Mutation spectrum in MYBPC3 gene in patients with hypertrophic cardiomyopathy

Abstract

Introduction. Hypertrophic cardiomyopathy is one of the most frequent monogenic cardiovascular diseases. However, diagnosis of primary HCM is very challenging due to many causes of secondary hypertrophy. Genetic causes of HCM are also quite diverse - after screening of all causative genes known, mutations can be identified in 60% of familial cases. The aim of this study was to investigate mutation spectrum of MYBPC3 gene in the group of patients with myocardium hypertrophy. Material and methods. DNA samples of 77 patients with myocardium hypertrophy were collected. Mutation screening was performed by Sander sequencing of MYBPC3 gene or by semiconductor sequencing of MYBPC3 gene as a part of gene panel on Ion Torrent platform followed by confirmation of detected variants by Sanger sequencing. Results and discussion. In MYBPC3 gene 6 mutations were detected in 10 unrelated families. Also 4 variants of unknown clinical significance were found and 2 frequent coding polymorphisms. Nonsense mutation p.Q1233* was found in 5 unrelated families (6.5% of cases). Conclusion. Mutations in MYBPC3 gene were detected in 10 unrelated probands. Relatively low frequency of MYBPC3 mutations can be due to clinical heterogeneity of myocardium hypertrophy. Nevertheless, screening of gene panels is appears to be more promising in HCM patients, than partial sequencing of genes involved.