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01-07-2018 | Original Article

Exome analysis in 34 sudden unexplained death (SUD) victims mainly identified variants in channelopathy-associated genes

Authors: Jacqueline Neubauer, Maria Rita Lecca, Giancarlo Russo, Christine Bartsch, Argelia Medeiros-Domingo, Wolfgang Berger, Cordula Haas

Published in: International Journal of Legal Medicine | Issue 4/2018

Abstract

Sudden cardiac death (SCD) is one of the major causes of mortality worldwide, mostly involving coronary artery disease in the elderly. In contrary, sudden death events in young victims often represent the first manifestation of undetected genetic cardiac diseases, which remained without any symptoms during lifetime. Approximately 30% of these sudden death cases have no definite cardiac etiology after a comprehensive medicolegal investigation and are therefore termed as sudden unexplained death (SUD) cases. Advances in high-throughput sequencing approaches have provided an efficient diagnostic tool to identify likely pathogenic variants in cardiovascular disease-associated genes in otherwise autopsy-negative SUD cases. The aim of this study was to genetically investigate a cohort of 34 unexplained death cases by focusing on candidate genes associated with cardiomyopathies and channelopathies. Exome analysis identified potentially disease-causing sequence alterations in 29.4% of the 34 SUD cases. Six (17.6%) individuals had variants with likely functional effects in the channelopathy-associated genes AKAP9, KCNE5, RYR2, and SEMA3A. Interestingly, four of these six SUD individuals were younger than 18 years of age. Since the total SUD cohort of this study included five children and adolescents, post-mortem molecular autopsy screening indicates a high diagnostic yield within this age group. Molecular genetic testing represents a valuable approach to uncover the cause of death in some of the SUD victims; however, 70–80% of the cases still remain elusive, emphasizing the importance of additional research to better understand the pathological mechanisms leading to a sudden death event.

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Title: Exome analysis in 34 sudden unexplained death (SUD) victims mainly identified variants in channelopathy-associated genes
Authors: Jacqueline Neubauer
Maria Rita Lecca
Giancarlo Russo
Christine Bartsch
Argelia Medeiros-Domingo
Wolfgang Berger
Cordula Haas
Publication date: 01-07-2018
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Legal Medicine / Issue 4/2018
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-018-1775-y

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Exome analysis in 34 sudden unexplained death (SUD) victims mainly identified variants in channelopathy-associated genes

Abstract

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Abstract

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