title: Post-mortem review and genetic analysis of sudden unexpected death in epilepsy (SUDEP) cases.
abstract: Sudden unexpected death in epilepsy (SUDEP) is the most frequent epilepsy-related cause of death and is characterized by an absence of any identifiable cause of death at post-mortem, suggesting an underlying arrhythmogenic predisposition. This study sought to identify SUDEP cases in a review of post-mortem records and to undertake genetic studies in key familial long QT syndrome (LQTS) genes. All autopsies performed from 1993-2009 at a forensic centre in Sydney, Australia were reviewed and SUDEP cases identified. DNA was extracted from post-mortem blood and the three most common LQTS genes, ie, KCNQ1, KCNH2 (HERG) and SCN5A, were amplified and analyzed. Sixty-eight SUDEP cases were identified (mean age of 40 ± 16 years). Genetic analysis revealed 6 (13%) non-synonymous (amino acid changing) variants in KCNH2 (n = 2) and SCN5A (n = 4), all previously reported in LQTS patients. Specifically, KCNH2 Arg176Trp and SCN5A Pro1090Leu were identified once in SUDEP cases and absent in control alleles. Both DNA variants have been previously identified in the pathogenesis of LQTS. The cause of SUDEP is currently unknown. Our results indicate that investigation of key ion channel genes should be pursued in the investigation of the relationship between epilepsy and sudden death.
authors.affiliation: Agnes Ginges Centre for Molecular Cardiology, Centenary Institute. Sydney Medical School, University of Sydney, Australia.
authors.forename: Emily
authors.initials: E
authors.lastname: Tu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bagnall
authors.forename: Johan
authors.initials: J
authors.lastname: Duflou
authors.forename: Christopher
authors.initials: C
authors.lastname: Semsarian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D002648:Child; D002675:Child, Preschool; D003645:Death, Sudden / Q000209:etiology*; D000072237:ERG1 Potassium Channel; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000235:genetics; D008297:Male; D008875:Middle Aged; D062553:NAV1.4 Voltage-Gated Sodium Channel; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015222:Sodium Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels