Spectrum and clinical manifestations of mutations in genes responsible for hypertrophic cardiomyopathy

Introduction Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with autosomal dominant inheritance. It is caused by mutations in the genes coding for structural and/or regulatory proteins found in the sarcomere of cardiomyocytes. A group of genes, including the heavy chain of beta-myosin (MYH7), myosin binding protein C (MYBPC3), cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) are frequently affected by causal mutations. While exact mutation frequency data has been obtained for various populations, no screening has been reported for Central European populations. Patients and methods We performed a complete sequencing of MYH7, MYBPC3,TNNI3 and TNNT2 genes in 100 HCM patients. Results We discovered mutations in a total of 40 patients (40%), including 4 patients with double mutations. A total of 35 different mutation types were detected, of which 17 were novel. The contributions from individual genes were: 24 mutations in MYBPC3 (54.5%), 14 in MYH7 (31.8%), 4 in TNNI3 (9%) and 2 mutations in TNNT2 (4.5%). We have observed a wide variability in disease manifestation across the different genes/mutation types. In addition, we have discovered differences in both frequency and distribution of mutations of the two most common genes (MYBPC3 and MYH7) compared to other populations. Conclusion The most common gene responsible for HCM in our study population was MYBPC3, followed by MYH7,TNNI3 and TNNT2. Phenotypic heterogeneity, as well as the dissimilarity to other populations, prevents effective use of a pre-screening test, which would be directed at the most common mutation hotspots, in our population.