Abstract

Hypertrophic cardiomyopathy (HCM) is considered the most common inherited heart disease. HCM is a highly heterogeneous disease from the genetic point of view. However, the cause of the disease remains unclear, despite the large number of pathogenic variants detected in more than a quarter of patients. Therefore, studying the prevalence of pathogenic variants associated with HCM especially in the Russian population is still relevant. In this context, the objective of the research survey was to assess the contribution of pathogenic variants rs200411226 and rs397515905 in the MYBPC3 gene, leading to substitutions R495Q, R495W, and R495G, to the development of HCM in the Russian population. The sample included 224 patients with HCM of varying severity. The genotypes of variants rs200411226 (NM_000256.3:c.1484G>A) and rs397515905 (NM_000256.3:c.1483C>T/G)) in the MYBPC3 gene (R495Q, R495W, and R495G) were analyzed for all the patients with real-time PCR. The survey analysis of the prevalence of these pathogenic variants has shown that the R495Q and R495W mutations in the survey sample occur with a frequency of 0.4% for each mutation, which is generally comparable with the frequencies of these pathogenic variants in the other populations. In addition, R495Q and R495W mutations do not appear to cause a severe form of the disease. Survey testing failed to identify the R495G pathogenic variant in the survey sample of HCM patients. Therefore, these mutations themselves as a cause for HCM progression do not have any significant prevalence among the Russian population.

中文翻译：

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俄罗斯肥厚型心肌病患者 MYBPC3 基因突变的患病率

摘要

肥厚性心肌病 (HCM) 被认为是最常见的遗传性心脏病。从遗传的角度来看，HCM 是一种高度异质性的疾病。然而，尽管在超过四分之一的患者中检测到大量致病变异，但该病的病因仍不清楚。因此，研究与 HCM 相关的致病变异的流行率，尤其是在俄罗斯人群中仍然具有相关性。在这种情况下，研究调查的目的是评估致病变异 rs200411226 和 rs397515905 在 MYBPC3 中的作用基因，导致替代 R495Q、R495W 和 R495G，导致俄罗斯人群中 HCM 的发展。样本包括 224 名不同严重程度的 HCM 患者。MYBPC3中变异rs200411226 (NM_000256.3:c.1484G>A)和rs397515905 (NM_000256.3:c.1483C>T/G))的基因型使用实时 PCR 分析所有患者的基因（R495Q、R495W 和 R495G）。对这些致病变异流行率的调查分析表明，调查样本中的 R495Q 和 R495W 突变发生频率为每个突变的 0.4%，这与这些致病变异在其他人群中的频率大体相当。此外，R495Q 和 R495W 突变似乎不会引起严重的疾病。调查测试未能在 HCM 患者的调查样本中识别出 R495G 致病性变异。因此，这些突变本身作为 HCM 进展的原因在俄罗斯人群中没有任何显着流行。