Complete sequencing of sarcomere genes in hypertrophic cardiomyopathy patients identified mutations in 40%, most commonly in MYBPC3 (54.5%) and MYH7 (31.8%).
Observational (n=100)
What is the frequency and spectrum of mutations in MYH7, MYBPC3, TNNI3, and TNNT2 genes in Central European patients with hypertrophic cardiomyopathy?
In a Central European HCM cohort, MYBPC3 was the most commonly mutated gene, and the high phenotypic heterogeneity and novel mutations suggest targeted pre-screening tests are ineffective.
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.
Čurila et al. (Wed,) conducted a observational in Hypertrophic cardiomyopathy (n=100). Complete sequencing of MYH7, MYBPC3, TNNI3 and TNNT2 genes was evaluated on Presence of mutations in MYH7, MYBPC3, TNNI3 and TNNT2 genes. Complete sequencing of sarcomere genes in hypertrophic cardiomyopathy patients identified mutations in 40%, most commonly in MYBPC3 (54.5%) and MYH7 (31.8%).
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