KHẢO SÁT TÍNH SINH BỆNH CỦA ĐỘT BIẾN GEN SCN5A TRONG HỘI CHỨNG BRUGADA

Abstract

Introduction: Brugada syndrome is an inherited cardiac arrhythmia that causes sudden death. Mutations in the SCN5A gene, which codes for the sodium channel, have been identified as a cause of Brugada syndrome. Because there were several difficulties on conducting in vivo-model experiments and systematic clinical trials, the pathogenesis of novel mutations in the SCN5A gene, which was an important step in the establishment of genotype-phenotype relationship,was in progress in in silico models. Objectives: To determine SCN5A gene mutations in Brugada syndrome patients and to investigate the pathogenicity of these mutations. Subjects and research methods: case series study was carried on Brugada syndrome patients at hospitals in Ho Chi Minh City and Hanoi. The disease was diagnosed according to the European Heart Rhythm Society 2015 criteria. Mutations were identified by Sanger sequencing. Using protein function prediction softwares to investigate the pathogenicity of the mutations. Results: There were 50 patients participating in the study. 14 mutations were detected in the SCN5A gene of 14 patients. These were 10 different types of mutations, of which 4 are novel mutationsthat have not been published in genetic databases. When predicting pathogenicity using bioinformatic softwares, 80% are pathogenic and likely pathogenic. The pathological phenotypes of 12 patients carrying pathogenic or likely pathogenic mutations were described concurrently. Conclusion: The study investigated and determined the pathogenicity for 10 types of SCN5A gene mutations detected in Brugada syndrome patients, using the bioinformatic softwares. Although this isan appropriate approach at this time, it is necessary to have more statistically significant associations between mutations and patients phenotypes to confirm the pathogenicity.