cases suggestive of genitourinary anomalies were selected, regardless of age. A standardized clinical protocol was used, as well as karyotype, hormone levels and genitourinary ultrasound for basic evaluation. Laparoscopy, gonadal biopsy and molecular studies were performed in specific cases. Patients with genitourinary malformations were classified as genitourinary anomalies (GUA), whereas the others, as Disorders of Sex Differentiation (DSD). Chi-square, Fisher and Kruskal–Wallis tests were used for statistical analysis and comparison between groups. Results: 80 subjects met the inclusion criteria, 91% with DSD and 9% with isolated/syndromic GUA. The age was younger in the GUA group (p<0.02), but these groups did not differ regarding external and internal genitalia, as well as karyotype. Karyotype 46,XY was verified in 55% and chromosomal aberrations in 17.5% of cases. Ambiguous genitalia occurred in 45%, predominantly in 46,XX patients (p<0.006). Disorders of Gonadal Differentiation accounted for 25% and congenital adrenal hyperplasia, for 17.5% of the sample. Consanguinity occurred in 16%, recurrence in 12%, lack of birth certificate in 20% and interrupted follow-up in 31% of cases. Conclusions: Patients with DSD predominated. Ambiguous genitalia and abnormal sexual differentiation were more frequent among infants and prepubertal individuals. Congenital adrenal hyperplasia was the most prevalent nosology. Younger patients were more common in the GUA group. Abandonment and lower frequency of birth certificate occurred in patients with ambiguous or malformed genitalia. These characteristics corroborate the literature and show the biopsychosocial impact of genitourinary anomalies. PMID:26522823

  12. Profile of patients with genitourinary anomalies treated in a clinical genetics service in the Brazilian unified health system

    Directory of Open Access Journals (Sweden)

    Ilanna Fragoso Peixoto Gazzaneo

    2016-03-01

    Full Text Available Abstract Objective: To describe the profile of patients with genitourinary abnormalities treated at a tertiary hospital genetics service. Methods: Cross-sectional study of 1068 medical records of patients treated between April/2008 and August/2014. A total of 115 cases suggestive of genitourinary anomalies were selected, regardless of age. A standardized clinical protocol was used, as well as karyotype, hormone levels and genitourinary ultrasound for basic evaluation. Laparoscopy, gonadal biopsy and molecular studies were performed in specific cases. Patients with genitourinary malformations were classified as genitourinary anomalies (GUA, whereas the others, as Disorders of Sex Differentiation (DSD. Chi-square, Fisher and Kruskal–Wallis tests were used for statistical analysis and comparison between groups. Results: 80 subjects met the inclusion criteria, 91% with DSD and 9% with isolated/syndromic GUA. The age was younger in the GUA group (p<0.02, but these groups did not differ regarding external and internal genitalia, as well as karyotype. Karyotype 46,XY was verified in 55% and chromosomal aberrations in 17.5% of cases. Ambiguous genitalia occurred in 45%, predominantly in 46,XX patients (p<0.006. Disorders of Gonadal Differentiation accounted for 25% and congenital adrenal hyperplasia, for 17.5% of the sample. Consanguinity occurred in 16%, recurrence in 12%, lack of birth certificate in 20% and interrupted follow-up in 31% of cases. Conclusions: Patients with DSD predominated. Ambiguous genitalia and abnormal sexual differentiation were more frequent among infants and prepubertal individuals. Congenital adrenal hyperplasia was the most prevalent nosology. Younger patients were more common in the GUA group. Abandonment and lower frequency of birth certificate occurred in patients with ambiguous or malformed genitalia. These characteristics corroborate the literature and show the biopsychosocial impact of genitourinary anomalies.

  13. 临床医学专业学位试点工作阶段的问题和对策%Discussion of the questions and the related solutions in the experimental stage of conferring the clinical medical degrees

    Institute of Scientific and Technical Information of China (English)

    陈地龙; 黄萌; 秦跃文; 徐永柱

    2000-01-01

    试行临床医学专业学位是我国医学学位与研究生教育改革的一项重大举措。笔者根据本校试点工作中出现的问题,提出了临床医学专业学位试点工作的若干对策。%Carrying out the conferring of the clinical medicial professional degrees is one of the important measures in the reform of the medical degree granting and postgraduate education in our country. We now put forward the following suggestions about the experimental granting of the professional degrees of clinical medicine in our school on the basis of our past experience in this respect.

  14. Genetic variation in the Cytb gene of human cerebral Taenia solium cysticerci recovered from clinically and radiologically heterogeneous patients with neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Hector Palafox-Fonseca

    2013-11-01

    Full Text Available Neurocysticercosis (NC is a clinically and radiologically heterogeneous parasitic disease caused by the establishment of larval Taenia solium in the human central nervous system. Host and/or parasite variations may be related to this observed heterogeneity. Genetic differences between pig and human-derived T. solium cysticerci have been reported previously. In this study, 28 cysticerci were surgically removed from 12 human NC patients, the mitochondrial gene that encodes cytochrome b was amplified from the cysticerci and genetic variations that may be related to NC heterogeneity were characterised. Nine different haplotypes (Ht, which were clustered in four haplogroups (Hg, were identified. Hg 3 and 4 exhibited a tendency to associate with age and gender, respectively. However, no significant associations were found between NC heterogeneity and the different T. solium cysticerci Ht or Hg. Parasite variants obtained from patients with similar NC clinical or radiological features were genetically closer than those found in groups of patients with a different NC profile when using the Mantel test. Overall, this study establishes the presence of genetic differences in the Cytb gene of T. solium isolated from human cysticerci and suggests that parasite variation could contribute to NC heterogeneity.

  15. A 20 year history of clinical and genetic study of thyroid autoimmunity in a Tunisian multigenerational family: Evidence for gene interaction☆

    Science.gov (United States)

    Bougacha-Elleuch, Noura; Charfi, Nadia; Kharrat, Najla; Ayadi, Fatma; Maalej, Abdellatif; Chabchoub, Ghazi; Rebai, Ahmed; Kammoun-Krichen, Maha; Belguith-Maalej, Salima; Abid, Mohamed; Mnif, Mouna; Ayadi, Hammadi

    2013-01-01

    Autoimmune thyroid diseases (AITD), which include Hashimoto thyroiditis (HT), Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized by their clinical and genetic heterogeneity. In this study, we have carried on a global approach gathering 20 year genetic and clinical data on a Tunisian multigenerational family (Akr). Our purpose was search for a combined genotype involved in AITD susceptibility using 33 gene polymorphisms. The Akr pedigree is composed of more than 400 members distributed on 10 generations. Clinical follow-up was performed by appreciation of the thyroid gland and measurement of both thyroid hormone and auto antibody levels. We used FBAT software to test for association between gene polymorphisms and AITDs. Clinical follow-up has showed that the number of AITD patients has increased from 25 to 78 subjects subdivided on 51 cases of GD, 22 PIM and 5 HT. Concerning genetic analysis, our study has revealed new gene association when compared with our previous analysis (considering single genes). Thus, PTPN22, TG and VDR gene polymorphisms have became associated with p-values ranging from 4.6  10− 2 to 4  10− 3 when considered with other genes on the same chromosome; giving evidence for gene interaction. The most significant association was found with the MHC region (p = 7.15 10− 4). Moreover, and among gene polymorphisms explored, our analysis has identified some of them as AITD biomarkers. Indeed, PDS gene polymorphisms were associated with either exophthalmia or goiter (p-values from 10− 2 to 10− 3). In conclusion, our study gives evidence for gene interaction in AITD development confirming genetic complexity of these diseases. PMID:25606390

  16. A 20 year history of clinical and genetic study of thyroid autoimmunity in a Tunisian multigenerational family: Evidence for gene interaction

    Directory of Open Access Journals (Sweden)

    Noura Bougacha-Elleuch

    2014-12-01

    Full Text Available Autoimmune thyroid diseases (AITD, which include Hashimoto thyroiditis (HT, Graves' disease (GD and primary idiopathic myxoedema (PIM, are recognized by their clinical and genetic heterogeneity. In this study, we have carried on a global approach gathering 20 year genetic and clinical data on a Tunisian multigenerational family (Akr. Our purpose was search for a combined genotype involved in AITD susceptibility using 33 gene polymorphisms. The Akr pedigree is composed of more than 400 members distributed on 10 generations. Clinical follow-up was performed by appreciation of the thyroid gland and measurement of both thyroid hormone and auto antibody levels. We used FBAT software to test for association between gene polymorphisms and AITDs. Clinical follow-up has showed that the number of AITD patients has increased from 25 to 78 subjects subdivided on 51 cases of GD, 22 PIM and 5 HT. Concerning genetic analysis, our study has revealed new gene association when compared with our previous analysis (considering single genes. Thus, PTPN22, TG and VDR gene polymorphisms have became associated with p-values ranging from 4.6   10−2 to 4   10−3 when considered with other genes on the same chromosome; giving evidence for gene interaction. The most significant association was found with the MHC region (p = 7.15 10−4. Moreover, and among gene polymorphisms explored, our analysis has identified some of them as AITD biomarkers. Indeed, PDS gene polymorphisms were associated with either exophthalmia or goiter (p-values from 10−2 to 10−3. In conclusion, our study gives evidence for gene interaction in AITD development confirming genetic complexity of these diseases.

  17. BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk

    DEFF Research Database (Denmark)

    Spurdle, Amanda B; Whiley, Phillip J; Thompson, Bryony;

    2012-01-01

    Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional...... transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer....

  18. THE EFFECTS OF CLINICAL PATHOLOGICAL CONFERENCE IN ROTATION TRAINING OF GENERAL PRACTITIONER IN NEPHROLOGY DEPARTMENT%临床病理讨论会在全科医生肾脏科转岗培训中的效果

    Institute of Scientific and Technical Information of China (English)

    刘海军

    2014-01-01

    Objective To explore the effects of clinical pathological conference in rotation training of gen-eral practitioner in nephrology department to promote the realization of general practice training goal . Methods From August ,2009 to December ,2012 ,65 general practitioners from Linyi City People’s Hospi-tal who have accepted standardized training for general practitioners were enrolled .They actively participa-ted in clinical pathological conference in nephrology department one time a week .theory ,skills and medi-cal record writing At the end of rotation training ,the training effects were assessed in knowledge ,skills and writing medical history .Questionnaires were used to survey general practitioners’ evaluation of the mode of clinical pathological conference .Results The knowledge ,skills and medical record writing were all up to standard ,and the excellence rates were is 60 (92 .31% ) ,62 (95 .38% ) and 58/(89 .23% ) respective-ly .The survey results showed that the general practitioners gave high evaluation to the mode of clinical pathological conference ,and the mode can mobilize the initiative and enthusiasm and can improve the theo-retical and practical ability in the diagnosis and treatment of kidney diseases in community .Conclusion Clin-ical pathological conference has positive effect on general practitioners’ knowledge and practice skills and can help to ensure the realization of general medical teaching goal .%目的:探索临床病理讨论会模式在全科医生肾脏科轮岗培训中的应用效果,促进全科医学培养目标的实现。方法选择2009年8月~2012年12月在临沂市人民医院肾脏科接受规范化培训的全科医生65人,在肾脏科轮岗期间,每周进行1次临床病理讨论会,轮岗结束时考核理论、技能、病历书写等效果,问卷调查全科医生对临床-病理讨论会模式的评价。结果出科时理论、技能考核及病历书写成绩均合格

  19. Contribution of Genetic Background and Clinical Risk Factors to Low-Trauma Fractures in Human Immunodeficiency Virus (HIV)-Positive Persons: The Swiss HIV Cohort Study

    Science.gov (United States)

    Junier, Thomas; Rotger, Margalida; Biver, Emmanuel; Ledergerber, Bruno; Barceló, Catalina; Bartha, Istvan; Kovari, Helen; Schmid, Patrick; Fux, Christoph; Bernasconi, Enos; Brun del Re, Claudia; Weber, Rainer; Fellay, Jacques; Tarr, Philip E.

    2016-01-01

    Background. The impact of human genetic background on low-trauma fracture (LTF) risk has not been evaluated in the context of human immunodeficiency virus (HIV) and clinical LTF risk factors. Methods. In the general population, 6 common single-nucleotide polymorphisms (SNPs) associate with LTF through genome-wide association study. Using genome-wide SNP arrays and imputation, we genotyped these SNPs in HIV-positive, white Swiss HIV Cohort Study participants. We included 103 individuals with a first, physician-validated LTF and 206 controls matched on gender, whose duration of observation and whose antiretroviral therapy start dates were similar using incidence density sampling. Analyses of nongenetic LTF risk factors were based on 158 cases and 788 controls. Results. A genetic risk score built from the 6 LTF-associated SNPs did not associate with LTF risk, in both models including and not including parental hip fracture history. The contribution of clinical LTF risk factors was limited in our dataset. Conclusions. Genetic LTF markers with a modest effect size in the general population do not improve fracture prediction in persons with HIV, in whom clinical LTF risk factors are prevalent in both cases and controls.

  20. MUSME Conference

    CERN Document Server

    Martinez, Eusebio

    2015-01-01

    This volume contains the Proceedings of MUSME 2014, held at Huatulco in Oaxaca, Mexico, October 2014. Topics include analysis and synthesis of mechanisms; dynamics of multibody systems; design algorithms for mechatronic systems; simulation procedures and results; prototypes and their performance; robots and micromachines; experimental validations; theory of mechatronic simulation; mechatronic systems; and control of mechatronic systems. The MUSME symposium on Multibody Systems and Mechatronics was held under the auspices of IFToMM, the International Federation for Promotion of Mechanism and Machine Science, and FeIbIM, the Iberoamerican Federation of Mechanical Engineering. Since the first symposium in 2002, MUSME events have been characterised by the way they stimulate the integration between the various mechatronics and multibody systems dynamics disciplines, present a forum for facilitating contacts among researchers and students mainly in South American countries, and serve as a joint conference for the ...

  1. Conference Proceedings

    International Nuclear Information System (INIS)

    This volume contains the unedited proceedings of the Second Annual Conference on Managing Electricity Price Volatility. There were a total of eleven papers presented, dealing with a variety of issues affecting price volatility. Subjects treated included: new power generation development in Alberta; an analysis of electricity supply and demand to predict future price volatility; the effect of government intervention in the Alberta electricity market; risk management in volatile energy markets; an analysis of Alberta's capacity to supply its own internal electric power needs; the impact of increased electricity import and export capacity on price fluctuation in Alberta; improving market liquidity in Alberta; using weather derivatives to offset price risk; the impact of natural gas prices on electricity price volatility; capitalizing on advancements in online trading; and strategies for businesses to keep operating through times of price volatility. In most cases only overhead viewgraphs are available

  2. The Ninth International Conference on Machine Learning

    OpenAIRE

    Segre, Maria

    1993-01-01

    The Ninth International Conference on Machine Learning was held in Aberdeen, Scotland, from 1-3 July 1992, with 198 participants in attendance. The conference covered a broad range of topics drawn from the general area of machine learning, including concept-learning algorithms, clustering, speedup learning, formal analysis of learning systems, neural networks, genetic algorithms, and applications of machine learning. This article briefly touches on six selected talks that were of exceptional ...

  3. Characterization of Klebsiella sp. strain 10982, a colonizer of humans that contains novel antibiotic resistance alleles and exhibits genetic similarities to plant and clinical Klebsiella isolates.

    Science.gov (United States)

    Hazen, Tracy H; Zhao, LiCheng; Sahl, Jason W; Robinson, Gwen; Harris, Anthony D; Rasko, David A; Johnson, J Kristie

    2014-01-01

    A unique Klebsiella species strain, 10982, was cultured from a perianal swab specimen obtained from a patient in the University of Maryland Medical Center intensive care unit. Klebsiella sp. 10982 possesses a large IncA/C multidrug resistance plasmid encoding a novel FOX AmpC β-lactamase designated FOX-10. A novel variant of the LEN β-lactamase was also identified. Genome sequencing and bioinformatic analysis demonstrated that this isolate contains genes associated with nitrogen fixation, allantoin metabolism, and citrate fermentation. These three gene regions are typically present in either Klebsiella pneumoniae clinical isolates or Klebsiella nitrogen-fixing endophytes but usually not in the same organism. Phylogenomic analysis of Klebsiella sp. 10982 and sequenced Klebsiella genomes demonstrated that Klebsiella sp. 10982 is present on a branch that is located intermediate between the genomes of nitrogen-fixing endophytes and K. pneumoniae clinical isolates. Metabolic features identified in the genome of Klebsiella sp. 10982 distinguish this isolate from other Klebsiella clinical isolates. These features include the nitrogen fixation (nif) gene cluster, which is typically present in endophytic Klebsiella isolates and is absent from Klebsiella clinical isolates. Additionally, the Klebsiella sp. 10982 genome contains genes associated with allantoin metabolism, which have been detected primarily in K. pneumoniae isolates from liver abscesses. Comparative genomic analysis of Klebsiella sp. 10982 demonstrated that this organism has acquired genes conferring new metabolic strategies and novel antibiotic resistance alleles, both of which may enhance its ability to colonize the human body. PMID:24395222

  4. Conference summaries

    International Nuclear Information System (INIS)

    The summaries were derived from presentations, interviews and discussions at the conference. The summaries are given at two levels, overall for the conference and for specific sessions as follows: 1) Overall Conference: 'A Sound Scientific Basis for Serious Decisions; 2) Sessions on EC Policy and Socio-Political Issues: 'Promoting Safety and Protecting Society'; 3) Session on P and T: 'Partitioning and Transmutation: A Technical Fix or Technical Training?'; 4) Sessions on Geological Disposal and Research Networking: 'No Technical Barriers to Geological Disposal'. First an overall summary of Euradwaste '04 is presented. Significant progress was made on the technical and scientific basis for geological disposal of radioactive waste during the European Commission's Fifth EURATOM Framework Programme for Research (FP5). Deep geological disposal is technically feasible now and can demonstrate the guarantees of long-term isolation and protection of the public. In parallel, socio-political studies have produced methodologies for constructive dialogue with potential host communities that reflect the honesty and openness expected by a democratic society. A harmonized legislative framework for nuclear safety and waste disposal across the enlarged European Union is currently being discussed. Disposal in deep (> 300 metre) geological repositories, the favoured strategy in Europe for long-lived high-level radioactive waste, is now possible. The Sessions on EC Policy and Socio-Political Issues are summarized as follows. The opening day of Euradwaste '04 focused on European Commission policy, including the proposed Directives on disposal of radioactive waste and nuclear safety and socio-political aspects including governance and decision making, public perception/acceptance of waste disposal and its sustainability. A decision on the proposed package will now be made after Union enlargement. Public agreement on the siting of disposal facilities is controversial and more important

  5. Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia

    NARCIS (Netherlands)

    Schelhaas, H J; Ippel, P F; Hageman, G; Sinke, R J; van der Laan, E N; Beemer, F A

    2001-01-01

    The autosomal dominant cerebellar ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders characterised by progressive cerebellar dysfunction in combination with a variety of other associative features. Since 1993 ADCAs have been increasingly characterised in terms of their genetic

  6. 13th International Conference on Chlamydomonas

    Energy Technology Data Exchange (ETDEWEB)

    Silflow, Carolyn D. [University of Minnesota

    2014-03-11

    The 13th International Conference on Chlamydomonas (EMBO Workshop on the Cell and Molecular Biology of Chlamydomonas) was held May 27 to June 1, 2008 in Hyeres, France. The conference was the biennial meeting for all researchers studying the green algal systems Chlamydomonas and Volvox. The conference brought together approximately 200 investigators from around the world (North America, Asia, Europe and Australia) representing different fields and disciplines (cell biology, genetics, biochemistry, biophysics, plant physiology, genomics). It provided an opportunity for investigators from different countries to share methodologies and to discuss recent results with a focus on the Chlamydomonas experimental system.

  7. PHYSICS FOR HEALTH: CONFERENCE HIGHLIGHTS

    CERN Multimedia

    2016-01-01

    Highlights of ICTR-PHE 2016 - International Conference on Translational Research in Radio-Oncology and Physics for Health -, co organized by CERN, aims at developing new strategies to better diagnose and treat cancer, by uniting biology and physics with clinics. Through the various sessions and symposia, the scientific programme offers the delegates the opportunity to discuss, in a friendly atmosphere, the latest progress in physics breakthroughs for health applications. The third edition of this conference took place at CICG (Centre International de Conférence Genève) from 15 to 19 Feb 2016.

  8. Genetic Diversity of Mycobacterium avium Isolates Recovered from Clinical Samples and from the Environment: Molecular Characterization for Diagnostic Purposes▿

    OpenAIRE

    Álvarez, Julio; García, Ignacio Gómez; Aranaz, Alicia; Bezos, Javier; Romero, Beatriz; de Juan, Lucía; Mateos, Ana; Gómez-Mampaso, Enrique; Domínguez, Lucas

    2008-01-01

    Isolation of Mycobacterium avium complex (MAC) organisms from clinical samples may occur in patients without clinical disease, making the interpretation of results difficult. The clinical relevance of MAC isolates from different types of clinical samples (n = 47) from 39 patients in different sections of a hospital was assessed by comparison with environmental isolates (n = 17) from the hospital. Various methods for identification and typing (commercial probes, phenotypic characteristics, PCR...

  9. First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar

    DEFF Research Database (Denmark)

    Dubois, A. E. J.; Pagliarani, G.; Brouwer, R. M.;

    2015-01-01

    BACKGROUND: Genetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals. METHODS: We performed oral food challenges in 21 apple-allergic individuals with Elstar apples...... which had undergone gene silencing of the major allergen of apple, Mal d 1, by RNA interference. Downregulation of Mal d 1 gene expression in the apples was verified by qRT-PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild-type Elstar using a visual...... analogue scale (VAS). RESULTS: Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 gene mRNA levels which were extensively downregulated, that is only 0.1-16.4% (e-DR1) and 0.2-9.9% (e-DR2) of those of the wild-type Elstar, respectively. Challenges with...

  10. International Conference on Health Informatics

    CERN Document Server

    2014-01-01

    This volume presents the proceedings of the International Conference on Health Informatics (ICHI). The conference was a new special topic conference initiative by the International Federation of Medical and Biological Engineering (IFMBE), held in Vilamoura, Portugal on 7-9 November, 2013. The main theme of the ICHI2013 was “Integrating Information and Communication Technologies with Biomedicine for Global Health”. The proceedings offer a unique forum to examine enabling technologies of sensors, devices and systems that optimize the acquisition, transmission, processing, storage, retrieval of biomedical and health information as well as to report novel clinical applications of health information systems and the deployment of m-Health, e-Health, u-Health, p-Health and Telemedicine.

  11. AMIA Conference 2006 “Partnerships in Innovation”: Intermountain Healthcare and GE Healthcare—Partnering to Build a World-Class Clinical Information System

    OpenAIRE

    2006-01-01

    Intermountain Healthcare, one of the leading integrated delivery networks in the country, has established a software development partnership with GE Healthcare’s Integrated IT Solutions business to create the next-generation clinical information system. The 10-year development deal focuses primarily on electronic medical records, with additional work being done on decision support, data warehousing, and hospital and clinic automation—all with the goal of improving patient care. Headquartered ...

  12. Clinically relevant fluoroquinolone resistance due to constitutive overexpression of the PatAB ABC transporter in Streptococcus pneumoniae is conferred by disruption of a transcriptional attenuator

    OpenAIRE

    Baylay, Alison J.; Piddock, Laura J. V.

    2014-01-01

    Objectives Constitutive overexpression of patAB has been observed in several unrelated fluoroquinolone-resistant laboratory mutants and clinical isolates; therefore, we sought to identify the cause of this overexpression. Methods Constitutive patAB overexpression in two clinical isolates and a laboratory-selected mutant was investigated using a whole-genome transformation approach. To determine the effect of the detected terminator mutations, the WT and mutated patA leader sequences were clon...

  13. Conference Papers

    International Nuclear Information System (INIS)

    A total of 18 papers were presented at the 2003 Annual Executive Conference of the Canadian Gas Association held at St. Andrews, NB, from June 25th to June 28th. Titles of the presentations were as follows: (1) 'Positioning natural gas in a transforming world' by Pierre Marcel Desjardins; (2) 'Positioning natural gas in a transforming world' by Jean-Paul Theoret; (3) 'Perceptions of natural gas' by Noel Sampson; (4) 'Energy efficiency as an opportunity for the natural gas industry' by Peter Love; (5) 'Natural gas R and D - NRCan perspective' by Graham R. Campbell; (6) 'Impact of earned media on corporate perceptions in the gas industry' by Michael Coates; (7) 'Moving forward with an initiative for natural gas technology innovation' by Emmanuel Morin; (8) 'Natural gas R and D - No more dodging the issue' by Chuck Szmurlo; (9) 'Meeting the technology needs of the gas industry and the gas consumer' by Stanley S. Borys; (10) 'Market signals' by John Wellard; (11) 'Future sources of Canadian natural gas' by Rick Hyndman; (12) 'The state of supply: Northeast U.S. perspective' by Tom Kiley; (13) 'AGA's priorities and perspectives' by Dick Reiten; (14) 'Global energy issues: Recent development in policy and business' by Gerald Doucet; (15) 'Keeping the distribution cart behind the horse: Why finding more offshore gas is much more important than completing the natural gas grid, including for New Brunswick' by Brian Lee Crowley; (16) 'Environmental opportunities and challenges for the gas industry' by Manfred Klein; (17) 'The potential for natural gas demand destruction' by Timothy Partridge; and (18) 'Pushing the envelope on gas supply' by Roland R. George. In most instances only speaking notes and view graphs are available

  14. PBL教学法和CPC教学法在病理学实验课中的应用%Application of Problem-based Learning and Clinical Pathology Conference in Pathology Classroom Practice

    Institute of Scientific and Technical Information of China (English)

    李娟; 胡晓松; 刘馨莲; 孙静; 李淑蓉

    2007-01-01

    病理学是一门联系基础医学和临床医学的桥梁课程,实验课是病理学教学中的重要环节,传统教学法不能充分调动学生学习的积极性,已难适应本科教学的要求.为此,作者在教学中开始尝试以问题为基础的学习法(problem-based learning,PBL)和临床病理讨论(clinical pathology conference,CPC),提高教学效果,培养学生的创造性和积极思考能力.

  15. Strategies to work with HLA data in human populations for histocompatibility, clinical transplantation, epidemiology and population genetics

    DEFF Research Database (Denmark)

    Sanchez-Mazas, A; Vidan-Jeras, B; Nunes, J M;

    2012-01-01

    outcome is the provision of population genetic characterizations and comparisons in a standard way by all interested laboratories. This article reports the recommendations of four working groups (WG1-4) of the HLA-NET network at the mid-term of its activities. WG1 (Population definitions and sampling......HLA-NET (a European COST Action) aims at networking researchers working in bone marrow transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human populations, with an expected strong impact on both public health...... and fundamental research. Such improvements involve finding consensual strategies to characterize human populations and samples and report HLA molecular typings and ambiguities; proposing user-friendly access to databases and computer tools and defining minimal requirements related to ethical aspects. The overall...

  16. Genetic relatedness of selected clinical Vibrio cholerae O139 isolates from the southern coastal area of China over a 20-year period.

    Science.gov (United States)

    Li, B S; Xiao, Y; Wang, D C; Tan, H L; Ke, B X; He, D M; Ke, C W; Zhang, Y H

    2016-09-01

    Vibrio cholerae O139 emerged as a causative agent of epidemic cholera in 1992 in India and Bangladesh, and was subsequently reported in China in 1993. The genetic relatedness and molecular characteristics of V. cholerae O139 in Guangdong Province, located in the southern coastal area of China, remains undetermined. In this study, we investigated 136 clinical V. cholerae O139 isolates from 1993 to 2013 in Guangdong. By conventional PCR, 123 (90·4%) isolates were positive for ctxB, ace and zot. Sequencing of the positive amplicons indicated 113 (91·7%) isolates possessed the El Tor allele of ctxB (genotype 3); seven carried the classical ctxB type (genotype 1) and three harboured a novel ctxB type (genotype 5). With respect to tcpA, 123 (90·4%) isolates were positive for the El Tor allele. In addition, pulsed-field gel electrophoresis (with NotI digestion) differentiated the isolates into clusters A and B. Cluster A contained seven of the non-toxigenic isolates from 1998 to 2000; another six non-toxigenic isolates (from 1998 and 2007) and all of the toxigenic isolates formed cluster B. Our results suggest that over a 20-year period, the predominant O139 clinical isolates have maintained a relatively tight clonal structure, although some genetic variance and shift has occurred. Our data highlight the persistence of toxigenic V. cholerae O139 in clinical settings in the southern coastal area of China. PMID:27305977

  17. Comparative analysis of genetic diversity and incidence of virulence factors and antibiotic resistance among enterococcal populations from raw fruit and vegetable foods, water and soil, and clinical samples.

    Science.gov (United States)

    Abriouel, Hikmate; Omar, Nabil Ben; Molinos, Antonio Cobo; López, Rosario Lucas; Grande, Maria José; Martínez-Viedma, Pilar; Ortega, Elena; Cañamero, Magdalena Martínez; Galvez, Antonio

    2008-03-31

    A comparative study was carried out among enterococci isolated from fruits and vegetable foods, water and soil, and clinical samples. Results indicate strong differences in the numbers of enterococcal species found in different environments as well as their abundance. While Enterococcus faecalis was clearly the predominant species in clinical samples, Enterococcus faecium predominated in vegetables, and it slightly outnumbered E. faecalis in water samples. Other species (Enterococcus hirae, Enterococcus mundtii, Enterococcus durans, Enterococcus gallinarum and Enterococcus casseliflavus) were found more frequently in vegetables, water, and specially in soil. Isolates from vegetable foods showed a lower incidence of antibiotic resistance compared to clinical isolates for most antimicrobials tested, especially erythromycin, tetracycline, chloramphenicol, ciprofloxacin, levofloxacin, gentamicin and streptomycin for E. faecalis, and quinupristin/dalfopristin, ampicillin, penicillin, ciprofloxacin, levofloxacin, rifampicin, choramphenicol, gentamicin and nitrofurantoin for E. faecium. E. faecium isolates from vegetable foods and water showed an average lower number of antibiotic resistance traits (2.95 and 3.09 traits for vegetable and water isolates, respectively) compared to clinical samples (7.5 traits). Multi-resistant strains were also frequent among clinical E. faecalis isolates (5.46 traits on average). None of E. faecalis or E. faecium isolates from vegetable foods, water and soil showed beta-haemolytic activity, while 25.64% of clinical E. faecalis did. A 51.28% of E. faecalis clinical isolates tested positive for the cylA, cylB, cylM set of genes, while some or all of these genes were missing in the rest of isolates. In clinical E. faecalis and E. faecium isolates, the genetic determinants for the enterococcal surface protein gene (esp), the collagen adhesin gene (ace) and the sex pheromone gene ccf (as well as cob in E. faecalis) showed a clearly higher

  18. A comparison of the genetic and clinical profile of men that respond and do not respond to the immediate antihypertensive effects of aerobic exercise

    Directory of Open Access Journals (Sweden)

    Linda S Pescatello

    2008-09-01

    Full Text Available Linda S Pescatello1, Bruce E Blanchard2, Gregory J Tsongalis3, Ann A O’Connell4, Heather Gordish-Dressman5, Carl M Maresh1, Paul D Thompson61Department of Kinesiology, University of Connecticut, Storrs, CT, USA; 2Department of Pathology; 3Department of Pathology, Dartmouth Medical School and Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA; 4School of Educational Policy and Leadership, Ohio State University, Columbus, OH, USA; 5Research Center for Genetic Medicine, Children’s National Medical Center, Washington, DC, USA; 6Division of Cardiology, Hartford Hospital, Hartford, CT, USAAbstract: We compared the genetic and clinical profile of men who lower and do not lower blood pressure (BP after acute aerobic exercise. Volunteers were 45 men (Mean ± SEM, 43.5 ± 1.5 yr with high BP (145.7 ± 1.5/85.7 ± 1.1 mmHg. They completed three experiments: nonexercise control and two cycle exercise sessions at 40% and 60% peak oxygen consumption, and were then instrumented to an ambulatory BP monitor. Logistic regression determined the genetic and clinical profile of men who lowered BP after exercise (responders [ExR n = 36]; and those who did not (nonresponders [ExNR n = 9]. ExR had higher C-reactive protein (CRP, high-density lipoprotein (HDL, the metabolic syndrome, family history of hypertension, more renin-angiotensin system (RAS common alleles, and α-adducin Trp460 and endothelial nitric oxide synthase (ENOS C786 risk alleles. ExNR had lower CRP and HDL, did not have the metabolic syndrome and a family history of hypertension, had more RAS risk alleles, and had the α-adducin Gly460Gly and ENOS T786T genotypes. This model had a sensitivity of 97.1%, specificity of 75.0%, and accounted for 46.3%–74.4% of the BP response. These results suggest genetic and clinical information may eventually be used to characterize people who do and do not respond to exercise as antihypertensive therapy.Keywords: blood pressure, genetics, hypertension

  19. Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations

    Science.gov (United States)

    Demirbilek, Huseyin; Arya, Ved Bhushan; Ozbek, Mehmet Nuri; Houghton, Jayne A L; Baran, Riza Taner; Akar, Melek; Tekes, Selahattin; Tuzun, Heybet; Mackay, Deborah J; Flanagan, Sarah E; Hattersley, Andrew T; Ellard, Sian; Hussain, Khalid

    2015-01-01

    Background Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. Design and methods NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. Results Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. Conclusions Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort. PMID:25755231

  20. Insertion- and Deletion-Associated Genetic Diversity of Mycobacterium tuberculosis Phospholipase C-Encoding Genes among 106 Clinical Isolates from Turkey

    OpenAIRE

    Talarico, Sarah; Durmaz, Riza; Yang, Zhenhua

    2005-01-01

    Bacterial phospholipase C has been reported to play a role in the pathogenesis of many bacteria. In order to gain a better understanding of the potential role of Mycobacterium tuberculosis phospholipase C in the pathogenesis of human tuberculosis, we investigated the genetic diversity of the four M. tuberculosis phospholipase C-encoding genes (plcA, plcB, plcC, and plcD) resulting from the IS6110 insertion and associated deletion, among 106 clinical isolates obtained from Turkey, by using PCR...

  1. Bordetella bronchiseptica Pneumonia in an Infant and Genetic Comparison of Clinical Isolates with Veterinary Kennel Cough Vaccines

    Science.gov (United States)

    An infant with recurrent episodes of respiratory failure was diagnosed with pertussis based on immunofluorescence testing, but culture revealed macrolide-resistant Bordetella bronchiseptica. Genetic analysis demonstrated that the child was not infected with a kennel cough vaccine strain, although th...

  2. Conference this! Lead Pipers compare conference experiences

    Directory of Open Access Journals (Sweden)

    Editorial Board

    2010-04-01

    Full Text Available As library travel budgets are increasingly slashed around the country, it’s a tough time for conference-going. In this group post, we compare notes about the conferences we’ve attended, which have been our favorites, and why. We hope this will generate creative ideas on good conferences (online or in-person to look forward to, and maybe offer [...

  3. First interactive conference of young scientists. Book of abstracts

    International Nuclear Information System (INIS)

    This interactive conference of young scientists was realised on the Internet. Conference proceeded in five sections: (1) Cellular metabolism, physiology, molecular biology and genetics; (2) Biotechnology and food technology; (3) The use of instrumental methods in the analysis of biologically important substances; (4) Ecology and environmental science; (5) Open section for students. Relevant papers were included into the database INIS.

  4. Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma : report of the 11th annual conference of the European Mantle Cell Lymphoma Network

    NARCIS (Netherlands)

    Dreyling, Martin; Kluin-Nelemans, Hanneke C; Beà, Sílvia; Klapper, Wolfram; Vogt, Niclas; Delfau-Larue, Marie-Helene; Hutter, Grit; Cheah, Chan; Chiappella, Annalisa; Cortelazzo, Sergio; Pott, Christiane; Hess, Georg; Visco, Carlo; Vitolo, Umberto; Klener, Pavel; Aurer, Igor; Unterhalt, Michael; Ribrag, Vincent; Hoster, Eva; Hermine, Olivier

    2013-01-01

    Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases. Clinically, MCL displays an aggressive course, with a

  5. A novel 1050nm handheld OCT imaging system for pediatric retinoblastoma patients: translation from laboratory bench to clinical study (Conference Presentation)

    Science.gov (United States)

    Nadiarnykh, Oleg; Moll, Annette C.; de Boer, Johannes F.

    2016-03-01

    We demonstrate a novel optical coherence tomography system specifically developed and validated for clinical imaging of retinoblastoma tumors in pediatric patients. The existing treatment options for this malignant tumor of the retina aim at reduction of tumor (re)growth risks, and vision preservation. The choice of optimal treatment strongly depends on skilled and detailed clinical assessment. Currently, the patients at risk are periodically monitored with retinal imaging for possible morphological changes over time, and new tumor seedings, as the existing real-time diagnostic tools are limited. Three-dimensional visualization of tissue layer and microvasculature at improved axial and lateral resolution of interference-based OCT imaging provides sensitivity for detection of vital tumor tissue concurrent with local treatment. Our METC-approved system accommodates for the range of optical parameters of infants' eyes, and uses the 1050nm wavelength to access the deeper choroid layers of retina. The prototype is designed for patients in supine position under general anesthesia, where ergonomic handheld module is connected to fiber-based optical setup via umbilical cord. The system conforms to clinical safety requirements, including fully isolated low-voltage electric circuit. Focusing is performed with a mechanically tunable lens, where resolution is 6 µm axially, and varies with focusing at 10-18µm laterally. We will present optical design, performance limitations, and results of the ongoing clinical study, including the increased OCT diagnostic sensitivity in three dimensions in comparison with the established clinical imaging modalities. We will discuss images of early, active, and treated tumors, as well as follow-up on patients after local and systemic treatments.

  6. The genetic basis of inherited anomalies of the teeth. Part 1: clinical and molecular aspects of non-syndromic dental disorders.

    Science.gov (United States)

    Bailleul-Forestier, Isabelle; Molla, Muriel; Verloes, Alain; Berdal, Ariane

    2008-01-01

    The genetic control of dental development represents a complex series of events, which can very schematically be divided in two pathways: specification of type, size and position of each dental organ, and specific processes for the formation of enamel and dentin. Several genes linked with early tooth positioning and development, belong to signalling pathways and have morphogenesis regulatory functions in morphogenesis of other organs where they are associated with the signalling pathways. Their mutations often show pleïotropic effects beyond dental morphogenesis resulting in syndromic developmental disorders. Some genes affecting early tooth development (MSX1, AXIN2) are associated with tooth agenesis and systemic features (cleft palate, colorectal cancer). By contrast, genes involved in enamel (AMELX, ENAM, MMP20, and KLK4) and dentin (DSPP) structures are highly specific for tooth. Mutations in these genes have been identified as causes of amelogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasias and anomalies of teeth number (hypo-, oligo and anodontia), which only partially overlap with the classical phenotypic classifications of dental disorders. This review of genetic basis of inherited anomalies describes, in this first paper, the molecular bases and clinical features of inherited non-syndromic teeth disorders. And in a second part, the review focus on genetic syndromes with dental involvement. PMID:18499550

  7. Interfacing microbiology and biotechnology. Conference abstracts

    International Nuclear Information System (INIS)

    The Interfacing Microbiology and Biotechnology Conference was attended by over 100 faculty, post-docs, students, and research scientists from the US, Europe, and Latin America. The conference successfully stimulated communication and the dissemination of knowledge among scientists involved in basic and applied research. The focus of the conference was on microbial physiology and genetics and included sessions on C1 metabolism, archaeal metabolism, proteases and chaperones, gene arrays, and metabolic engineering. The meeting provided the setting for in-depth discussions between scientists who are internationally recognized for their research in these fields. The following objectives were met: (1) The promotion of interaction and future collaborative projects among scientists involved in basic and applied research which incorporates microbial physiology, genetics, and biochemistry; (2) the facilitation of communication of new research findings through seminars, posters, and abstracts; (3) the stimulation of enthusiasm and education among participants including graduate and undergraduate students

  8. Interfacing microbiology and biotechnology. Conference abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Maupin, Julia A.

    2001-05-19

    The Interfacing Microbiology and Biotechnology Conference was attended by over 100 faculty, post-docs, students, and research scientists from the US, Europe, and Latin America. The conference successfully stimulated communication and the dissemination of knowledge among scientists involved in basic and applied research. The focus of the conference was on microbial physiology and genetics and included sessions on C1 metabolism, archaeal metabolism, proteases and chaperones, gene arrays, and metabolic engineering. The meeting provided the setting for in-depth discussions between scientists who are internationally recognized for their research in these fields. The following objectives were met: (1) The promotion of interaction and future collaborative projects among scientists involved in basic and applied research which incorporates microbial physiology, genetics, and biochemistry; (2) the facilitation of communication of new research findings through seminars, posters, and abstracts; (3 ) the stimulation of enthusiasm and education among participants including graduate and undergraduate students.

  9. Heterogeneity in the genetic alterations and in the clinical presentation of acrodermatitis enteropathic: Case report and review of the literature.

    Science.gov (United States)

    Ricci, G; Ferrari, S; Calamelli, E; Ricci, L; Neri, I; Patrizi, A

    2016-06-01

    Acrodermatitis enteropathic (AE) is a rare autosomal recessive disorder due to a zinc deficiency and characterized by a classical triad of symptoms: dermatitis, alopecia, and diarrhea. The defective gene is SLC39A4, which encodes a zinc transporter. Nevertheless many abnormalities in SLC39A4 have been relieved, only 50% of patients show alterations. Here is reported the case of an infant with mild and incomplete manifestations of AE, for whom the SLC39A4 genetic test was performed. A novel mutation in SLC39A4 was identified. Zinc replacement improved rapidly the skin lesions. Our case highlights the importance of suspecting this rare condition and to perform the genetic test even in those patients who do not fulfil the classical triad of symptoms. Further efforts should be addressed to identify a more strength correlation between genotype and phenotype of this disorder. PMID:26684640

  10. Points to consider for prioritizing clinical genetic testing services:a European consensus process oriented at accountability for reasonableness

    OpenAIRE

    Severin, Franziska; Borry, Pascal; Cornel, Martina C.; Daniels, Norman; Fellmann, Florence; Victoria Hodgson, Shirley; Howard, Heidi C.; John, Jürgen; Kääriäinen, Helena; Kayserili, Hülya; Kent, Alastair; Koerber, Florian; Kristoffersson, Ulf; Kroese, Mark; Lewis, Celine

    2015-01-01

    Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to...

  11. Agenesis and dysgenesis of the corpus callosum: clinical, genetic and neuroimaging findings in a series of 41 patients.

    Science.gov (United States)

    Schell-Apacik, Chayim Can; Wagner, Kristina; Bihler, Moritz; Ertl-Wagner, Birgit; Heinrich, Uwe; Klopocki, Eva; Kalscheuer, Vera M; Muenke, Maximilian; von Voss, Hubertus

    2008-10-01

    Agenesis of the corpus callosum (ACC) is among the most frequent human brain malformations with an incidence of 0.5-70 in 10,000. It is a heterogeneous condition, for which several different genetic causes are known, for example, ACC as part of monogenic syndromes or complex chromosomal rearrangements. We systematically evaluated the data of 172 patients with documented corpus callosum abnormalities in the records, and 23 patients with chromosomal rearrangements known to be associated with corpus callosum changes. All available neuroimaging data, including CT and MRI, were re-evaluated following a standardized protocol. Whenever feasible chromosome and subtelomere analyses as well as molecular genetic testing were performed in patients with disorders of the corpus callosum in order to identify a genetic diagnosis. Our results showed that 41 patients with complete absence (agenesis of the corpus callosum-ACC) or partial absence (dysgenesis of the corpus callosum-DCC) were identified. Out of these 28 had ACC, 13 had DCC. In 11 of the 28 patients with ACC, the following diagnoses could be established: Mowat-Wilson syndrome (n = 2), Walker-Warburg syndrome (n = 1), oro-facial-digital syndrome type 1 (n = 1), and chromosomal rearrangements (n = 7), including a patient with an apparently balanced reciprocal translocation, which led to the disruption and a predicted loss of function in the FOXG1B gene. The cause of the ACC in 17 patients remained unclear. In 2 of the 13 patients with DCC, unbalanced chromosomal rearrangements could be detected (n = 2), while the cause of DCC in 11 patients remained unclear. In our series of cases a variety of genetic causes of disorders of the corpus callosum were identified with cytogenetic anomalies representing the most common underlying etiology. PMID:18792984

  12. Post-weaning multisystemic wasting syndrome (PMWS) clinical expression under field conditions is modulated by the pig genetic background

    OpenAIRE

    López-Soria, Sergio; Nofrarías, Miquel; Calsamiglia, Maria; Espinal, Anna; Valero, Oliver; Ramírez-Mendoza, Humberto; Mínguez, Almudena; Serrano, José M.; Marín, Óscar; Callén, Antonio; Segalés, Joaquim

    2011-01-01

    ABSTRACT Post-weaning multisystemic wasting syndrome (PMWS) is a worldwide distributed disease of multifactorial origin and porcine circovirus type 2 (PCV2) has been identified as its essential infectious aetiology. Pig genetic background has been pointed to influence disease expression. In the present study, three different boar lines, namely A (100% Pietrain), B (50% Large White x 50% Pietrain) and C (25% Large White x 75% Duroc), were used to inseminate sows from the same geneti...

  13. Agenesis and Dysgenesis of the Corpus Callosum: Clinical, Genetic and Neuroimaging Findings in a Series of 41 Patients

    OpenAIRE

    Schell-Apacik, Chayim Can; Wagner, Kristina; Bihler, Moritz; Ertl-Wagner, Birgit; Heinrich, Uwe; Klopocki, Eva; Kalscheuer, Vera M.; Muenke, Maximilian; von Voss, Hubertus

    2008-01-01

    Agenesis of the corpus callosum (ACC) is among the most frequent human brain malformations with an incidence of 0.5–70 in 10,000. It is a heterogeneous condition, for which several different genetic causes are known, for example, ACC as part of monogenic syndromes or complex chromosomal rearrangements. We systematically evaluated the data of 172 patients with documented corpus callosum abnormalities in the records, and 23 patients with chromosomal rearrangements known to be associated with co...

  14. Genetic Variants in Matrix Metalloproteinase Genes as Disposition Factors for Ovarian Cancer Risk, Survival, and Clinical Outcome

    OpenAIRE

    Yan WANG; Ye, Yuanqing; Lin, Jie; Meyer, Larissa; Wu, Xifeng; Lu, Karen; Liang, Dong

    2013-01-01

    Ovarian cancer is one of the leading female cancers in the United States. Challenges remain in early diagnosis of this deadly disease. Matrix metalloproteinases (MMPs) family genes are paradoxically involved in cancer promotion and suppression. We hypothesize that genetic variants in MMP genes are associated with ovarian cancer development, so they could be potential markers for ovarian cancer diagnosis and prognosis. In this study of 417 ovarian cancer cases and 417 healthy controls, we geno...

  15. Crossed pulmonary arteries: a report on 20 cases with an emphasis on the clinical features and the genetic and cardiac abnormalities.

    Science.gov (United States)

    Babaoğlu, Kadir; Altun, Gürkan; Binnetoğlu, Köksal; Dönmez, Muhammed; Kayabey, Özlem; Anık, Yonca

    2013-01-01

    Crossed pulmonary arteries (CPAs) are a rare abnormality in which the ostium of the left pulmonary artery originates superior to the right pulmonary artery and to its right. Recognition of this rare pathology is important because it generally is accompanied by other congenital heart defects, extracardiac anomalies, and certain genetic problems. To date, only a few cases have been reported, and most of these cases have been associated with complex cardiac abnormalities. The authors detected 20 cases of CPA between June 2009 and November 2012 through their increasing awareness of this anomaly. Approximately 9,250 echocardiograms were performed during this period, and all of them also were checked for this anomaly. This report describes 20 cases of this CPA, with an emphasis on the clinical features and the genetic and cardiac abnormalities. The patients ranged in age from 1 day to 13 years at the time of the initial diagnosis. Four patients had complex cardiac pathologies such as tetralogy of Fallot, truncus arteriosus, transposition of the great arteries, and complete atrioventricular septal defect. Of the 20 patients, 11 had ventricular septal defects, and 12 had atrial septal defects. Pulmonary artery stenosis was detected in 12 (55 %) of the 20 patients. Aortic arch abnormalities such as interrupted aortic arch, right aortic arch, and coarctation of the aorta were detected in six patients. One patient had a left persistent superior vena cava. In 45 % of the cases, an associated genetic syndrome (DiGeorge-, Noonan-, Holt-Oram syndromes, vertebral, anal, cardiac, tracheal, esophageal, renal, limb anomalies [VACTERL] anomalies) was present. These syndromes were diagnosed based on their clinical features. Karyotype and fluorescent in situ hybridization (FISH) analyses for a 22q11 deletion were performed for 11 patients, with 10 patients found to have normal karyotype and FISH results. Only one patient had a 22q11 deletion. Six patients underwent successful operations

  16. Applications for detection of acute kidney injury using electronic medical records and clinical information systems: workgroup statements from the 15(th) ADQI Consensus Conference.

    Science.gov (United States)

    James, Matthew T; Hobson, Charles E; Darmon, Michael; Mohan, Sumit; Hudson, Darren; Goldstein, Stuart L; Ronco, Claudio; Kellum, John A; Bagshaw, Sean M

    2016-01-01

    Electronic medical records and clinical information systems are increasingly used in hospitals and can be leveraged to improve recognition and care for acute kidney injury. This Acute Dialysis Quality Initiative (ADQI) workgroup was convened to develop consensus around principles for the design of automated AKI detection systems to produce real-time AKI alerts using electronic systems. AKI alerts were recognized by the workgroup as an opportunity to prompt earlier clinical evaluation, further testing and ultimately intervention, rather than as a diagnostic label. Workgroup members agreed with designing AKI alert systems to align with the existing KDIGO classification system, but recommended future work to further refine the appropriateness of AKI alerts and to link these alerts to actionable recommendations for AKI care. The consensus statements developed in this review can be used as a roadmap for development of future electronic applications for automated detection and reporting of AKI. PMID:26925245

  17. Pleural subxyphoid drain confers better pulmonary function and clinical outcomes in chronic obstructive pulmonary disease after off-pump coronary artery bypass grafting: a randomized controlled trial

    OpenAIRE

    Solange Guizilini; Marcela Viceconte; Esperança, Gabriel Tavares da M.; Douglas W. Bolzan; Milena Vidotto; Rita Simone L Moreira; Andréia Azevedo Câncio; Gomes, Walter J.

    2014-01-01

    Objective: To evaluate the lung function and clinical outcome in severe chronic obstructive pulmonary disease in patients undergoing off-pump coronary artery bypass grafting with left internal thoracic artery graft, comparing the pleural drain insertion in the intercostal versus subxyphoid region. Methods: A randomized controlled trial. Chronic obstructive pulmonary disease patients were randomized into two groups according pleural drain site: II group (n=27) - pleural drain in intercostal sp...

  18. Emergence of clinical isolates of Escherichia coli producing TEM-1 derivatives or an OXA-1 beta-lactamase conferring resistance to beta-lactamase inhibitors.

    OpenAIRE

    Zhou, X. Y.; Bordon, F; Sirot, D; Kitzis, M D; Gutmann, L

    1994-01-01

    Sixteen Escherichia coli clinical isolates which were resistant to ampicillin and amoxicillin-clavulanate but susceptible to cephalothin were studied. Eight strains showed the presence of a beta-lactamase which comigrates with reference OXA-1 enzyme. The eight other strains produced different TEM-1 derivatives which had in common a higher Km for penicillins and a higher 50% inhibitory concentration for the beta-lactamase inhibitors. By oligotyping and sequencing of PCR products, it was shown ...

  19. Huntington舞蹈病一家系临床遗传学分析%Clinical-Genetic Analysis of the Huntington Chorea

    Institute of Scientific and Technical Information of China (English)

    罗纯

    2012-01-01

    目的 通过分析Huntington舞蹈病一家系临床资料并对症前高风险成员进行再发风险预测,为该病的基因诊断和遗传咨询提供科学依据.方法 全面的家系调查、深入的系谱分析和主动的遗传优生咨询.结果 以先证者为线索深入调查此家系4代39人,家系中有Htington舞蹈病患者7例,3男4女;高风险者7名,需进一步进行基因诊断.结论 此病为常染色体显性遗传病;体现了延迟显性、遗传印记和遗传早现等遗传学特征;对家系高风险者进行婚育指导和症前、孕前、产前诊断对避免患儿的出生具有重要意义.%OBJECTIVE To analyze the clinical data of a Huntington Chorea family and predicting the recurrence risk before symptomatic recurrence for high-risk members, provide scientific basis for genetic disease diagnosis and counseling. METHODS Comprehensive family survey, in-depth genetic pedigree analysis and proactive eugenic counseling were conducted. RESULTS We took the proband as a clue to look into the four generations of a family with 39 people, 7 of them (3 males and 4 females) had Huntington Chorea, another 7 had high risk who were subjects to further genetic diagnosis. CONCLUSION The Huntington Chorea is autosomal dominant inheritance. It features delayed dominance, genetic imprinting, genetic anticipation and other genetic characteristics. For families at high risk, it is critical to provide guidance on marriage and child rearing, pre-pregnancy and prenatal diagnosis in order to avoid the birth of children with the disease.

  20. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the R.T.O.G.-Astro phoenix consensus conference

    Energy Technology Data Exchange (ETDEWEB)

    Roach, M. [California Univ., Dept. of Radiation Oncology, San Francisco, CA (United States); Hanks, G. [Texas Univ., Dept. of Biostatistics and Applied Mathematics, M.D. Anderson Cancer Center, Houston, TX (United States); Thames, H. [Fox Chase Comprehensive Cancer Center, Dept. of Radiation Oncology, Philadelphia, PA (United States); Schellhammer, P. [Eastern Virginia Medical School, Dept. of Urology, Norfolk, VA (United States); Shipley, W.U. [Harvard Medical School, Dept. of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Sokol, G.H. [U.S. Food and Drug Administration, Rockville, MD (United States); Sandler, H. [Michigan Univ., Dept. of Radiation Oncology, Ann Arbor, MI (United States)

    2008-01-15

    In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and back-dating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined 'at call' (not back-dated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to 'adequate follow-up.' To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature. (authors)

  1. Conference summary: Experimnetal

    International Nuclear Information System (INIS)

    The conference is the 1995 International Conference on Strongly Correlated Electron Systems. The summary highlights research on the ''extended'' Doniach model, Kondo insulators, borocarbide superconductors, oxides (including cuprates), other phase transitions, and new materials

  2. The learning conference

    DEFF Research Database (Denmark)

    Ravn, Ib

    2007-01-01

    are active professionals in search of inspiration, and they also want to share knowledge with their peers at the conference. A theory of the conference as a forum for mutual inspiration and human co-flourishing is proposed, as are four design principles for a learning conference: 1. Presentations must...

  3. INFCE plenary conference documents

    International Nuclear Information System (INIS)

    This document consists of the reports to the First INFCE Plenary Conference (November 1978) by the Working Groups a Plenary Conference of its actions and decisions, the Communique of the Final INFCE Plenary Conference (February 1980), and a list of all documents in the IAEA depository for INFCE

  4. Discrepancy in compliance between the clinical and genetic diagnosis of choroidal hypoplasia in Danish Rough Collies and Shetland Sheepdogs

    DEFF Research Database (Denmark)

    Fredholm, Merete; Larsen, R. C.; Jönsson, M.; Söderlund, M. A.; Hardon, T.; Proschowsky, H. F.

    2016-01-01

    Collie eye anomaly (CEA) is a congenital, inherited ocular disorder which is widespread in herding breeds. Clinically, the two major lesions associated with CEA are choroidal hypoplasia (CH) and coloboma, and both lesions are diagnosed based on ophthalmological examination. A 7.8-kb intronic...

  5. Pleural subxyphoid drain confers better pulmonary function and clinical outcomes in chronic obstructive pulmonary disease after off-pump coronary artery bypass grafting: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Solange Guizilini

    2014-12-01

    Full Text Available Objective: To evaluate the lung function and clinical outcome in severe chronic obstructive pulmonary disease in patients undergoing off-pump coronary artery bypass grafting with left internal thoracic artery graft, comparing the pleural drain insertion in the intercostal versus subxyphoid region. Methods: A randomized controlled trial. Chronic obstructive pulmonary disease patients were randomized into two groups according pleural drain site: II group (n=27 - pleural drain in intercostal space; SI group (n=29 - pleural drain in the subxyphoid region. Spirometry values (Forced Vital Capacity - and Forced expiratory volume in 1 second were obtained on preoperative and 1, 3 and 5 postoperative days. Chest x-ray from preoperative until postoperative day 5 (POD5 was performed for monitoring respiratory events, such as atelectasis and pleural effusion. Pulmonary shunt fraction and pain score was evaluate preoperatively and on postoperative day 1. Results: In both groups there was a significant decrease of the spirometry values (Forced Vital Capacity and Forced expiratory volume in 1 second until POD5 (P<0.05. However, when compared, SI group presented less decrease in these parameters (P<0.05. Pulmonary shunt fraction was significantly lower in SI group (P<0.05. Respiratory events, pain score, orotracheal intubation time and postoperative length of hospital stay were lower in the SI group (P<0.05. Conclusion: Subxyphoid pleural drainage in severe Chronic obstructive pulmonary disease patients determined better preservation and recovery of pulmonary capacity and volumes with lower pulmonary shunt fraction and better clinical outcomes on early postoperative off-pump coronary artery bypass grafting.

  6. [Hereditary amyloid cardiomyopathy related to a mutation at transthyretin protein number 111. A clinical, genetic and echocardiographic study of an affected Danish family].

    Science.gov (United States)

    Svendsen, I H; Steensgaard-Hansen, F; Nordvåg, B Y

    1999-09-01

    Amyloidosis is a group of diseases characterized by amyloid deposition in various tissues. The diseases can roughly be divided into hereditary and non-hereditary forms. The hereditary forms are related to a mutation in the serum protein transthyretin which is produced mainly in the liver. The inheritance is autosomal dominant. A family in Denmark has earlier been described as having inherited cardiac amyloidosis with a mutation at amino acid number 111 in the transthyretin protein. The family now has been re-examined because of new diagnostic and therapeutic possibilities. The aims of the study were to identify carriers and non-carriers of the mutant transthyretin methionine 111 linked familial amyloid disease, to detect early signs of the restrictive cardiomyopathy and other clinical manifestations of this disease. Clinical, echocardiographic and genetic examination was carried out. Out of 125 living family members, 99 were available for examination. Twenty-five persons were heterozygous carriers of the mutant transthyretin methionine 111 genotype, while 74 were non-carriers. Eight carriers, all above the age of 35, showed echocardiographic abnormalities suggestive of developing or manifest restrictive cardiomyopathy. Nine carriers had carpal tunnel syndrome as opposed to none of the non-carriers. It is concluded that for early detection of familial amyloid cardiomyopathy, echocardiography is the investigation of choice. The first sign is diastolic dysfunction detected as an abnormal relaxation pattern. Carpal tunnel syndrome appears to be the earliest presenting clinical symptom. Early liver transplantation seems to be curative. PMID:10489791

  7. Development of a database system and image viewer to assist in the correlation of histopathologic features and digital image analysis with clinical and molecular genetic information.

    Science.gov (United States)

    Yagi, Yukako; Riedlinger, Gregory; Xu, Xun; Nakamura, Akira; Levy, Bruce; Iafrate, A John; Mino-Kenudson, Mari; Klepeis, Veronica E

    2016-02-01

    Pathologists are required to integrate data from multiple sources when making a diagnosis. Furthermore, whole slide imaging (WSI) and next generation sequencing will escalate data size and complexity. Development of well-designed databases that can allow efficient navigation between multiple data types is necessary for both clinical and research purposes. We developed and evaluated an interactive, web-based database that integrates clinical, histologic, immunohistochemical and genetic information to aid in pathologic diagnosis and interpretation with nine lung adenocarcinoma cases. To minimize sectioning artifacts, representative blocks were serially sectioned using automated tissue sectioning (Kurabo Industries, Osaka Japan) and selected slides were stained by multiple techniques, (hematoxylin and eosin [H&E], immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]). Slides were digitized by WSI scanners. An interactive relational database was designed based on a list of proposed fields covering a variety of clinical, pathologic and molecular parameters. By focusing on the three main tasks of 1.) efficient management of textual information, 2.) effective viewing of all varieties of stained whole slide images (WSI), and 3.) assistance in evaluating WSI with computer-aided diagnosis, this database prototype shows great promise for multi-modality research and diagnosis. PMID:26778830

  8. Molecular genetics made simple

    Directory of Open Access Journals (Sweden)

    Heba Sh. Kassem

    2012-07-01

    Full Text Available Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients.

  9. International Conference on Physics

    CERN Document Server

    2016-01-01

    OMICS International, (conference series) the World Class Open Access Publisher and Scientific Event Organizer is hosting “International Conference on physics” which is going to be the biggest conference dedicated to Physics. The theme “Highlighting innovations and challenges in the field of Physics” and it features a three day conference addressing the major breakthroughs, challenges and the solutions adopted. The conference will be held during June 27-29, 2016 at New Orleans, USA. Will be published in: http://physics.conferenceseries.com/

  10. Predictive Factors for BRCA1 and BRCA2 Genetic Testing in an Asian Clinic-Based Population.

    Directory of Open Access Journals (Sweden)

    Edward S Y Wong

    Full Text Available The National Comprehensive Cancer Network (NCCN has proposed guidelines for the genetic testing of the BRCA1 and BRCA2 genes, based on studies in western populations. This current study assessed potential predictive factors for BRCA mutation probability, in an Asian population.A total of 359 breast cancer patients, who presented with either a family history (FH of breast and/or ovarian cancer or early onset breast cancer, were accrued at the National Cancer Center Singapore (NCCS. The relationships between clinico-pathological features and mutational status were calculated using the Chi-squared test and binary logistic regression analysis.Of 359 patients, 45 (12.5% had deleterious or damaging missense mutations in BRCA1 and/or BRCA2. BRCA1 mutations were more likely to be found in ER-negative than ER-positive breast cancer patients (P=0.01. Moreover, ER-negative patients with BRCA mutations were diagnosed at an earlier age (40 vs. 48 years, P=0.008. Similarly, triple-negative breast cancer (TNBC patients were more likely to have BRCA1 mutations (P=0.001 and that these patients were diagnosed at a relatively younger age than non-TNBC patients (38 vs. 46 years, P=0.028. Our analysis has confirmed that ER-negative status, TNBC status and a FH of hereditary breast and ovarian cancer (HBOC are strong factors predicting the likelihood of having BRCA mutations.Our study provides evidence that TNBC or ER-negative patients may benefit from BRCA genetic testing, particularly younger patients (<40 years or those with a strong FH of HBOC, in Asian patients.

  11. Association of genetic variants in VEGF-A with clinical recurrence in prostate cancer patients treated with definitive radiotherapy

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor-A (VEGF-A), a key regulator of tumor-induced angiogenesis, is critical for tumor growth and metastasization. The goal of the present study was to evaluate the prognostic value of VEGF single nucleotide polymorphisms (SNPs) and haplotypes for clinical recurrence after definitive radiotherapy for prostate cancer. The association of seven VEGF-A polymorphisms and their haplotypes with clinical recurrence (defined as the occurrence of local recurrence and/or distant metastases) in 496 prostate cancer patients treated with definitive radiotherapy were investigated. Genotypes were determined by 5'-nuclease (TaqMan) assays; haplotypes were analyzed using the Haploview program. Within a median follow-up time of 80 months, 44 patients (9%) developed clinical recurrences. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms (-2578C > A, -2489C > T, -1498C > T, -634G > C, -7C > T) upstream of the coding sequence (CCCCC, ATTGC, CCCGC, ATTGT) and two polymorphisms (936C > T, 1612G > A) downstream of the coding sequence (CA, CG, TG). Carriers of at least 1 copy of the ATTGC haplotype were at higher risk of recurrence (hazard ratio [HR] 3.83; 95%CI 1.48-9.90, p=0.006); for carriers of 2 copies, the HR was 4.85 (95%CI 1.72-13.6; p=0.003). In multivariate analysis, patients harboring at least one copy of the ATTGC haplotype remained at increased risk of recurrence (HR 3.63, 95%CI 1.38-9.55, p=0.009); in patients carrying 2 copies, the HR was 4.72 (95%CI 1.64-13.6, p=0.004). Our findings indicate that the VEGF-A ATTGC haplotype may predict clinical recurrence in prostate cancer patients treated with radiotherapy. (orig.)

  12. Association of genetic variants in VEGF-A with clinical recurrence in prostate cancer patients treated with definitive radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Langsenlehner, T.; Thurner, E.M.; Kapp, K.S. [Medical University of Graz, Department of Therapeutic Radiology and Oncology, Graz (Austria); Renner, W. [Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz (Austria); Gerger, A. [Medical University of Graz, Division of Oncology, Department of Internal Medicine, Graz (Austria); Langsenlehner, U. [GKK Outpatient Department, Division of Internal Medicine, Graz (Austria)

    2014-04-15

    Vascular endothelial growth factor-A (VEGF-A), a key regulator of tumor-induced angiogenesis, is critical for tumor growth and metastasization. The goal of the present study was to evaluate the prognostic value of VEGF single nucleotide polymorphisms (SNPs) and haplotypes for clinical recurrence after definitive radiotherapy for prostate cancer. The association of seven VEGF-A polymorphisms and their haplotypes with clinical recurrence (defined as the occurrence of local recurrence and/or distant metastases) in 496 prostate cancer patients treated with definitive radiotherapy were investigated. Genotypes were determined by 5'-nuclease (TaqMan) assays; haplotypes were analyzed using the Haploview program. Within a median follow-up time of 80 months, 44 patients (9%) developed clinical recurrences. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms (-2578C > A, -2489C > T, -1498C > T, -634G > C, -7C > T) upstream of the coding sequence (CCCCC, ATTGC, CCCGC, ATTGT) and two polymorphisms (936C > T, 1612G > A) downstream of the coding sequence (CA, CG, TG). Carriers of at least 1 copy of the ATTGC haplotype were at higher risk of recurrence (hazard ratio [HR] 3.83; 95%CI 1.48-9.90, p=0.006); for carriers of 2 copies, the HR was 4.85 (95%CI 1.72-13.6; p=0.003). In multivariate analysis, patients harboring at least one copy of the ATTGC haplotype remained at increased risk of recurrence (HR 3.63, 95%CI 1.38-9.55, p=0.009); in patients carrying 2 copies, the HR was 4.72 (95%CI 1.64-13.6, p=0.004). Our findings indicate that the VEGF-A ATTGC haplotype may predict clinical recurrence in prostate cancer patients treated with radiotherapy. (orig.)

  13. Clinical and Translational Implications for the Caveolin Gene Family: Lessons from Mouse Models and Human Genetic Disorders

    OpenAIRE

    Mercier, Isabelle; Jasmin, Jean Francois; Pavlides, Stephanos; Minetti, Carlo; Flomenberg, Neal; Pestell, Richard G.; Frank, Philippe G.; Sotgia, Federica; Lisanti, Michael P.

    2009-01-01

    Here, we review the clinical and translational implications of the caveolin gene family for understanding the pathogenesis of human diseases, including breast and prostate cancers, pulmonary hypertension, cardiomyopathy, diabetes, and muscular dystrophy. Detailed phenotypic analysis of caveolin knock-out mice has served to highlight the crucial role of a caveolin-deficiency in the pathogenesis of many human disease processes. Mutations in the human caveolin genes are associated with a number ...

  14. Genetics of oxacillin resistance in clinical isolates of Streptococcus pneumoniae that are oxacillin resistant and penicillin susceptible.

    OpenAIRE

    Dowson, C G; Johnson, A P; Cercenado, E.; George, R C

    1994-01-01

    It has recently been reported that penicillin-sensitive pneumococci may exhibit reduced susceptibility to oxacillin, resulting in their misclassification as being penicillin resistant by oxacillin disk testing. Intermediate oxacillin resistance (MIC, 1.0 microgram/ml) in three of these apparently unrelated penicillin-susceptible clinical isolates of Streptococcus pneumoniae isolated in the United Kingdom and in four Spanish isolates was shown to be solely due to the acquisition of a gene enco...

  15. Clinical evaluation, biochemistry and genetic polymorphism analysis for the diagnosis of lactose intolerance in a population from northeastern Brazil

    OpenAIRE

    Paulo Roberto Lins Ponte; Pedro Henrique Quintela Soares de Medeiros; Alexandre Havt; Joselany Afio Caetano; Cid, David A C; Mara de Moura Gondim Prata; Alberto Melo Soares; Richard L. Guerrant; Josyf Mychaleckyj; Aldo Ângelo Moreira Lima

    2016-01-01

    OBJECTIVE: This work aimed to evaluate and correlate symptoms, biochemical blood test results and single nucleotide polymorphisms for lactose intolerance diagnosis. METHOD: A cross-sectional study was conducted in Fortaleza, Ceará, Brazil, with a total of 119 patients, 54 of whom were lactose intolerant. Clinical evaluation and biochemical blood tests were conducted after lactose ingestion and blood samples were collected for genotyping evaluation. In particular, the single nucleotide polymo...

  16. Clinical and biochemical signs in Fleckvieh cattle with genetically confirmed Fanconi-Bickel syndrome (cattle homozygous for Fleckvieh haplotype 2).

    Science.gov (United States)

    Burgstaller, Johann; Url, Angelika; Pausch, Hubert; Schwarzenbacher, Hermann; Egerbacher, Monika; Wittek, Thomas

    2016-01-01

    Fanconi-Bickel Syndrome (FBS) is an autosomal recessive disorder of the carbohydrate metabolism, which has been reported in human and some animals (OMIA 000366-9913). In Fleckvieh cattle it is caused by mutations in SLC2A2, a gene encoding for glucose transporter protein 2 (GLUT2), which is primarily expressed in liver, kidney, pancreas and intestines. The causal mutation resides in a previously reported Fleckvieh Haplotype 2 (FH-2). FH-2 homozygous individuals are rare, but due to widespread use of heterozygous bulls in artificial insemination, heterozygous animals are likely to be present in a larger number in the cattle population. Two clinical cases of Fleckvieh cattle with a syndrome resembling the phenotypic appearance of FBS are presented in the present study describing the association between the clinical manifestations of FBS and the postulated frameshift mutation in bovine SLC2A2. Clinical examination showed poor growth, retarded development, polyuria, and polydipsia. Laboratory analyses showed an increased plasma glucose but normal insulin concentration and increased renal glucose excretion. Histopathological examination of kidney and liver samples revealed massively increased liver glycogen storage and nephrosis. Sires of both cases were tested positive for being heterozygous carriers for the same frameshift mutation in SLC2A2 as was originally reported in Fleckvieh cattle. DNA of both cases described was analyzed and Sanger sequencing confirmed homozygosity for the frameshift mutation in SLC2A2. PMID:27169150

  17. Integrating clinical and laboratory data in genetic studies of complex phenotypes: a network-based data management system.

    Science.gov (United States)

    McMahon, F J; Thomas, C J; Koskela, R J; Breschel, T S; Hightower, T C; Rohrer, N; Savino, C; McInnis, M G; Simpson, S G; DePaulo, J R

    1998-05-01

    The identification of genes underlying a complex phenotype can be a massive undertaking, and may require a much larger sample size than thought previously. The integration of such large volumes of clinical and laboratory data has become a major challenge. In this paper we describe a network-based data management system designed to address this challenge. Our system offers several advantages. Since the system uses commercial software, it obviates the acquisition, installation, and debugging of privately-available software, and is fully compatible with Windows and other commercial software. The system uses relational database architecture, which offers exceptional flexibility, facilitates complex data queries, and expedites extensive data quality control. The system is particularly designed to integrate clinical and laboratory data efficiently, producing summary reports, pedigrees, and exported files containing both phenotype and genotype data in a virtually unlimited range of formats. We describe a comprehensive system that manages clinical, DNA, cell line, and genotype data, but since the system is modular, researchers can set up only those elements which they need immediately, expanding later as needed. PMID:9603614

  18. Genetic diversity of Trichomonas vaginalis clinical isolates determined by EcoRI restriction fragment length polymorphism of heat-shock protein 70 genes.

    Science.gov (United States)

    Meade, John C; de Mestral, Jacqueline; Stiles, Jonathan K; Secor, W Evan; Finley, Richard W; Cleary, John D; Lushbaugh, William B

    2009-02-01

    Restriction fragment length polymorphism (RFLP) analysis using a multilocus heat-inducible cytoplasmic heat-shock protein 70 (Hsp70) hybridization probe with EcoRI-digested genomic DNA was used in molecular typing of 129 Trichomonas vaginalis isolates. Results indicate that Trichomonas organisms exhibit considerable polymorphism in their Hsp70 RFLP patterns. Analysis of seven American Type Culture Collection reference strains and 122 clinical isolates, including 84 isolates from Jackson, Mississippi, 18 isolates from Atlanta, Georgia, and 20 isolates from throughout the United States, showed 105 distinct Hsp70 RFLP pattern subtypes for Trichomonas. Phylogenetic analysis of the Hsp70 RFLP data showed that the T. vaginalis isolates were organized into two clonal lineages. These results illustrate the substantial genomic diversity present in T. vaginalis and indicate that a large number of genetically distinct Trichomonas isolates may be responsible for human trichomoniasis in the United States. PMID:19190222

  19. PON1 Q192R genetic variant and response to clopidogrel and prasugrel: pharmacokinetics, pharmacodynamics, and a meta-analysis of clinical outcomes.

    Science.gov (United States)

    Mega, Jessica L; Close, Sandra L; Wiviott, Stephen D; Man, Michael; Duvvuru, Suman; Walker, Joseph R; Sundseth, Scott S; Collet, Jean-Philippe; Delaney, Jessica T; Hulot, Jean-Sebastien; Murphy, Sabina A; Paré, Guillaume; Price, Matthew J; Sibbing, Dirk; Simon, Tabassome; Trenk, Dietmar; Antman, Elliott M; Sabatine, Marc S

    2016-04-01

    Clopidogrel and prasugrel are antiplatelet therapies commonly used to treat patients with cardiovascular disease. They are both pro-drugs requiring biotransformation into active metabolites. It has been proposed that a genetic variant Q192R (rs662 A>G) in PON1 significantly alters the biotransformation of clopidogrel and affects clinical outcomes; however, this assertion has limited support. The relationship between this variant and clinical outcomes with prasugrel has not been studied. We genotyped PON1 Q192R in 275 healthy subjects treated with clopidogrel or prasugrel and 2922 patients with an ACS undergoing PCI randomized to treatment with clopidogrel or prasugrel in the TRITON-TIMI 38 trial. A meta-analysis was performed including 13 studies and 16,760 clopidogrel-treated patients. Among clopidogrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.62) or change in platelet aggregation (P = 0.51). Consistent with these results, in clopidogrel-treated patients in TRITON-TIMI 38, there was no association between Q192R and the rates of CV death, myocardial infarction, or stroke (RR 11.2 %, QR 8.6 %, and QQ 9.3 %; P = 0.66) or stent thrombosis (RR 2.4 %, QR 0.7 %, and QQ 1.6 %, P = 0.30), with patients with the putative at-risk Q variant having numerically lower event rates. Likewise, among prasugrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.88), change in platelet aggregation (P = 0.97), or clinical outcomes (P = 0.72). In a meta-analysis, the Q variant was not significantly associated with MACE (QQ vs. RR 1.22, 95 % CI 0.84-1.76) or stent thrombosis (QQ vs. RR OR 1.36, 95 % CI 0.77-2.38). Furthermore, when restricted to the validation studies, the OR (95 % CI) for MACE and stent thrombosis were 0.99 (0.77-1.27) and 1.23 (0.74-2.03), respectively. In the present study, the Q192R genetic variant in PON1 was not associated with the pharmacologic or clinical

  20. AINSE's 40th anniversary conference. Conference handbook

    International Nuclear Information System (INIS)

    Highlights of 40 years of activity of the Australian Institute of Nuclear Science and Engineering (AINSE) were the main focus of this conference. Topics covered include nuclear physics, plasma physics, radiation chemistry, radiation biology, neutron diffraction, nuclear techniques of analysis and other relevant aspects of nuclear science and technology. The conference handbook contains the summaries of the 78 papers and posters presented and the list of participants