title: Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting.
abstract: 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.
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sofie Lindgren
authors.initials: SL
authors.lastname: Christiansen
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christin Løth
authors.initials: CL
authors.lastname: Hertz
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Laura
authors.initials: L
authors.lastname: Ferrero-Miliani
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Dahl
authors.affiliation: The Department of Cardiology, Laboratory of Molecular Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Peter Ejvin
authors.initials: PE
authors.lastname: Weeke
authors.affiliation: LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark.
authors.lastname: LuCamp
authors.affiliation: Section of Forensic Pathology, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gyda Lolk
authors.initials: GL
authors.lastname: Ottesen
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rune
authors.initials: R
authors.lastname: Frank-Hansen
authors.affiliation: The Unit for Inherited Cardiac Diseases, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Bundgaard
authors.affiliation: Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Morling
mesh_terms: D000293:Adolescent; D000328:Adult; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D053447:Channelopathies / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003645:Death, Sudden; D005260:Female; D053803:Forensic Genetics; D056426:Genetic Loci; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation