家族性肥厚型心肌病患者MYBPC3基因突变筛查

A molecular screening strategy based on cardiac myosin binding protein C genes in China patients with familial hypertrophic cardiomyopathy

目的:研究中国汉族人群家族性肥厚型心肌病(FHCM)患者的致病基因突变位点,分析其基因型与表型关系。方法:对6个家系先证者行肌球连接蛋白-C基因(MYBPC3)筛查,聚合酶链反应扩增其MYBPC3基因13、15-16、26、及27号功能区外显子片断,双脱氧末端终止法测序。对阳性结果者家系中其他成员及健康对照组同一位置筛查,分析患者基因型及临床表型特点。结果:在2个家系中,同时发现MYBPC3基因Val896Met杂合突变,而健康对照组同一位置未见异常,2家系中共6人携带此突变,其中发病5例;该突变可能为我国汉人FHCM家系中首次发现。结论:MYBPC3是我国汉族FHCM患者的常见致病基因;MYBPC3基因Val896Met突变所致肥厚型心肌病外显率高、临床症状出现较晚、进展缓慢、出现明显年龄依赖性特点,为一种良性突变。

Objective：Familial hypertrophic cardiomyopathy （FHCM） is a form of cardiomyopathy with an autosomal dominant inherited disease,which is caused by mutations in at least one of the sarcomeric protein genes. Mutations in the myosin binding protein C genes （MYBPC3） are the more common cause of HCM. This study was to reveal the disease-causing gene mutations in Chinese population with FHCM,and to analyze the correlation between the genotype and phenotype. Method：We sequenced exons 13,15-16,26 and 27 of the MYBPC3 gene in 6 families with hypertrophic cardiomyopathy （HCM） from the region of Anhui province in China; Genomic DNA was amplified,and fragments were directly sequenced. Each DNA variant found in the patients was also analyzed in 80 healthy controls through automatic sequencing. Result：The mutation of V896M in two Chinese families with HCM was detected for the first time in China. With a G→G/A transversion in nucleotide 16750 of the MYBPC3 gene,the replacement of valine by methionine,took place at amino acid residue 896. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy. There was no obstruction in the left ventricular outflow tract in all patients. In two families,a total of 5 individuals were diagnosed HCM and 1 of them were healthy man. The DNA variant was not detected in 80 healthy controls.Conclusion：The mutation of V896M in MYBPC3 is a benign type. Moreover,the heart function of the people evidently more deteriorative when their age are more older. The mutation has been reported in the first in China.