Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases

TY - JOUR

T1 - Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases

AU - Hellenthal, Nicole

AU - Gaertner-Rommel, Anna

AU - Klauke, Bärbel

AU - Paluszkiewicz, Lech

AU - Stuhr, Markus

AU - Kerner, Thoralf

AU - Farr, Martin

AU - Püschel, Klaus

AU - Milting, Hendrik

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1093/europace/euw247

DO - 10.1093/europace/euw247

M3 - SCORING: Journal article

C2 - 29016939

VL - 19

SP - 1881

EP - 1890

JO - EUROPACE

JF - EUROPACE

SN - 1099-5129

IS - 11

ER -