Novel mutations of cardiac troponin T in Chinese patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To screen the cardiac troponin T (TNNT2) mutations in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the potential link between the genotype and the phenotype.</p><p><b>METHODS</b>Clinical features of 100 probands with HCM and some family members were evaluated, 200 unrelated normal subjects served as control. The exons and flanking introns of TNNT2 were amplified with PCR and direct sequencing was used to screen TNNT2 mutations/polymorphisms.</p><p><b>RESULTS</b>Two novel missense mutations were detected in 2 HCM patients: R92W and R286H. These 2 mutations were not found in 200 non-HCM controls. A five-basepair insertion/deletion polymorphism in intron 3 of TNNT2 was identified in this HCM cohort but was not related to the phenotype.</p><p><b>CONCLUSIONS</b>Two missense mutations, R92W and R286H, were found in 2/100 patients with HCM, TNNT 2 mutation is relatively low in Chinese patients with HCM.</p>

Novel MYBPC3 mutations in Chinese patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To screen the MYBPC3 gene mutations in Han Chinese patients with hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>Sixty-six patients with HCM were enrolled for the study. The exons in the functional regions of MYBPC3 were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>Four novel mutations and four common polymorphisms were identified in this patient cohort. A Lys301fs mutation in exon10 was evidenced in a H30, and when he was 47 years old, he had the chest tightness, shortness of breath with septal hypertrophy of 18.7mm; a Asp463stop mutation in exon17 was detected in a H48, he was 24 years old 24-year-old when a medical examination showed ventricular septal hypertrophy of 15.4 mm; both Gly523Arg mutation in exon18 and Tyr847His mutation in exon26 were found in a H53 with onset age 36 years old, feeling chest tightness after excise and his ventricular septal hypertrophy was 27 mm that time. MYBPC3 mutations occurred in 4.5% patients in this cohort. These mutations were not found in 100 non-HCM control patients.</p><p><b>CONCLUSION</b>MYBPC3 mutation is presented in a small portion of Han Chinese patients with HCM.</p>

Analysis of MYH7, MYBPC3 and TNNT2 gene mutations in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study was to screen the disease-causing gene mutations and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>There are 91 family members from these 10 pedigrees and 5 members were normal mutated carriers, 23 members were HCM patients (14 male) aged from 1.5 to 73 years old. The functional regions of myosin heavy chain gene (MYH7), cardiac myosin-binding protein C (MYBPC3) and cardiac troponin T gene (TNNT2) were screened with PCR and direct sequencing technique. Clinical information from all patients was also evaluated in regard to the genotype.</p><p><b>RESULTS</b>Mutations were found in 5 out of 10 pedigrees. Mutations in MYH7 (Arg663His, Glu924Lys and Ile736Thr) were found in 3 pedigrees and 3 patients from these pedigrees suffered sudden death at age 20-48 years old during sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation (Arg502Trp and splicing mutation IVS27 + 12C > T) and 1 with novel frame shift mutation (Gly347fs) and the latter pedigree has sudden death history. No mutation was identified in TNNT2.</p><p><b>CONCLUSIONS</b>Although the Han Chinese is a relatively homogeneous ethnic group, different HCM gene mutations were responsible for familiar HCM suggesting the heterogeneity nature of the disease-causing genes and HCM MYH7 mutations are associated with a higher risk of sudden death in this cohort. Furthermore, identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of familiar HCM.</p>