Abstract

Mutations in the MYBPC3 gene are currently believed to lead to the development of hypertrophic cardiomyopathy (HCM) in the majority of genetically determined cases. However, despite many years of research, both in worldwide and in Russia in particular, the genetic landscape of HCM is still insufficiently studied. Moreover, the insufficient study of genetically determined cases of HCM in the Russian population does not allow us to study the possible relation of the phenotypic characteristics of HCM patients with certain pathogenic variants of the genome of these patients. In this regard, the purpose of our work was to study the prevalence of rare pathogenic variants rs730880711 and rs397515974 of the MYBPC3 gene in HCM patients from Russia and to assess the effect of these mutations on the severity of this disease. The sample included 180 patients with moderate HCM and 137 patients with severe HCM. Analysis of the genotypes of rs730880711 (NC_000011.10:g.47342928_47342929insG; V453X) and rs397515974 (NC_000011.10:g.47337452G>C; Y847X) variants in the MYBPC3 gene was carried out in genomic DNA samples isolated from peripheral blood by real-time PCR. The performed analysis of the prevalence of rare pathogenic variants rs730880711 and rs397515974 in the MYBPC3 gene in patients with moderate and severe forms of HCM from Russia showed that the frequency of each mutation was 0.003. Both pathogenic variants were identified in individuals with the moderate disease. Thus, the indicated mutations are extremely rare in HCM patients from Russia and do not make a significant contribution to the development of this disease in the Russian population.

中文翻译：

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MYBPC3 基因中的罕见突变 V453X 和 Y847X 不会导致俄罗斯人群出现严重的肥厚性心肌病

摘要

目前认为，在大多数由基因决定的病例中，MYBPC3基因突变会导致肥厚型心肌病 (HCM) 的发生。然而，尽管在世界范围内、特别是在俄罗斯进行了多年的研究，但 HCM 的遗传景观仍然没有得到充分研究。此外，对俄罗斯人群中基因决定的 HCM 病例的研究不充分，不允许我们研究 HCM 患者的表型特征与这些患者基因组的某些致病性变异之间的可能关系。在这方面，我们工作的目的是研究俄罗斯 HCM 患者中MYBPC3基因的罕见致病性变异 rs730880711 和 rs397515974 的患病率，并评估这些突变对该疾病严重程度的影响。样本包括 180 名中度 HCM 患者和 137 名重度 HCM 患者。在从外周血分离的基因组 DNA 样本中对MYBPC3基因中的 rs730880711 (NC_000011.10:g.47342928_47342929insG; V453X) 和 rs397515974 (NC_000011.10:g.47337452G>C; Y847X) 变体的基因型进行分析真实的血时PCR。对俄罗斯中度和重度 HCM 患者MYBPC3基因中罕见致病性变异 rs730880711 和 rs397515974 的患病率进行的分析表明，每种突变的频率均为 0.003。在患有中度疾病的个体中发现了这两种致病变异。因此，所指出的突变在俄罗斯 HCM 患者中极为罕见，并且不会对俄罗斯人群中这种疾病的发展做出重大贡献。