Targeted exome analysis of Russian patients with hypertrophic cardiomyopathy

Abstract

Background: Hypertrophic cardiomyopathy (HCM), described as the presence of hypertrophy of left ventricular, is the most prevalent heritable cardiovascular disease with predominantly an autosomal dominant type of inheritance.However, pathogenic alleles are not identified in at least 25% of patients with HCM, and the spectrum of pathogenic variants that contribute to the development of HCM in Russia has not been fully described. Therefore, the goal of our study was to identify genetic variants associated with the etiopathogenesis of HCM in Russian patients. Methods:The study cohort included 98 unrelated adult patients with HCM. We performed targeted exome sequencing, an analysis using various algorithms for prediction of the impact of variants on protein structure and the prediction of pathogenicity using ACMG Guidelines. Results:The frequency of pathogenic and likely pathogenic variants in all HCMrelated genes was 8% in our patients. We also identified 20 variants of uncertain significance in all HCM-related genes. Conclusions:The prevalence of individual pathogenic variants in HCM-related genes in Russian population appears to be lower than in general European population, which could be explained by ethnic features of Russian population, age characteristics of our sample, or unidentified pathogenic variants in genes previously not linked with HCM.

Hypertrophic Cardiomyopathy in Underrepresented Populations: Clinical and Genetic Landscape Based on a Russian Single-Center Cohort Study

“…The rate of ICD implantation was extremely low (5.7 vs. 12-26%) [23][24][25][26]28], and the rate of SCD was about two times higher compared to Western populations [23][24][25]. The same low rate of ICD use (1% at enrollment) was reported in another Russian cohort [29]. The rate of all-cause mortality in a cohort of Russian HCM patients (2.86% per year) was also higher compared to studies from the last decade, and only similar to the SHaRe registry (2.76% per year for the whole cohort) [24], which has been enrolling patients since 1960, when the ICD implantation was not used.…”

“…In Western countries, the prevalence of the p.Q1233* variant is less than 1% [24,26,34]. In the only cited genetic study in Russian HCM population [29], the p.Q1233* variant was identified in 2% of genotyped patients, but the overall yield of genetic testing was unexpectedly low, only 20%, and the prevalence of the p.Q1233* variant among the G+ patients was 10%. Our results make the MYBPC3 p.Q1233* variant a candidate for a founder effect confirmation study.…”