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

Neubauer, Jaqueline; Haas, Cordula; Bartsch, Christine; Medeiros Domingo, Argelia; Berger, Wolfgang (2016). Post-mortem whole-exome sequencing (WES) with a focus on cardiac disease-associated genes in five young sudden unexplained death (SUD) cases. International journal of legal medicine, 130(4), pp. 1011-1021. Springer 10.1007/s00414-016-1317-4

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Medeiros Domingo, Argelia

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0937-9827

Publisher:

Springer

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Argelia Medeiros Domingo

Date Deposited:

10 May 2017 15:33

Last Modified:

01 Aug 2021 02:30

Publisher DOI:

10.1007/s00414-016-1317-4

PubMed ID:

26846766

Uncontrolled Keywords:

Cardiac diseases; Molecular autopsy; Sudden unexplained death; Whole-exome sequencing

BORIS DOI:

10.7892/boris.94934

URI:

https://boris.unibe.ch/id/eprint/94934

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