Analysis Of MYH7 Gene Mutation With Familial Hypertrophic Cardiomyopathy In Anhui

Background:Hypertrophic cardiomyopathy(HCM) is inherited as a Mendelian autosomal dominant trait;about 55%HCM patients have familial history.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.At present,15 encoding cardiac sarcomere genes which mutations caused HCM have already been found.MYH7 gene mutations account for 30%-50%.There are more than 1 million patients with hypertrophic cardiomyopathy(HCM) in China. But the distribution of site mutation of FHC gene in domestic is unknown.This research selected MYH7 to be candidate gene.Three HCM families were subjected for the study.Through proband genome DNA to be sequenced Directly,we would knowledge FHC mutations and the correlation between genotype and phenotype.in Anhui.Objective:The purpose of the study is to scan the disease-causing gene mutations of MYH7 gene patients with FHC in AnHui and to knowledge mutation site distribution of MYH7 gene.The correlation between genotype and phenotype is also analyzed.Methods:Three unrelated HCM families of han race and five normal controls came from Anhui province were enrolled in this study.The normal controls involved 3 males and 2 females,with age ranged from 42 to 66 years.Three scattered HCM patients3 males,0 females,aged 42 to 51 years,All subject were examined by echocardiography and electrocardiography(ECG).Clinical data included physical examination,ECG,two-dimensional echocardiography and Doppler echocardiography. ventricular septum or ventricular wall thickness≥15 mm,absence of another cardiac or systemic disease.FHC patients were defined,as there were at least two patients in the same family.No abnormality was seen with respect to physical examination.The exon in the functional regions of the MYH7 gene were amplified with PCR and the products were sequenced.The relation between the genotype and phenotype was analyzed.Results:Three families probands have the MYH7 gene missense mutation. Sequencing results diplayed:the nt2013 C reduce and nt2025 C insert in mutation were identified in exonl 8 of MYH7 gene in one pedigree.The controls were normal in the genetic test.Conclusions:This study had confirmed 1 mutations of MYH7 gene among 3 FHC families.MYH7 accounts for 30%.It was identical to foreign reports.The other families had not been found any disease-cause mutation of MYH7.It reflected that HCM have genetic heterogeneity.In this study,the nt2013 C reduce and nt2025 C insert in mutation that identified firstly in Chinese.MYH7 mutations were associated with HCM in the FHC patients of Anhui province.In one family,the identical mutation has different phenotypes and prognoses,and identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of FHC.