The Pathogenic Gene Screening In A Hypertrophic Cardiomyopathy Family In Yunnan And The Relationship Between Genotypic And Phenotypic

Objective:Hypertrophic cardiomyopathy(HCM)is a clinically common type of cardiomyopathy.With the development of molecular genetics technology,the role of genetic factors in the pathogenesis of HCM has gained a profound recognition among the world of medicine,and the familial hypertrophic cardiomyopathy(FHCM)with family clustering has also received increasing attention.Current research shows that the genetic mutations of at least 25 genes and more than 1500 gene-locus have been related to HCM.This study,we investigate the relationship between genotype and phenotype of a cardiomyopathy pedigree by screening the candidate pathogenic genes of family members with HCM,which will further enrich the domestic spectrum of mutations in the genes of familial cardiomyopathy.As well as provides an important theoretical basis for mechanism of molecular genetic research,early screening and early intervention treatment of familial hypertrophic cardiomyopathy.Methods:1.Participants:A total of 15 members among the HCM proband and other family members from Yuxi City,Yunnan Province.This study was approved by the Ethical Committee of Yuxi People's Hospital of Yunnan Province.Both the proband and other family members had signed the informed consent.2.General clinical data collection:detailed history and family history collection,physical examination,conventional 12-lead electrocardiogram and echocardiography examination were performed among the family members.According to the collected family data,the pedigree genetic map was drawn,and analyzed the pedigree genetic characteristics and clinical phenotypes.3,Gene analysis:Collected peripheral venous blood samples of the proband and other family members,checked the latest literature to find out all the FHCM pathogenic genes which were identified currently as candidate genes,and then sent the venous blood sample of the proband to the Jinyu gene testing company,where the high-throughput sequencing of the exon target region captures were taken,so as to screen the exon target regions and mutant sites of the candidate genes.After obtaining the suspicious mutations,Sanger sequencing was used to verify whether there were suspicious mutations in other family members.Results:The high-throughput sequencing and Sanger sequencing of the candidate gene exon of this family revealed the fact that GLA c.167G>A(p.Cys56Tyr)heterozygous or hemizygous missense mutation,ZFPM2 c.1332G>C(p.Lys444Asn)heterozygous missense mutation,SCN5A c.5216G>A(p.Arg1739Gln)heterozygous missense mutations and the translated amino acids were changed.The GLA gene mutation was X-linked inheritance,ZFPM2 mutation was autosomal dominant inheritance,and SCN5A caused autosomal dominant or recessive inheritance.HCM patients were found in the two generations of the family,and most of the members of the third generation of family members born with kinship were attacked.They all carried heterozygous or hemizygous mutations of the GLA gene.Conclusions:X-linked inheritance is the main genetic mode of HCM in this family.GLAc.167G>A(p.Cys56Tyr)heterozygous or hemizygous missense mutation may be the major pathogenic mutation in this family of hypertrophic non-obstructive cardiomyopathy.