遗传 ›› 2009, Vol. 31 ›› Issue (5): 485-488.doi: 10.3724/SP.J.1005.2009.00485

• 研究报告 • 上一篇    下一篇

心脏肌球蛋白重链基因c.1273G>A突变与肥厚型心肌病的关联分析

王虎;邹玉宝;宋雷;王继征;孙凯;宋晓东;高硕;张禅那;惠汝太   

  1. 中国医学科学院阜外心血管病医院, 中-德分子医学研究室, 心血管病基因与临床研究教育部重点实验室, 北京100037
  • 收稿日期:2008-09-30 修回日期:2008-10-25 出版日期:2009-05-10 发布日期:2009-05-10
  • 通讯作者: 惠汝太

The genotype-phenotype correlation of the MYH7 gene c.1273G > A mutation in familial hypertrophic cardiomyopathy

WANG Hu;ZOU Yu-Bao;SONG Lei;WANG Ji-Zheng;SUN Kai;SONG Xiao-Dong;GAO Shuo;ZHANG Chan-Na;HUI Ru-Tai   

  1. Sino-German Laboratory for Molecular Medicine, Fu Wai Cardiovascular Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China
  • Received:2008-09-30 Revised:2008-10-25 Online:2009-05-10 Published:2009-05-10
  • Contact: HUI Ru-Tai

摘要: 为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, 文章在1个中国汉族HCM家系中进行心脏肌钙蛋白T (TNNT2) 基因、心脏肌球蛋白结合蛋白C (MYBPC3) 基因和心脏β-肌球蛋白重链 (MYH7) 基因的突变筛查, 聚合酶链式反应(PCR)扩增基因功能区外显子片段并对PCR产物进行测序分析。结果表明: 在该家系接受调查的7名成员中有4名成员携带MYH7基因c.1273G>A杂合突变, 该突变位点位于MYH7基因的14号外显子并使425位的甘氨酸(Gly)转换为精氨酸(Arg)。该突变首次在国内HCM家系中发现, 突变携带者的临床表型在家系内部呈现明显的异质性。该家系成员TNNT2及MYBPC3基因未发现突变且正常对照组相同位置未发现异常。MYH7基因是我国家族性 HCM的致病基因之一, 携带c.1273G>A突变的肥厚型心肌病患者临床表型差异明显, 提示可能有其它因素参与了肥厚型心肌病的发展过程。

关键词: 肥厚型心肌病, 肌球蛋白重链, 突变

Abstract: To investigate the genotype-phenotype correlation in Chinese familial hypertrophic cardiomyopathy (HCM), peripheral blood samples were collected from 7 members of a Chinese HCM family, and 120 normal sub-jects were recruited as control. The full encoding exons and flanking sequences of the cardiac troponin T (TNNT2) gene, beta-myosin heavy chain (MYH7) gene and myosin binding protein C (MYBPC3) gene were amplified and the products were sequenced directly to detect the mutations. A missense mutation, c.1273G>A, was identified in exon 14 of the MYH7 gene in 4 members of the Chinese HCM family, which resulted a glycine (Gly) to arginine (Arg) exchange at amino acid residue 425. The 425th glycine amino acid residue is highly conservative across the different species. The clinical phenotypes among the family members who carried this mutation presented significant individual differences. The c.1273G>A mutation of the MYH7 gene might be the causal mutation of the familial HCM. The het-erogeneity of phenotypes suggested that multiple factors may be involved in the pathogenesis of HCM.