Detection of mutations in symptomatic patients with hypertrophic cardiomyopathy in Taiwan

Abstract Background Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder associated with sudden death, heart failure, and stroke. The aim of the present study was to evaluate the prevalence and types of mutations in symptomatic patients with HCM in Taiwan. Methods Thirty-eight HCM index patients (mean age 60 ± 16 years) underwent systematic mutation screening of eight sarcomeric genes: β-myosin heavy chain ( MYH7 ), myosin-binding protein C ( MYBPC3 ), troponin T ( TNNT2 ), troponin I ( TNNI3 ), myosin ventricular regulatory light chain 2 ( MYL2 ), myosin ventricular essential light chain 1 ( MYL3 ), α-tropomyosin ( TPM1 ), and cardiac α-actin ( ACTC ), using direct DNA sequencing. In silico programs predicted damaging amino acids. In the positive families, genotype–phenotype correlation studies were done. Results Overall, 13 mutations were identified in 13 index patients (34.2%). The three most frequently mutated genes were MYH7 , MYBPC3 , and TNNT2 . One patient carried double mutations. Five mutations ( MYH7 R147S; MYBPC3 R597Q; MYBPC3 W1007R; TNNI3 E124Q; MYL3 R63C) were novel; all were missense mutations. Analysis using in silico tools showed near consensus to classify these five novel mutations as pathological. Family pedigree analysis showed the presence of cosegregation in at least two affected members in each proband family, but incomplete penetrance in young family members with a positive genotype. Conclusions We identified 13 HCM pedigrees, including 5 carrying novel mutations and 1 with a double mutation. The three most commonly mutated genes were MYH7 , MYBPC3 , and TNNT2 . These results, together with genetic counseling, could lead to earlier diagnosis and better management of family members at risk of HCM.