肥厚型心肌病患者心脏肌钙蛋白T基因变异及其相关临床表型分析

Novel mutations of cardiac troponin T in Chinese patients with hypertrophic cardiomyopathy

目的探讨中国人群肥厚型心肌病（HCM）患者中心脏肌钙蛋白T（cardiactroponin T，TNNT12）基因变异的情况，并分析基因型与临床表型的关系。方法对100例确诊为HCM的患者及部分家属进行临床评估分析并随访，聚合酶链反应扩增所有编码序列及内含子-外显子拼接部位，直接测序法分析TNNT2基因多态／突变情况。结果在100例先证者中发现1例R92W错义突变，1例R286H错义突变，突变率2％。发现3号内含子与4号外显子拼接部位5bpCYTCT序列的缺失／插入基因多态性改变，22例缺失缺失型（DD型）患者的临床特点与其余78例无显著性差异。结论在100例HCM患者中发现TNNT2基因2个错义突变-R92w和R286H，TNNT2突变在中国HCM患者中发生率较低。

Objective To screen the cardiac troponin T （TNNT2） mutations in Chinese patients with hypertrophic cardiomyopathy （HCM） and to analyze the potential link between the genotype and the phenotype. Methods Clinical features of 100 probands with HCM and some family members were evaluated, 200 unrelated normal subjects served as control. The exons and flanking introns of TNNT2 were amplified with PCR and direct sequencing was used to screen TNNT2 mutations/ polymorphisms. Results Two novel missense mutations were detected in 2 HCM patients： R92W and R286H. These 2 mutations were not found in 200 non-HCM controls. A five-basepair insertion/deletion polymorphism in intron 3 of TNNT2 was identified in this HCM cohort but was not related to the phenotype. Conclusions Two missense mutations, R92W and R286H, were found in 2/100 patients with HCM, TNNT 2 mutation is relatively low in Chinese patients with HCM.