Clinical Study On Pathogenic Gene Of Familial Hypertrophic Cardiomyopathy

Backgrounds Hypertrophic cardiomyopathy(HCM)is the most common inherited cardiac disease with significant genetic heterogeneity.HCM has been recognized for more than 50 years,recently substantial advances in diagnosis and treatment options have been achieved,as well as increased recognition of the disease in clinical practice.At present,more than 1,500 mutations in 27 genes have been found to be associated with HCM.The study of HCM pathogenic genes in China is usually limited to several genes that encode the sarcomere,which inevitably leads to the decrease of the detection rate of pathogenic genes,so that a number of HCM cases can not be found with pathogenic genes,not alone the screen of its family members and genetic studies.Objective New generation of high-throughput sequencing technology(NGS)was used to sequence the 44 genes of the target genomes associated with human cardiomyopathy,and the characteristics of gene mutation and the relationship between genotype and clinical phenotype were analyzed.Methods From 2012 to 2016,15 probands of familial hypertrophic cardiomyopathy(FHCM)were enrolled in the Chest Hospital of Henan Province.Clinical datas were collected(including medical history,physical examination,heart color Doppler ultrasound,electrocardiogram)and a total of 44 genes associated with cardiomyopathy were screened.For the probands of positive genotype,the specific genes of other members in the family were detected by Sanger sequencing.The pathogenicity of the newly discovered mutant gene was determined by comparing the protein sequence homology of different species,and compared with the healthy control group.Finally,the genotype and phenotypic correlation of pathogenic mutant carriers were analyzed.Results Of the 15 probands with hypertrophic cardiomyopathy,nine mutations were identified in the 8 probands with 5 related pathogenic genes,including 1 cases of double gene mutation,and 2 cases of new mutations which have not been reported at home and abroad.Conclusion 1.c.2834G>A in MYBPC3 gene and c.903 del G in MYBPC3 gene mutations have not been reported at home and abroad,which are newly discovered pathogenic mutations.Phenotype of c.903 del G mutation in MYBPC3 gene is serious,prone to malignant heart rate disorders,and the treatment needs to be taken more active measures.Phenotype of c.903 del G mutation in MYBPC3 gene is diverse.2.A de novo mutation can happen on the basis of inheritance.Digenic mutations presented with a younger onset age,more serious myocardial hypertrophy,severe symptoms and poor clinical outcome.