title: Genetic analysis of sudden unexplained death: a multidisciplinary approach.
abstract: Each year infants, children and young adults die suddenly and unexpectedly. In many cases the cause of death can be elucidated by medico-legal autopsy, however, a significant number of these cases remain unexplained despite a detailed postmortem investigation and are labeled as sudden unexplained death (SUD). Post-mortem genetic testing, so called molecular autopsy, revealed that primary arrhythmogenic disorders including long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) may account for a certain number of these cases. Because of the inheritance of these diseases, close relatives of the deceased may also at potential risk of carrying fatal cardiac disorders. Therefore, advanced diagnostic analyses, genetic counseling and interdisciplinary collaboration should be integral parts of clinical and forensic practice. In the present study, we performed mutation analyses of the major genes causing cardiac channelopathies in 15 SUD cases. In four cases we found putative pathogenic mutations in cardiac ion channel genes. Clinical and genetic examination of family members of SUD victims was also performed and affected family members were identified. This study demonstrates that molecular genetic screening needs to become an inherent part of the postmortem examination. This will enhance the ability of screening family members of SUD victims who may be at risk. The present data also illustrate that detection and follow up of familial cases of sudden death is challenging and requires a close multidisciplinary collaboration between different medical disciplines, with great responsibility for the forensic pathologist.
authors.affiliation: Institute of Legal Medicine, University of Frankfurt, Kennedyallee 104, D-60596 Frankfurt am Main, Germany. kauferstein@em.uni-frankfurt.de
authors.forename: Silke
authors.initials: S
authors.lastname: Kauferstein
authors.forename: Nadine
authors.initials: N
authors.lastname: Kiehne
authors.forename: Tina
authors.initials: T
authors.lastname: Jenewein
authors.forename: Stephanie
authors.initials: S
authors.lastname: Biel
authors.forename: Marnie
authors.initials: M
authors.lastname: Kopp
authors.forename: Rainer
authors.initials: R
authors.lastname: König
authors.forename: Damir
authors.initials: D
authors.lastname: Erkapic
authors.forename: Markus
authors.initials: M
authors.lastname: Rothschild
authors.forename: Thomas
authors.initials: T
authors.lastname: Neumann
mesh_terms: D000293:Adolescent; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000235:genetics; D003299:Cooperative Behavior; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005260:Female; D053803:Forensic Genetics; D005817:Genetic Counseling; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010375:Pedigree; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D055815:Young Adult
chemical_list: C489457:KCNJ2 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024661:Potassium Channels, Inwardly Rectifying; D019837:Ryanodine Receptor Calcium Release Channel; C568320:SCN5A protein, human