Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting

• Published in: European journal of human genetics : EJHG Vol. 24; no. 12; pp. 1797 - 1802
• Main Authors: Christiansen, Sofie Lindgren, Hertz, Christin Løth, Ferrero-Miliani, Laura, Dahl, Morten, Weeke, Peter Ejvin, LuCamp, Ottesen, Gyda Lolk, Frank-Hansen, Rune, Bundgaard, Henning, Morling, Niels
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2016
• Subjects: Adolescent; Adult; Autopsy; Cardiomyopathies - genetics; Cardiomyopathies - pathology; Channelopathies - genetics; Channelopathies - pathology; Child; Child, Preschool; Coronary heart disease; Death, Sudden; Defibrillators; Deoxyribonucleic acid; DNA; Female; Forensic Genetics; Forensic medicine; Forensic science; Genetic Loci; Genetic variance; Heart diseases; Humans; Infant; Male; Middle Aged; Mutation; Nucleotide sequence; Psychotropic drugs; Studies; Denmark
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/ejhg.2016.118

In forensic medicine, one-third of the sudden deaths remain unexplained after medico-legal autopsy. A major proportion of these sudden unexplained deaths (SUD) are considered to be caused by inherited cardiac diseases. Sudden cardiac death (SCD) may be the first manifestation of these diseases. The purpose of this study was to explore the yield of next-generation sequencing of genes associated with SCD in a cohort of SUD victims. We investigated 100 genes associated with cardiac diseases in 61 young (1-50 years) SUD cases. DNA was captured with the Haloplex target enrichment system and sequenced using an Illumina MiSeq. The identified genetic variants were evaluated and classified as likely, unknown or unlikely to have a functional effect. The criteria for this classification were based on the literature, databases, conservation and prediction of the effect of the variant. We found that 21 (34%) individuals carried variants with a likely functional effect. Ten (40%) of these variants were located in genes associated with cardiomyopathies and 15 (60%) of the variants in genes associated with cardiac channelopathies. Nineteen individuals carried variants with unknown functional effect. Our findings indicate that broad genetic investigation of SUD victims increases the diagnostic outcome, and the investigation should comprise genes involved in both cardiomyopathies and cardiac channelopathies.