The Pathogenic Gene Screening In A Cardiomyopathy Pedigree Of Yunnan Province And Relationship Between Genotype And Phenotype

Objective:Dilated Cardiomyopathy(DCM) and Hypertrophic Cardiomyopathy (HCM)are main types of cardiomyopathies.With the development of molecular genetics technology, the role of genetic factors in the pathogenesis of DCM and HCM are gettingmore and more attention with the presence of familial DCM and HCM.More than 40 pathogenic genes of familial DCM and 20 familial HCM virulence genes have been identified, some of which are shared in both cardiomyopathies, however, it has not reported that DCM coexists with HCM in the same familyinYunnan. In this study, we investigate the relationship between genotype and phenotype of a cardiomyopathy pedigree by sreening the candidate pathogenic genes of family memberswithcoexistence of DCM and HCM, which will further enrich the domestic spectrum of mutations in the genes of familial cardiomyopathy.As well as provides importanttheoretical basis for mechanism of molecular genetics research, early screening, early intervention treatment of familial DCM and familial HCM.Methods:1. A detailed history taking, physical examination, laboratory examination, ECG, and echocardiogram of the proband and other family members Were performed after informed consent. The 215 individuals with normal ECGs and echocardiograms were also included as healthy controls. According to the clinical data collected from the family, The genetic map was drawn, analysis of genetic characteristics and clinical phenotype.2. Peripheral Venous blood samples of probands and family members were collected.According to the latest literature, making all of the pathogenic gene of familial DCM and HCM which have now been identified as candidate gene, The venous blood samples of probands was send to Huada gene testing company for candidate gene exon high-throughput sequencing sub target capture, ultimately screening the target area of The exon and mutations of candidate genes TTN, TAZ and MYH7 were targeted using the candidate gene exon high-throughput sequencing sub target capture, and bidirectional sequencing of Sanger was conducted in other family members and controlgroups to testify the mutation of MYH7, TTN, TAZ.Results:The pedigree gave priority to autosomal dominant transmission with x-linked recessive transmission. Thefamily members carried TTN, TAZ, MYH7 missense mutation, which are predicted to change normal amino acid. No missense mutation of TTN, TAZ, MYH7 was found in control group.Conclusion:Autosomal dominant transmission is the main inheritance of HCM in the pedigree. Heterozygous missense mutation of MYH7c.730 T>C (p.Phe244Leu) is the main pathogenic mutation of non-obstructive HCM in this family, missense mutation of TAZ c.580A>G (p.Ile194Val) might be a novel pathogenic mutation, and TTN missense mutation may play a role of genetic modifier. The united effect of MYH7+/TTN+ or TAZ+/TTN+ heterozygous missense mutation might be associated with the early onset and severe phenotype.