β-肌球蛋白重链基因与肥厚型心肌病临床表型关系的研究

Mutation analysis of beta myosin heavy chain gene in hypertrophic cardiomyopathy families

目的研究肥厚型心肌病（hypertrophic cardiomyopathy，HCM）的主要致病基因β-肌球蛋白重链基因（beta—myosin heavy chain gene，MYH7）的突变位点，探寻基因型与表型的关系。方法扩增3个HCM家系成员的MYH7基因第3、5、7～9、11～16、18～23外显子序列，进行直接测序分析，应用软件与标准序列比对，确定可能的突变位点。结果发现其中1个家系MYH7基因第14外显子存在Thr441Met突变，正常对照组相同位置未见异常。3个家系均发现多个同义突变位点。结论在中国汉族人群中发现MYH2基因Thr441Met突变，该突变位于β-肌球蛋白重链头部肌动蛋白结合位点，可能是HCM的致病突变。HCM具有遗传异质性，多种因素可能参与其发生和发展过程。

Objective To detect the gene mutations of beta-myosin heavy chain gene （MYHT）in Chinese pedigrees with hypertrophic cardiomyopathy （ HCM）, and to analyze the correlation between the genotype and phenotype. Methods Exons 3,5,7-9,11-16 and 18-23 of the MYH7 gene were amplified with PCR in three Chinese pedigrees with HCM. The products were sequenced. Sequence alignment between the detected and the standard sequences was performed. Results A missense mutation of Thr441Met in exon 14 was identified in a pedigree, which was not detected in the controls. Several synonymous mutations of MYH7 gene were detected in the three pedigrees. Conclusion The mutation of Thr441Met,loeated in the aetin binding domain of the globular head, was first identified in Chinese. It probably caused the HCM. HCM is a heterogeneous disease. Many factors are involved in the process of its occurrence and development.