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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 causative genes of Chinese hypertrophic cardiomyopathy (HCM) and analyze the relationship between genotypes and clinical phenotypes. Methods The mutations of cardiac troponin T gene (TNNT2), cardiac myosin binding protein C (MYBPC3) and MYH7 were screened in a HCM pedigree. The polymerase chain The exon fragment of its functional region was amplified by PCR and sequenced by dideoxy terminator method. Pedigree survey data included clinical manifestations, physical examination, echocardiography and cardiogram. RESULTS: Of the 10 subjects who underwent pedigree in this pedigree, 4 had TNNT2 14035c> t (R130C) mutations, all of which developed before the age of 40 with a penetrance of 100%. The normal control group in the same location without exception, the mutation site of TNNT2 gene exon 130 of arginine into cysteine, proband and his two brothers are mainly manifested in cardiac dysfunction, The two elders of the proband died of sudden death during our follow-up. No mutations were found in MYH7 and MYBPC3 genes. Conclusion The 14035c> t mutation of TNNT2 gene is a causative mutation in this HCM pedigree. The carrier’s clinical phenotype more evil. More malignant clinical phenotype, a higher incidence of sudden death HCM family is necessary for TNNT2 mutation screening.