Analysis Of 18 And 20 Exons Mutation In MYH7 Gene With Sporadic And Familial Hypertrophic Cardiomyopathy In Anhui At Some Areas

Background:Hypertrophic cardiomyopathy(HCM) is a genetic disordertypically inherited in an autosomal dominant model,which is also showed chromosome recessive inheritance,X-chromosome links in somecases.About 50 percent of HCM patients exhibit an obvious familial aggregation.Besides,its high penetrance rises up with ages.Correlative studies demonstrated that HCM presented in 0.2%of general population.So,HCM is the most common genetic heart disease.In China,the recent two reports showed the disease phenotype for hypertrophic cardiomyopathy was identified in 0.16%of subjects and the annual mortality rate was 1.6%or so.Clinical manifestations involve ventricular hypertrophy,especially ventricular septum asymmetric hypertrophy,cardiac arrhythmia,exercise intolerance and sudden death.Generally encoded cardiac sarcomere genes mutations are molecular mechanisms of HCM.About 14 encoding cardiac sarcomere genes whose mutations caused HCM have already been found.But three of the HCM-caused mutant gene predominated in frequency:β-myosin heavy chain gene(MYH7),cardiac myosin-binding protein C gene(MYBPC3) and troponin T gene(TNNT2).β-myosin heave chain(MYH7) is the major element of sarcomere.Thirty to fifty percent of HCM resulted from mutations ofβ-MHC gene.In China,the reported rate is 41 percent.MYH7gene located on chromosome 14q11.2-q13(length:23 kb),the gene consists of 40 exons and 38 of which encoding 1935 amino acids whereas its mRNA is 3 kb. Most of mutations take place on exon 3 to 26.By far,more than 80 SNPs have been found to cause the amino acid changes in the two regions:global head and head-rod junction of MYH7.At the same time,Some researches showed sporadic hypertrophic cardiomyopathy(SHCM) may be existed the similar pathogenesis as that of FHCM.Objective:This study was designed to analyze the mutation of the beta myosin heavy chain gene(MYH7) between patients with familial and sporadic hypertrophic cardiomyopathy in Anhui provience.Methods:In this study,smples of peripheral blood were collected from eight patients with familial HCM(FHCM) and 20 patients with sporadic hypertrophic cardiomyopathy(SHCM) from different areas of Anhui province.The 3-26 protein-coding exons in the functional regions of MYH7 were amplified with PCR and the products were sequenced.Results:Five HCMs the 8 FHCM patients harbored two different mutations in MYH7 gene,Arg723Gly in exon 20 and Arg663His in exon 18;one of the 20 SHCM patients harbored 1 mutation in MYH7 gene,Ile736Thr in exon 20.Conclusions:Exon 20 and 18 may be the frequent disease-causing exons in MYH7 gene in FHCM of Anhui area;SHCM may share the similar pathogenesis as that of FHCM,however,the mutation rate of MYH7 gene is significantly lower than HCM.