Publications (293)2122.15 Total impact
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Article: Multiplex Targeted High Throughput Sequencing for mendelian cardiac disorders.
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ABSTRACT: Mendelian cardiomyopathies and arrhythmias are characterized by an important genetic heterogeneity, rendering Sanger sequencing very laborious and expensive. As a proof of concept we explored multiplex targeted high-throughput sequencing as a fast and cost-efficient diagnostic method for individuals suffering from mendelian cardiac disorders. We designed a DNA capture assay including all exons from 130 genes involved in cardiovascular mendelian disorders and analysed simultaneously 4 samples by multiplexing. Two patients had familial hypertrophic cardiomyopathy (HCM) and 2 patients suffered from long-QT syndrome (LQTS). In patient 1 with HCM, we identified two known pathogenic missense variants in the two most frequently mutated sarcomeric genes MYH7 and MYBPC. In patient 2 with HCM, a known acceptor splice site variant in MYBPC3 was found. In patient 3 with LQTS, two missense variants in the genes SCN5A and KCNQ were identified. Finally, in patient 4 with LQTS a known missense variant was found in MYBPC3 which usually is mutated in patients with cardiomyopathy. Our results demonstrate that multiplex targeted High-Throughput-Sequencing works as an efficient and cost-effective tool for molecular diagnosis of heterogeneous disorders in clinical practice and offers new insights in the pathogenesis of these complex diseases.Clinical Genetics 04/2013; · 3.13 Impact Factor -
Article: Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.
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ABSTRACT: This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1-deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the β-isoform of neurexin-1 and increased head size, as was recently published in four cases with a deletion involving the C-terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2013; · 3.70 Impact Factor -
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Top co-authors
Top Journals
- Human Mutation (13)
- Human Genetics (11)
- Genome Research (11)
- The American Journal of Human Genetics (10)
- Nature (10)
Institutions
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1996–2013
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University of Geneva
- • Department of Genetic Medicine and Development (GEDEV)
- • Division of Gastroenterology and Hepatology
- • Department of Cell Biology
Carouge, GE, Switzerland -
Kantonsspital Baselland Bruderholz
Basel, BS, Switzerland
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2012
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Institute of Genetics & Hospital for Genetic Diseases
Hyderābād, State of Andhra Pradesh, India -
The Nebraska Medical Center
Omaha, NE, USA
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2011
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National Research Council - Italy
Roma, Latium, Italy -
Creighton University
- Department of Pharmacology
Omaha, NE, USA
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2007–2009
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Duke University
- • Center for Human Genome Variation
- • Institute for Genome Sciences and Policy
Durham, NC, USA -
University of Minnesota Duluth
Duluth, MN, USA -
Tel Aviv University
- Department of Psychiatry
Tel Aviv, Tel Aviv, Israel -
Inselspital, Universitätsspital Bern
Bern, BE, Switzerland -
University of Pennsylvania
Philadelphia, PA, USA
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2005–2009
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Wellcome Trust Sanger Institute
Cambridge, ENG, United Kingdom -
The Walter and Eliza Hall Institute of Medical Research
- Division of Immunology
Melbourne, Victoria, Australia -
Stanford Medicine
- Center for Interdisciplinary Brain Sciences Research
Stanford, CA, USA
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2008
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Academy of Athens
Athens, Attiki, Greece
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2007–2008
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University of Oslo
Oslo, Oslo, Norway
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2006–2008
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University Pompeu Fabra
- Center for Genomic Regulation (CRG)
Barcelona, Catalonia, Spain
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2005–2008
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Université de Lausanne
- • Département de microbiologie fondamentale
- • Centre intégratif de génomique
Lausanne, VD, Switzerland
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2006–2007
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United Arab Emirates University
Al ‘Ayn, Abu Zaby, United Arab Emirates
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2005–2007
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University Hospital of Lausanne
Lausanne, VD, Switzerland
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1990–2006
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Johns Hopkins University
- Department of Pediatrics
Baltimore, MD, USA
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2004
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University-Hospital of Padova
Padova, Veneto, Italy
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2003
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Leids Universitair Medisch Centrum
Leiden, South Holland, Netherlands
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2002
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Stanford University
- Department of Psychiatry and Behavioral Sciences
Stanford, CA, USA
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1999
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University of California, Irvine
- Department of Pediatrics
Irvine, CA, USA
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1998
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Università degli Studi di Genova
Genova, Liguria, Italy
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1992
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Johns Hopkins Medicine
Baltimore, MD, USA
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1991
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University of Pittsburgh
- Division of Medical Genetics
Pittsburgh, PA, USA
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