Clinical And Genetic Study On Primary Dilated Cardiomyopathy In Wenshan

Cardiomyopathy,a kind of heterogeneous heart disease,when severely can lead to progressive heart failure and cardiovascular death,usually divide into primary cardiomyopathy and secondary cardiomyopathy.Hereditary cardiomyopathy is a common cardiovascular disorder with a wide range of patients.The prevalence is about 0.9/1000,and the male is about twice than women.According to the shape of ventricular and energy supply,it can be divided into hypertrophic cardiomyopathy(HCM),dilated cardiomyopathy(DCM),restrictive cardiomyopathy(RCM)and arrhythmogenic right ventricular cardiomyopathy(ARVC).Dilated cardiomyopathy is a kind of primary cardiomyopathy,which characteristic by left ventricular or biventricular enlargement and systolic dysfunction,often occurs congestive heart failure,accounting for 70%-80% of cardiomyopathy.In addition to heart transplantation,there is currently no thorough treatment.The prevalence is approximately 1/2500,and about 48% of patients have family heredity,which mainly inherited by autosomal dominant inheritance.To date,at least 50 pathogenic genes have been found to be associated with DCM.Gene testing is the major method for detecting genetic diseases.Inherited cardiomyopathy has been associated with multiple gene mutions that could be sequenced by using conventional Sanger sequencing.However,this kind of method is time-consuming,laborious and expensive.Next-generation semiconductor sequencing technology(Ion torrent PGM)can simultaneously sequencing on multiple target genes,with the advantages of high throughput,fast and cheap,etc.,has become the best choice for small genome sequencing,genetic variation of multiple genes.As a result of genetic and environmental factors,and it has a significant ethnic difference.Inherited cardiomyopathy was widely prevalent in a variety of ethnic in Yunnan Province,the special geographical environment and climate.To our knowledge,this is the first systematic screening for patients with DCM in Yunnan;it is also necessary for the discussion between genetic and phenotype of DCM.This study is based on the ethnic minority patients with DCM in Wenshan,Han,Zhuang,Miao and Yi nationalities in Yunnan province.The purpose is to analyze the clinical features of DCM cases in Wenshan,and construct a sample library of DCM.Data base.Samples are collected from the Department of Cardiology of Wenshan Prefecture People's Hospital from November 2015 to May 2017 total of 660 cases,Through statistical comparison of clinical phenotypes among ethnic groups and people of all ages in different regions,it was found that dilated cardiomyopathy in Wenshan area is more common in men,the male-female ratio is about 2:1,and the incidence is more common in middle age.By comparing the clinical differences between left and right ventricular diameters and EF values in different genders,different ages,different ethnic groups and different regions,no statistically significant differences were found.Six families of 660 patients with a family history of DCM were subjected to high throughput sequencing.And the relationship of clinical features and genotypes were analyzed.Through mutation screening in patients with DCM,DSP-Tyr494 Phe,DSP-Gln1648 Arg,TNNT2-Lys263 Arg,MYH6-Ala1130 Thr,MYBPC3-Glu334 Lys,TTN-Thr2690 Ile and SCN5A-Arg1139 Gln of total 7 mutations were found to be hot mutations in Yunnan.There are three types,single-hybrid genetic mutation,two-hybrid genetic mutation and three-hybrid mutation in the family,and the double-hybrid mutation has a dose effect,which accelerates or aggravates the clinical phenotype.In addition,comparing the positive mutation group and the negative mutation group,the clinical phenotype of the positive mutation group was more severe than that of the negative,and the age of onset became more and more young.In summary,based on the next-generation semiconductor chip sequencing platform,this study established a high throughput mutation screening method for DCM,which was used to screen mutations in patients with DCM in Yunnan province.The molecular genetics confirms the high correlation between genotypes and clinical phenotypes.It provides first-hand information for hereditary cardiomyopathy's prevention and treatment in Yunnan area,and also provides a method for the detection of pathogenic genes in DCM.