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目的研究中国人肥厚型心肌病致病基因,分析基因型与临床表型的关系。方法在一肥厚型心肌病家系中进行心脏型肌球蛋白结合蛋白 C 基因(MYBPC3)和β-肌球蛋白重链基因(MYH7)突变筛查,利用聚合酶链反应(PCR)扩增其功能区的外显子片段,双脱氧末段终止法测序。家系调查资料包括临床表现、体格检查、心脏超声和心电图。结果在该家系27例有血缘关系的研究对象中9例携带 MYBPC3 13261 G>A(G758D)突变,正常对照组同一位置未见异常。该突变位点是 MYBPC3基因第23号外显子的甘氨酸突变为天冬氨酸,其中2例携带者发病,一例表现为心室扩大,左室射血分数减低等扩张型心肌病样表现,伴室间隔不对称肥厚,厚度为14 mm,另外一例患者为典型的肥厚型心肌病表现。MYH7基因未发现突变。结论 MYBPC3基因13261 G>A 突变是该肥厚型心肌病家系的致病突变,其外显率为22%,其中一例患者表现为肥厚型心肌病的扩张相,MYBPC3基因 G758D 突变可能是肥厚型心肌病进展为扩张型心肌病样改变的原因之一。对临床表现为扩张型心肌病的患者进行家族史调查及基因检查十分必要。
Objective To study the pathogenic genes of hypertrophic cardiomyopathy in Chinese and to analyze the relationship between genotype and clinical phenotype. Methods Mutations in cardiac myosin-binding protein C (MYBPC3) and MYH7 genes in a hypertrophic cardiomyopathy family were screened and their functions were amplified by polymerase chain reaction (PCR) Region exon fragment, dideoxy end-stop method sequencing. Pedigree survey data included clinical manifestations, physical examination, echocardiography and cardiogram. Results Nine of the 27 clandestine families in the pedigree carried the MYBPC3 13261 G> A (G758D) mutation, while no abnormality was found in the same place in the normal control group. The site of mutation was the mutation of glycine to aspartate in exon 23 of MYBPC3 gene, of which 2 carriers were carriers of disease. One case showed dilated cardiomyopathy-like manifestation such as enlarged ventricles, decreased left ventricular ejection fraction, Interval asymmetric hypertrophy, a thickness of 14 mm, another case of typical hypertrophic cardiomyopathy performance. MYH7 gene found no mutation. Conclusions The 13261 G> A mutation of MYBPC3 gene is a causative mutation in the hypertrophic cardiomyopathy pedigree. The penetrance of MYBPC3 gene is 22%. One case showed the dilatation phase of hypertrophic cardiomyopathy. The MYBPC3 gene G758D mutation may be hypertrophic myocardium Disease progression is one of the causes of dilated cardiomyopathy-like changes. Family history and genetic tests are essential for patients with clinical manifestations of dilated cardiomyopathy.