| Background:Hypertrophic Cardiomyopathy (HCM) is the most frequent cause of sudden cardiac death (SCD) in young people (include athletes) and the identification of high-risk patients is still a challenge for doctors and researchers. The conventional risk stratification algorithm has so many limitations. The development of biotechnology in recent years makes the gene screening become an important tool for disease risk assessment and family screening.Method:19SCD patients with hypertrophic cardiomyopathy were included in this study. Genomic DNA was extracted from peripheral blood leukocytes. Twenty-six HCM-related genes were comprehensively screened for mutations with targeted resequencing (Next Generation Sequencing). The identified mutations were confirmed with bi-directional Sanger sequencing (Chain Termination Method). All the people were subjected to a full clinical evaluation. Analyze the relationship between genotype and phenotype, assess the correlation of genotype and SCD.Results:The average age of patients suffered SCD was48.7±19.0years old. SCD can happen at all stages of the patients’life. The youngest only11years old and the eldest was84years old. According to the gene testing, we identified6patients with two mutations,6patients with single mutation and7patients with no mutation. We found18mutations (17types) located in four genes included MYBPC3(8), MYH7(6), MYL2(2) and TNNI3(2). Multiple mutations carriers accounted for31.6%.12types were new mutations and5types were previously reported. The phenotype of these5types was different from reported cases, even if they had the same genetic mutation. The more mutations the patients carried, the younger of the age at onset (p=0.015) and SCD (p=0.009).Conclusion:Our results suggest that:(1) these mutations we find may be the "malignant" mutations which can caused SCD;(2) multiple mutations in patients is a risk factor for SCD;(3) HCM has a strong genetic heterogeneity and phenotypic heterogeneity. |
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