Genetic analysis of Brugada syndrome and congenital long-QT syndrome type 3 in the Chinese

BACKGROUND Brugada syndrome and congenital long-QT syndrome (LQTS) type 3 (LQT3) are 2 inherited conditions of abnormal cardiac excitability characterized clinically by an increased risk of ventricular tachyarrhythmias. SCN5A gene that encodes the cardiac sodium channel α subunit is responsible for the 2 diseases, and more work is needed to improve correlations between SCN5A genotypes and associated clinical syndromes. METHODS AND RESULTS Four patients diagnosed as having Brugada syndrome, 9 patients suspected to have Brugada syndrome, and 3 LQTS patients suspected to be LQT3 without mutations in KCNQ1 and HERG participated in the study. DNA samples from these patients were analyzed using direct sequencing. One patient with Brugada syndrome had 2 novel mutations, V95I and A1649V. The former was identified in the N-terminus of SCN5A and the latter was in the DIVS4/S5 linker of SCN5A. One patient suspected to have Brugada syndrome had a mutation, delF1617, in the DIIIS3/S4 linker of SCN5A. A novel mutation in the C-terminus of SCN5A, delD1790, was found in a patient with LQT3. No other mutations of SCN5A were found in the remaining patients. These 4 mutations were not detected in 50 unrelated control subjects. CONCLUSIONS Two novel and a reported SCN5A mutations were found in Chinese patients with Brugada syndrome, and a novel SCN5A mutation was found in a Chinese patient with LQT3.