汉族家族性肥厚型心肌病患者的MYH7基因R663H、E924K突变

目的研究中国人家族性肥厚型心肌病(HCM)的致病基因突变位点,分析基因型与临床表型的相互关系。方法对5个家族性HCM的先证者进行β-肌球蛋白重链基因(β-MHC)扫描,聚合酶链反应(PCR)扩增其功能区外显子片段,双脱氧末端终止法测序。对阳性测序结果者进行家系中其他成员筛查,并分析患者临床表型特点。结果在其中2个家系中分别发现R663H、E924K杂合突变,而正常对照组同一位置未见异常,E924K在我国HCM患者中首次发现。结论β-MHC为我国家族性HCM的致病基因之一。其临床表型的异质性提示多因素参与了HCM的发生及外显。

Mutations in beta myosin heavy chain gene: two mutations in Chinese with familial hypertrophic cardiomyopathy and the correlation between the genotype and phenotype

OBJECTIVE: To study the disease-causing gene mutation in Chinese with hypertrophic cardiomyopathy (HCM), and to analyze the correlation between the genotype and phenotype. METHODS: Samples of peripheral blood were collected from five Chinese patients with HCM in whose families at least 2 HCM patients existed. The exon in the functional regions of the beta myosin heavy chain gene (beta-MHC) were amplified with PCR and the products were sequenced. The relation between the genotype and phenotype was analyzed. RESULTS: Two mutations were first identified. Eighty controls were normal in the genetic test. CONCLUSION: beta-MHC may be the main disease-causing gene. Two mutations have different phenotypes. In one family, the identical mutation has different phenotypes and prognoses. The heterogeneity of phenotype suggests that multiple factors be involved in the pathogenesis.