title: Postmortem molecular analysis of KCNQ1 and SCN5A genes in sudden unexplained death in young Australians.
abstract: The cause of sudden death in young people remains unknown in up to 50% of postmortem cases. Mutations in the ion channel genes are known to cause primary arrhythmogenic disorders such as long QT and Brugada syndromes, which can present with sudden cardiac death and a negative autopsy. In this study, 59 sudden unexplained deaths occurring in Australians aged </=35 years with a negative autopsy, from 1994-2002, were studied. Genomic DNA was extracted from paraffin-embedded tissues. Genetic analysis of the KCNQ1 and SCN5A genes was performed using denaturing high-performance liquid chromatography and direct DNA sequencing. Nine DNA sequence variants were identified in the KCNQ1 gene and 9 sequence variants were identified in the SCN5A gene. In total, 23 out of 59 cases were found to have at least one DNA variant in KCNQ1 or SCN5A, of which one, H558R in the SCN5A gene, caused an amino acid substitution. None of the DNA variants were determined to be disease causing as they were also identified in control populations. In conclusion, no disease-causing mutations were found in the KCNQ1 or SCN5A genes in this cohort. A more selective screening approach, including only individuals with a clinical or family history of arrhythmogenic disorders, may yield greater success in identifying disease-causing mutations in cohorts of young individuals who have died suddenly.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Doolan
authors.forename: Neil
authors.initials: N
authors.lastname: Langlois
authors.forename: Christine
authors.initials: C
authors.lastname: Chiu
authors.forename: Jodie
authors.initials: J
authors.lastname: Ingles
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lind
authors.forename: Christopher
authors.initials: C
authors.lastname: Semsarian
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001315:Australia / Q000453:epidemiology; D001344:Autopsy; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D003645:Death, Sudden / Q000453:epidemiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels