家族性肥厚型心肌病MYH7基因突变的筛查与分析

目的 研究家族性肥厚型心肌病(hypertrophic cardiomyopathy,HCM)的主要致病基因β肌球蛋白重链(beta-myosin heavy chain gene,MYH7)突变,并分析基因型与表型的关系.方法 对3个HCM家系成员的MYH7基因3～23号外显子及附近上下游序列采用DHPLC及直接测序分析.结果 在其中一个家系中发现MYH7基因14号外显子中存在Thr441Met突变,该突变曾经在一莱恩远端肌病患者中发现,而在中国人中是首次发现.另外两个家系也发现有不同位点的突变.结论 MYH7基因在HCM家系中具有较高的突变率,不同突变基因型以及基因突变携带个体在临床表型上有所差异.采取基因突变检测和分析,有利于HCM家族成员的诊断、患病风险预测及疾病早期预防和治疗.

Abstract：

Objective To detect gene mutations on beta-myosin heavy chain gene MYH7 in 3 Chinese families with hypertrophic cardiomyopathy ( HCM), and to analyze the correlation between genotype and phenotype. Methods A denaturing high-performance liquid chromatography (DHPLC) and sequencing mutation screening of the exons ( exon3-23 ) coding for MYH7 gene were performed in 3 Chinese families with HCM. Results In this study, we identified several mutations in MYHT. A mutation of Thr441 Met previously reported in a patient with Laing distal myopathy was first identified in one Chinese pedigree. Conclusion This study illustrated the high frequency of mutation in MYH7 gene in Chinese HCM families. Different mutations and carriers of the MYH7 gene present phenotypic heterogeneity. Mutation screening and analysis in HCM family could therefore facilitate the early HCM diagnosis and would be helpful for the prediction, prevention and early treatment of HCM linked with MYH7 gene mutation.

Screening and analysis of the mutations on beta-myosin heavy chain gene in 3 Chinese families with hypertrophic cardiomyopathy

Objective To detect gene mutations on beta-myosin heavy chain gene MYH7 in 3 Chinese families with hypertrophic cardiomyopathy ( HCM), and to analyze the correlation between genotype and phenotype. Methods A denaturing high-performance liquid chromatography (DHPLC) and sequencing mutation screening of the exons ( exon3-23 ) coding for MYH7 gene were performed in 3 Chinese families with HCM. Results In this study, we identified several mutations in MYHT. A mutation of Thr441 Met previously reported in a patient with Laing distal myopathy was first identified in one Chinese pedigree. Conclusion This study illustrated the high frequency of mutation in MYH7 gene in Chinese HCM families. Different mutations and carriers of the MYH7 gene present phenotypic heterogeneity. Mutation screening and analysis in HCM family could therefore facilitate the early HCM diagnosis and would be helpful for the prediction, prevention and early treatment of HCM linked with MYH7 gene mutation.