肥厚型心肌病肌钙蛋白T基因突变的研究

目的调查中国人群肥厚型心肌病(HCM)患者基因突变的发生情况并对基因型与临床表型之间的关系进行分析。方法对71例HCM先证者及100名正常对照的聚合酶链反应扩增产物行单链构象多态性分析,于肌钙蛋白T(TNNT2)基因第8、9、10、11、16外显子范围内寻找突变位点,并了解基因型明确的HCM患者的临床特点。结果 在1例患者TNNT2基因的第9外显子上发现了一个新的错义突变位点124A>C(K124N)。由于在100名正常对照中未见该错义突变,故我们认为此突变位点为该患者的致病基因位点。该患者38岁起出现临床症状,超声表现为室间隔中度肥厚,家族中无心源性猝死发作史。结论肌钙蛋白T的尾端对于其连接功能起着至关重要的作用,该区域的基因突变可导致肥厚型心肌病的发生。证实了该病具有异质性遗传的特点。

A novel missense mutation, K124N, in the troponin T gene of Chinese populations with hypertrophic cardiomyopathy

OBJECTIVE: To study the cardiac troponin T (TNNT2) gene mutation in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the correlation between the genotype and phenotype. METHODS: Specimens of peripheral blood were collected from 71 unrelated Chinese probands with HCM, aged 40 +/- 18. The genome DNA was extracted. Single-strand conformation polymorphism gel analysis of the polymerase chain reaction-amplified products was conducted to search for mutations in the exons 8, 9, 10, 11, and 16 of the TNNT2 gene. Relevant clinical data were collected. One hundred normal persons, aged 44 +/- 14, were used as controls. RESULTS: A missense mutation, K124N, in the exon 9 of the TNNT2 gene was identified in a 41-year-old female patient with HCM and failed to be detected in the 100 normal controls, which suggested the disease-causing mutation. The patient began to have the symptoms of chest distress and palpitation since the age of 38, presented moderate hypertrophy of the intraventricular septum, and did not have a family history of sudden cardiac death. CONCLUSION: A novel missense mutation of troponin T gene has been identified. Mutation in tail part of cardiac troponin T, essential for it's binding function, causes the disease of HCM. Correlative analysis confirms the genetic heterogeneity of the disease.