Mutations in cardiac ion channel genes in hypertrophic cardiomyopathy
Abstract
Background. Hypertrophic cardiomyopathy (HCM) is a hereditary myocardial disease caused by mutations in sarcomere protein genes. The disease is characterized by a heterogeneous phenotype, variable intra- and inter-family expressivity and incomplete penetrance. Such disease variability may indicate the presence of other genetic factors, the so-called modifier genes, including genes encoding ion channel subunits associated with potentially lethal ventricular arrhythmias. The aim of the study was to search for mutations in sarcomere protein and cardiac ion channel genes in patients with HCM and to study clinical manifestations of the disease depending on the genotype.
Material and methods. The study included 78 unrelated Belarusian patients with a high risk of sudden cardiac death (SCD). Genotyping was performed using the TruSight Cardio Sequencing Kit (Illumina).
Results. Rare mutations in 5 ion channel genes were detected in 13 (16.7%) patients with HCM: KCNQ1 (4), KCNH2 (3), CACNA1C (4), SCN5A (1) and ANK2 (2): 28.6% mutations are pathogenic, 57.1% are VUS, 14.3% are new, pathogenic according to in silico predictors. Only 7 out 13 pa- tients had mutations in sarcomere genes (4 pathogenic and 3 VUS). It was shown that the presence of mutations in ion channel genes in patients with HCM in combination with changes in sarcomere protein genes contributes to the early disease manifestation and increased risk of SCD regardless of mutations in sarcomere protein genes.
Conclusion. The presence of mutations in ion channel genes in patients with HCM can increase a risk of life-threatening arrhythmias and SCD development and influence their prognosis and treatment.
Keywords:hypertrophic cardiomyopathy, mutations, sarcomere protein genes, cardiac channelopathies, cardiac ion channel genes, next generation sequencing (NGS), phenotypic features
For citation: Chakova N.N., Komissarova S.M., Niyazova S.S. Mutations in cardiac ion channel genes in hypertrophic cardiomyopathy. Clin Experiment Surg. Petrovsky J. 2019; 7 (3): 63–9. doi: 10.24411/2308-1198-2019-13007 (in Russian)
Received 15.06.2019. Accepted 25.07.2019.
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