In silico validation revealed the role of SCN5A mutations and their genotype–phenotype correlations in Brugada syndrome

Autor: Hung Manh Pham, Duy Phuong Dang, Thanh Dat Ta, Thi Phuong Le, Dinh Phong Phan, Hoai An Trinh, Tuan Viet Tran, Thi Lan Anh Luong, Ha Minh Nguyen, The‐Hung Bui, Thinh Huy Tran, Thanh Van Ta, Van‐Khanh Tran
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecular Genetics & Genomic Medicine, Vol 11, Iss 12, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2324-9269
DOI: 10.1002/mgg3.2263
Popis: Abstract Background Brugada syndrome (BrS) is a rare genetic disease that causes sudden cardiac death (SCD) and arrhythmia. SCN5A pathogenic variants (about 30% of diagnosed patients) are responsible for BrS. Aims Lack of knowledge regarding molecular characteristics and the correlation between genotype and phenotype interfere with the risk stratification and finding the optimal treatment in Vietnam. Therefore, we identified SCN5A variants and evaluated the genotype–phenotype correlation of BrS on 117 Vietnamese probands. Materials and Methods The clinical characteristics and blood samples of BrS patients were collected. To determine SCN5A variants, Sanger sequencing was conducted, and subsequently, these variants were analyzed by bioinformatic tools. Results In this cohort, the overall rate of detected variants in SCN5A was 25.6%, which could include both pathogenic and benign variants. In genetic testing, 21 SCN5A variants were identified, including eight novels and 15 published variants. Multiple bioinformatic tools were used to predict variant effect with c.551A>G, c.1890+14G>A, c.3338C>T, c.3578G>A, and c.5484C>T as benign, while other variants were predicted as disease‐causing. The family history of SCD (risk ratio [RR] = 4.324, 95% CI: 2.290–8.269, p
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