Preliminary exploration of genotype-phenotype correlation in chinese with hypertrophic cardiomyopathy

Abstract

Objective To explore the genetic mutation spectrum of patients with hypertrophic cardiomyopathy(HCM) and analysis the correlation of genotype phenotype. Methods Collect peripheral venous blood of the 51 cases unrelated HCM patients(35 male and 16 female) in the Beijing Anzhen Hospital of Capital Medical University from 2013 to 2016. Sequence whole exons of human and analysis seven major mutations of HCM including: MYBPC3、MYH7、TNNT2、TNNI3、MYL2、TPM1 and ACTC1. Then compare the results with clinical characteristics. Results 24 patients(47.1%) had 22 kinds of pathogenicity or possibly pathogenicity mutations. The 90.9%(20/22) of mutations only occurred one time, except MYH7 gene’ s 663 amino acid and the TNNI3 gene’s 157 amino acid which had twice. The mutations of MYBPC3, MYH7, TNNT2, TNNI3, MYL2, TPM1 and ACTC1 accounted for 45.8%(11/24), 20.8%(5/24), 12.5%(3/24), 8.3%(2/24), 8.3%(2/24), 4.2%(1/24), and 0 respectively. No amphimutation had been found that causes illness or possibly. Through the comparison of clinical features between Genotype positive(24 cases) and negative(27 cases) patients: the incidence of syncope(19.6% vs. 7.8%, P<0.05), the largest left ventricular wall thickness[(22.8±2.6)mm vs.(20.0±3.4)mm, P<0.05], family history of HCM(20.8% vs. 0, P<0.05), percentage of apical hypertrophy(25.5% vs. 11.8%, P<0.05); The ratio of left ventricular outflow tract obstruction in MYH7 group was higher than MYBPC3 group(80.0% vs. 18.2%, P<0.05). Conclusion MYBPC3 is the most common mutation gene in HCM patients. Phenotype is more severe in genotype positive patients than in genotype negative patients. Relationship between specific gene mutations and clinical phenotype requires further study. Key words: Hypertrophic cardiomyopathy; Genotype; Phenotype; Genetic; Pathogenicity