国人肥厚型心肌病患者肌球蛋白结合蛋白C基因Gly507 Arg和Pro1208fs突变的不同临床表型

目的 研究中国人肥厚型心肌病的致病基因,阐述基因型-表型的关系.方法 对21例无血缘关系的肥厚型心肌病先证者进行心脏型肌球蛋白结合蛋白C基因(cMYBPC3)突变筛查,利用聚合酶链反应(PCR)扩增其功能Ⅸ的外显子片段,双脱氧末端终止法测序.家系资料调查包括临床表现、体格检查、心脏超声和心电图.结果 在2例先证者中发现基因突变.其中H12为家族性肥厚型心肌病的先证者,为cMYBPC3基因第32号外显子Pro1208fs突变,即在人类基因组第21078处发生了碱基C的缺失.H19为散发肥厚型心肌病患者,在cMYBPC3基因第17号外显子发现Gly507Arg突变,即在人类基因组第10 966处发生了碱基G→A互换,使甘氨酸变为精氨酸.H12发病年龄较晚,临床表现轻微.H19为24岁青年男性,超声心动图示肥厚累及部位广泛,室壁较厚,舒张功能减退明显,左心房明显增大.80例正常对照未发现异常.结论 cMYBPC3基因Gly507Arg和Pro1208fs突变可能致国人肥厚型心肌病.

Link between cardiac myosin binding protein-C gene mutation of Pro1208fs and Gly507Arg and hypertrophic cardiomyopathy in Chinese patients

Objective To detect gene mutations associated with hypertrophic cardiomyopathy (HCM) in Chinese patients and possible correlations between genotype and phenotype. Methods Twenty-one unrelated patients with hypertrophic cardiomyopathy were studied. The clinical data including symptoms, physical examination, echocardiography and electrocardiography were collected. The full ecoding exons of cardiac myosin-binding protein C gene (cMYBPC3) were amplified with PCR and the products were sequenced. Results Two mutations were identified in probands from two families. One mutation was frame shift mutation Pro1208fs in the exon 32 of the cMYBPC3 gene. Pro1208fs mutation was identified in a 59 years old female patient with familial hypertrophic cardiomyopathy. Symptom onset was late and a favorable clinical course was evidenced in this patient. Another mutation was missence mutation Gly507Arg in the exon 17 of the MYBPC3 gene identified in a 24 years old male patient. Diffuse thickness of left ventricular wall, impaired diastolic function and enlarged left atria were evidenced in echocardiography. No mutation was identified in the 80 control healthy individuals. Conclusion cMYBPC3 might be the disease-causing genes in Chinese patients with hypertrophic cardiomyopathy.