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01-07-2016 | Original Article

Post-mortem whole-exome sequencing (WES) with a focus on cardiac disease-associated genes in five young sudden unexplained death (SUD) cases

Authors: Jacqueline Neubauer, Cordula Haas, Christine Bartsch, Argelia Medeiros-Domingo, Wolfgang Berger

Published in: International Journal of Legal Medicine | Issue 4/2016

Abstract

Sudden death of healthy young adults in the absence of any medical reason is generally categorised as autopsy-negative sudden unexplained death (SUD). Approximately 30 % of all SUD cases can be explained by lethal sequence variants in cardiac genes causing disturbed ion channel functions (channelopathies) or minimal structural heart abnormalities (cardiomyopathies). The aim of this study was to perform whole-exome sequencing (WES) in five young SUD cases in order to identify potentially disease-causing mutations with a focus on 184 genes associated with cardiac diseases or sudden death. WES analysis enabled the identification of damaging-predicted cardiac sequence alterations in three out of five SUD cases. Two SUD victims carried disease-causing variants in long QT syndrome (LQTS)-associated genes (KCNH2, SCN5A). In a third case, WES identified variants in two genes involved in mitral valve prolapse and thoracic aortic aneurism (DCHS1, TGFβ2). The genome of a fourth case carried several minor variants involved in arrhythmia pointing to a multigene influence that might have contributed to sudden death. Our results confirm that post-mortem genetic testing in SUD cases in addition to the conventional autopsy can help to identify familial cardiac diseases and can contribute to the identification of genetic risk factors for sudden death.

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Title: Post-mortem whole-exome sequencing (WES) with a focus on cardiac disease-associated genes in five young sudden unexplained death (SUD) cases
Authors: Jacqueline Neubauer
Cordula Haas
Christine Bartsch
Argelia Medeiros-Domingo
Wolfgang Berger
Publication date: 01-07-2016
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Legal Medicine / Issue 4/2016
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-016-1317-4

At a glance: The STEP trials

Springer Medicine

Post-mortem whole-exome sequencing (WES) with a focus on cardiac disease-associated genes in five young sudden unexplained death (SUD) cases

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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