Abstract 12238: Comprehensive Genotyping for Scn5a and Related Genes in the Chinese Han Population With Sunds
Background: Reported for nearly 100 years, sudden unexplained nocturnal death syndrome (SUNDS) remains an enigma to both forensic pathologists and physicians. Previous epidemiological, clinical, and pilot genetic studies have suggested that SUNDS is most likely a disease allelic to Brugada syndrome (BrS). We performed postmortem molecular autopsy to address the spectrum and the role of genetic abnormalities in the cardiac sodium channel and several associated proteins in SUNDS victims.
Methods: Genomic DNA was extracted from blood samples of 123 SUNDS from medicolegal autopsy cases and 104 controls in southern China to screen BrS associated genes including SCN5A, MOG1, GPD1-L, and SCN1B-SCN4B (encoding cardiac sodium channel β subunits) using PCR and direct sequencing.
Results: In SCN5A we identified a total of 10 mutations: R121Q (2 cases), V95I, R367H, R1512W, and V1098L (1 case each), all reported previously, and R513H, D870H, V1202M, V1764D, and S1937F (1 case, all novel). In β subunits we identified 3 mutations: in β1 V138I (3 cases, novel), and T189M (2 cases, previously reported), and A195T (1 case, novel). None of the mutations were detected in the controls. No non-synonymous mutants were found in MOG1, GPD1-L, SCN1B, and SCN4B. All these mutations carriers were negative for genetic screening in CPVT and LQTS-susceptibility genes RyR2, KCNQ1, KCNH2, KCNE1, and KCNE2.
Conclusions: This first comprehensive genotyping for SCN5A and related genes in the Chinese Han population with SUNDS discovered 13 mutations, 7 of them novel, in 17 cases, which suggests cardiac sodium channel dysfunction might account for the pathogenesis of 13% of SUNDS in southern China.
- © 2013 by American Heart Association, Inc.