心脏肌球蛋白结合蛋白C基因S236G新突变致肥厚型心肌病表型研究

A novel hot-spot mutation S236G in the cardiac myosin binding protein C gene in Chinese patient with hypertrophic cardiomyopathy

目的研究中国人肥厚型心肌病的致病基因突变位点，寻找国人特有的热点突变并分析基因型与临床表型的相互关系。方法在100例肥厚型心肌病患者以及120名健康对照者中进行心脏型肌球蛋白结合蛋白C（Mx／BPC3）基因突变筛查，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。结果在3例肥厚型心肌病患者中发现MYBPC3基因第6号外显子第706位碱基由T转换为C，结果导致第236位的丝氨酸（Ser，S）转变为甘氨酸（Gly，G），正常对照组相同位置未发现异常。该突变在西方人中未见报道，携带该突变的肥厚型心肌病患者呈现不同的临床表型。结论首次在中国人肥厚型心肌病患者中发现MYBPC3基因S236G突变，其在中国人肥厚型心肌病患者中占有一定的比例，是热点突变之一。

Objective To identify the disease-causing gene mutations and to reveal the relationship between the genotype and the phenotype in Chinese patients with hypertrophic cardiomyopathy （ HCM ）. Methods One hundred unrelated patients with HCM and 120 controls were enrolled in this study. The full encoding exons and flanking sequences of the cardiac myosin binding protein C gene （ MYBPC3 ） were amplified with PCR and the products were sequenced. Results A novel missense mutation c. 706T 〉 C was identified in exon 6 of MYBPC3 gene in three HCM patients, which resulted a Serine （S） to Glycine （G） exchange at amino acid residue 236 （S236G）. The clinical phenotypes of the three patients were different （2 obstructive HCM, 1 non-obstructive HCM）. The 120 controls were normal in the genetic test. Conclusions The novel S236G mutation in MYBPC3 gene was a hot-spot mutation in Chinese patients with HCM.