心脏型肌钙蛋白Ⅰ基因4693 C／T突变导致家族性心尖部肥厚型心肌病  

Apical Family Hypertrophic Cardiomyopathy Caused by a 4693C/T Mutation in Cardiac Troponin Ⅰ Gene

作　　者：王曙霞[1] 邹玉宝[1] 傅春燕[1] 王继征[1] 宋雷[1] 张伟丽[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：《中国分子心脏病学杂志》2006年第5期253-256,共4页Molecular Cardiology of China

基　　金：北京市自然科学基金委员会资助2004年重大项目(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HCM家系中进行心脏型肌钙蛋白Ⅰ基因(TNNI3)、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调查的8例有亲缘关系的对象中5例携带TNNI3 4693C/T(R145W)突变,全部发病,外显率100%。正常对照组同一位置未见异常,该突变位点使TNN13基因第7号外显子143位的精氨酸变为色氨酸,5例患者中4例表现为心尖部肥厚为主,1例表现为室间隔基底段肥厚为主,临床症状表现为轻微的胸闷。MYH7、MYBPC3及TNNT2基因未发现突变。结论TNNI3基因4693C/T突变是该HCM家系的致病突变,其外显率为100%。其携带者主要表现为心尖部肥厚为主,临床表型较好。对于心尖部肥厚为主的HCM家系有必要进行TNNI3的突变筛查。Objective To study the disease-causing gene mutation in Chinese patients with hyper- trophic cardiomyopathy(HCM)and to analyze the correlation of the genotype and the phenotype.Methods One family affected with HCM were chosen for the study.The full encoding exons and flanking sequences of cardiac troponin I gene(TNNI3),β-myosin heavy chain gene(MYH7),myosin-binding protein C gene (MYBPC3)and troponin T gene(TNNT2)were amplified with PCR and the products were sequenced.The clinical data including symptom,physical examination,echocardiography and electrocardiography were collect- ed.Results We identified a 4693C/T mutation,which causes a missense mutation(R145W)in exon 7 of TNNI3 in 5 family members.The penetrance is 100%.Four mutation carriers manifested with apical hypertro-w phy measured by echoeardiography and presented with mild chest pain.No mutation was identified in MYH7, MYBPC3 and TNNT2 gene.Conclusion The 4693C/T mutation of TNNI3 is the causal mutation of family hypertrophic cardiomyopathy which associated with apical hypertrophy and mild symptom.It is a reasonable procedure in HCM patients with apical hypertrophy and mild symptom to screen mutation in TNNI3 gene.

关 键 词：肥厚型心肌病 肌钙蛋白Ⅰ基因 基因突变 表型 

分 类 号：R542.2[医药卫生—心血管疾病]