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.
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Acknowledgements
We thank Francisc-Raul Kantor and Carina Grøntved Jønck for bioinformatics support, and Eva Tonnesen for technical support in the laboratory. For the screening of variants among Danish controls, we thank LuCamp, The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (www.lucamp.org), and the Novo Nordisk Foundation Center for Basic Metabolic Research, which is an independent Research Center at the University of Copenhagen partially supported by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). This work was supported by Ellen and Aage Andersen’s Foundation and The AP Møller Foundation.
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Christiansen, S., Hertz, C., Ferrero-Miliani, L. et al. Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting. Eur J Hum Genet 24, 1797–1802 (2016). https://doi.org/10.1038/ejhg.2016.118
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DOI: https://doi.org/10.1038/ejhg.2016.118
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