Genetic background and clinical phenotype in a Vietnamese cohort with Brugada syndrome: A whole exome sequencing study

Objectives The aim of this study was to report the spectrum of genetic variations and clinical phenotype in a Vietnamese cohort with confirmed Brugada syndrome (BrS) using the whole exome sequencing (WES). Methods Fifty patients with confirmed BrS were included in this study. Genomic DNA samples were extracted from peripheral blood and conducted for WES. The variants were annotated using ANNOVAR. The variants in the 13 reported genes associated with BrS were filtered, predicted the functional impact using eight computational tools, and classified according to the 2015 ACMG guidelines. Results Arrhythmic events were documented in one-fifth of the participants. Twenty-four probands were identified to carry 36 variants in 13 genes. Majority of the variants in our study was SCN5A variants (9/36 variants, 25%), followed by KCNH2 variants (5/36 variants, 14%). The prevalence of SCN5A carriers was 16%; while the prevalence of minor gene carriers was less than 10%. Nine novel missense variants were identified, including four missense SCN5A variants (p.E901D, p.F853L, p.L377F, and p.H184R), two missense ANK2 variants (p.S2845L and V1497L), one missense CACNA1C variant (M1126V), one missense DSP variant (p.K478N), and one intron splicing JUP variant (c.1498-5G>C). Conclusion Our study underscores the primary significance of the SCN5A gene in BrS, as indicated by variant prevalence, carrier rates, pathogenicity per ACMG classification, in silico predictions, and its correlation with clinical phenotypes. Longitudinal study with larger sample size, pedigree, Sanger sequence confirmation, and functional analysis is recommended.