Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: Implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing

摘要: Objectives The purpose of this study was to determine the prevalence and spectrum nonsynonymous polymorphisms (amino acid variants) in cardiac sodium channel among healthy subjects. Background Pathogenic mutations gene, SCN5A , cause approximately 15 20% Brugada syndrome (BrS1), 5 10% long QT (LQT3), 2 5% sudden infant death syndrome. Methods Using single-stranded conformation polymorphism, denaturing high-performance liquid chromatography, and/or direct DNA sequencing, mutational analysis protein-encoding exons performed on 829 unrelated, anonymous subjects: 319 black, 295 white, 112 Asian, 103 Hispanic. Results In addition four known common (R34C, H558R, S1103Y, R1193Q), relatively ethnic-specific were identified: R481W, S524Y, P1090L, V1951L. Overall, 39 distinct missense variants (28 novel) elucidated. Nineteen (49%) found only black cohort. Only seven (18%) localized transmembrane-spanning domains. Four (F1293S, R1512W, V1951L cited previously as BrS1-causing S1787N published a possible LQT3-causing mutation) identified Conclusions This provides first comprehensive determination subjects from ethnic groups. compendium is critical for proper interpretation genetic testing an essential hit list targets future functional studies whether or not any these mediate susceptibility arrhythmias setting either drugs disease.