Nicole Hellenthal1, Anna Gaertner-Rommel2, Bärbel Klauke2, Lech Paluszkiewicz2, Markus Stuhr3, Thoralf Kerner4, Martin Farr2, Klaus Püschel1, Hendrik Milting2. 1. Universitätsklinikum Hamburg Eppendorf, Institut für Rechtsmedizin, Butenfeld 34, D-22529 Hamburg, Germany. 2. Herz- und Diabeteszentrum NRW, Universitätsklinik der Ruhr-Universität Bochum, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, Georgstr. 11, D-32545 Bad Oeynhausen, Germany. 3. Berufgenossenschaftliches Unfallkrankenhaus Hamburg, Akademisches Lehrkrankenhaus der Universität zu Lübeck und der Medizinischen Fakultät der Universität Hamburg, Abteilung für Anästhesie, Intensiv- und Rettungsmedizin, Zentrum für Schmerztherapie, Bergedorfer Str. 10, D-21033 Hamburg, Germany. 4. Asklepios Klinikum Harburg, Abteilung für Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie, Eißendorfer Pferdeweg 52, D-21075 Hamburg, Germany.
Abstract
AIMS: Coronary artery disease accounts for the majority of sudden cardiac deaths (SCD) in the older population whereas cardiomyopathies and arrhythmogenic abnormalities predominate in younger SCD victims (<35 years) with a significant genetic component. The elucidation of the pathogenetic cause of death might be relevant for the prevention of further deaths within affected families. Aim of this study was to determine the portion of underlying genetic heart diseases among unexplained putative SCD cases from a large German forensic department. METHODS AND RESULTS: We included 10 forensic cases of sudden unexplained death (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was analysed by next generation panel sequencing of 174 candidate genes for channelopathies and cardiomyopathies. Cardiological examinations, genetic counselling, and subsequent genetic testing were offered to all affected families. We identified within 1 year 10 cases of SUD among 172 forensic cases. Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD cases. Subsequent selective screening of family members revealed two additional mutation carriers. CONCLUSION: The study provides strong evidence that molecular genetics improves the post mortem diagnosis of fatal genetic heart diseases among SUD victims. Molecular genetics should be integrated in forensic and pathological routine practice. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Coronary artery disease accounts for the majority of sudden cardiac deaths (SCD) in the older population whereas cardiomyopathies and arrhythmogenic abnormalities predominate in younger SCD victims (<35 years) with a significant genetic component. The elucidation of the pathogenetic cause of death might be relevant for the prevention of further deaths within affected families. Aim of this study was to determine the portion of underlying genetic heart diseases among unexplained putative SCD cases from a large German forensic department. METHODS AND RESULTS: We included 10 forensic cases of sudden unexplained death (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was analysed by next generation panel sequencing of 174 candidate genes for channelopathies and cardiomyopathies. Cardiological examinations, genetic counselling, and subsequent genetic testing were offered to all affected families. We identified within 1 year 10 cases of SUD among 172 forensic cases. Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD cases. Subsequent selective screening of family members revealed two additional mutation carriers. CONCLUSION: The study provides strong evidence that molecular genetics improves the post mortem diagnosis of fatal genetic heart diseases among SUD victims. Molecular genetics should be integrated in forensic and pathological routine practice. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Ivan Gando; Nori Williams; Glenn I Fishman; Barbara A Sampson; Yingying Tang; William A Coetzee Journal: Forensic Sci Int Date: 2019-05-29 Impact factor: 2.395