Presence of hypertrophic cardiomyopathy related gene mutations and clinical manifestations in Vietnamese patients with hypertrophic cardiomyopathy

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is associated primarily with pathogenic mutations in sarcomeric genes. The aim of this study was to identify the prevalence and distribution of disease-causing mutations in HCM-associated genes and the genotype-phenotype relationship in Vietnamese patients with HCM. Methods and Results: Genetic testing was performed by next-generation sequencing in 104 unrelated probands for 23 HCM-related genes and in 57 family members for the mutation(s) detected. Clinical manifestations were recorded for genotype-phenotype correlation analysis. Mutation detection rate was 43.4%. Mutations in MYBPC3 accounted for 38.6%, followed by TPM1 (20.5%), MYH7 (18.2%), TNNT2 (9.1%), TNNI3 (4.5%) and MYL2 (2.3%). A mutation in GLA associated with Fabry disease was found in 1 patient. A mutation in TPM1 (c.842T>C, p.Met281Thr) was identified in 8 unrelated probands (18.2%) and 8 family members from 5 probands. Genotype-positive status related to MYH7, TPM1, and TNNT2 mutations was associated with severe clinical manifestations. MYH7-positive patients displayed worse prognosis compared with MYBPC3-positive patients. Interestingly, TPM1 c.842T>C mutation was associated with high penetrance and severe HCM phenotype. Conclusions: We report for the first time the prevalence of HCM-related gene variants in Vietnamese patients with HCM. MYH7, TPM1, and TNNT2 mutations were associated with unfavorable prognosis.