Research On Disease-causing Gene Mutations In Chinese Patients With Hypertrophic Cardiomyopathy

Objective: To study the disease-causing gene mutations in Chinese with familial hypertrophic cardiomyopathy(FHCM),summarize the characteristics of phenotype,and to analyze the correlation between the genotype and phenotype.Method: Specimens of thirteen unrelated Chinese families with HCM were chosen for the study,extract DNA from their peripheral blood.Single-strand conformation polymorphism gel analysis of the polymerase chain reaction-amplified products was conducted to search for mutations in the exons 3-27 of the β-myosin heavy chain gene(MYH7),in the exons 2-35 of the cardiac myosin-binding protein C gene(MYBPC3),in the exons 2-16 of the cardiac troponin T gene and in the exons 3、5、7、8 of the cardiac troponin I gene(TNNI3).The PCR products of the thirteen Chinese pedigrees with HCM and 100 age-matched normal control subjects were sequenced. Results of DNA sequenced were analyzed and mutation sites were determined.The genotype data of these families were collected and the correlation between the genotype and phenotype was analyzed.Result: Two new mutations found in MYH7 gene in 2 out of 13 pedigrees were Arg1114Cys、Glu1142Lys mutations in exon 26.The two mutations were cosegregate with the disease,and were firstly identified at home and abroad, while the results of genetic test were normal in one hundred controls.Arg143 Gln mutation in MYH7 and Ala157 Val mutation in TNNI3 gene which had been reported were found in 2 pedigrees,the phenotype characteristics of the 2 pedigrees was consistent to the data reported previously.Ser236 Gly mutation in MYBPC3 gene was found in 3 probands,which had been reported abroad and regarded as a kind of polymorphism.Besides,several same sense mutations were found.Conclusion:Two new mutations were found in 2 out of 13 pedigrees.The pedigree carried Arg1114Cys mutation had a low rate of penetrance、mild symptoms、a slow英文摘要中国汉族家族性肥厚型心肌病致病基因的突变研究progress and a good survival prognosis.The pedigree carried Glu1142Lys mutation had a severe degree of myocardial hypertrophy and a high risk of sudden death,had an unfavorable prognosis.