心脏型肌钙蛋白T基因14035c>t突变导致家族性肥厚型心肌病的临床表型分析  

Family hypertrophic cardiomyopathy caused by a 14035c>t mutation in cardiac troponin T gene

作　　者：王曙霞[1] 邹玉宝[1] 傅春燕[1] 宋雷[1] 王虎[1] 王继征[1] 宋晓东[1] 陈敬洲[1] 惠汝太 

机构地区：[1]中国医学科学院中国协和医科大学 心血管病研究所 阜外心血管病医院 中-德分子医学研究室 教育部心血管病基因与临床研究重点实验室,北京100037

出　　处：《中华医学杂志》2007年第6期371-374,共4页National Medical Journal of China

基　　金：北京市自然科学基金(704001)

摘　　要：目的研究中国人肥厚型心肌病(HCM)致病基因,分析基因型与临床表型的关系。方法在一个 HCM 家系中进行心脏型肌钙蛋白 T 基因(TNNT2)、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。结果在该家系接受家系凋查的10例对象中4例携带 TNNT2 14035c>t(R130C)突变,全部于40岁之前发病,外显率100%。正常对照组同一位置未见异常,该突变位点使 TNNT2基因第10号外显子130位的精氨酸变为半胱氨酸,先证者及其两兄长皆以心功能不全表现为主,先证者的两位兄长在我们随访过程中发生猝死。MYH7及 MYBPC3基因未发现突变。结论 TNNT2基因14035c>t 突变是该 HCM 家系的致病突变。其携带者的临床表型较恶。对于临床表型较恶,猝死发生率较高 HCM 家系有必要进行 TNNT2的突变筛查。Objective To study the disease-causing gene mutation in Chinese patients with familial hypertrophic cardiomyopathy （FHC） and to analyze the correlation between the genotype and the phenotype. Methods Peripheral blood samples were collected from 40 members from a family affected with FHC, and 120 healthy volunteers. PCR was performed to analyze the exons and flanking introns of the cardiac troponin T gene （TNNT2）, β-myosin heavy chain gene （MYH7）, and myosin-binding protein C gene （MYBPC3） and the products were sequenced. The clinical data including symptom, physical examination, echocardiography and electrocardiography were collected. Results A 14035c 〉 t mutation, which causes a missense mutation （R130C） in exon 10 of TNNT2 gene were identified in 4 family members, including the proband, female, aged 53, with the onset at the age of 30. The 4 persons with the 14035c 〉 t mutation, all FHC patients, presented left ventricular dysfunction with a penetrance of 100%. Two of the patients died of sudden cardiac death during follow-up. No mutation was identified in the MYH7 and MYBPC3 genes. Conclusion The 14035c 〉 t mutation of TNNT2 gene is the causal mutation of FHC which is associated with malignant phenotype with a penetrance of 100%. It is a reasonable procedure in HCM patients with malignant phenotype to screen mutation in the TNNT2 gene.

关 键 词：心肌病 肥大型 肌钙蛋白T 突变 

分 类 号：R542.2[医药卫生—心血管疾病]