The Novel Frameshift Variant of the MYBPC3 Gene Associated with Hypertrophic Cardiomyopathy Significantly Decreases the Level of This Gene Transcript in the Myocardium

IF 0.6 4区生物学 Q4 GENETICS & HEREDITY Russian Journal of Genetics Pub Date : 2024-06-19 DOI:10.1134/s102279542470025x

I. S. Kiselev, M. S. Kozin, N. M. Baulina, M. B. Sharipova, A. S. Zotov, E. A. Stepanova, E. V. Kurilina, G. Zh. Abdullaeva, D. A. Zateyshchikov, O. O. Favorova, O. S. Chumakova

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Abstract—

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease with a prevalence of 1 : 200–1 : 500 in the general population. Most HCM-linked pathogenic (or likely pathogenic) variants are located in eight genes encoding proteins of sarcomere, the main contractile unit of cardiomyocytes, primarily in MYBPC3; MYBPC3 variants are usually associated with a relatively benign clinical course of the disease. Here, we describe a novel frameshift heterozygous variant NM_000256.3:c.2781_2782insCACA of the MYBPC3 gene, which causes familial HCM. The proband had a progressive heart failure despite the surgical removal of left ventricular tract obstruction. Evaluation of levels of transcripts produced from the mutant allele and wild-type allele of the MYBPC3 gene in proband myocardial tissue and comparison of their total levels with those in the control samples from patients without HCM showed a significant allele-specific reduction of mutant transcript levels. Our results expand the spectrum of known genetic variants with a proven role in the development of HCM.

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与肥厚型心肌病有关的新型 MYBPC3 基因帧移位变异会显著降低该基因在心肌中的转录水平

摘要-肥厚型心肌病（HCM）是最常见的遗传性心脏病，在普通人群中的发病率为 1:200-1:500。大多数与 HCM 相关的致病（或可能致病）变异位于编码心肌细胞主要收缩单位--肌节蛋白的 8 个基因中，主要是 MYBPC3；MYBPC3 变异通常与该病相对良性的临床过程相关。在这里，我们描述了一种新型框架移位杂合变异 NM_000256.3:c.2781_2782insCACA，该变异可导致家族性 HCM。尽管通过手术切除了左心室道梗阻，但该患者仍出现了进行性心力衰竭。通过评估 proband 心肌组织中 MYBPC3 基因突变等位基因和野生型等位基因产生的转录本水平，并将其总水平与无 HCM 患者对照样本中的水平进行比较，结果显示突变转录本水平的等位基因特异性显著降低。我们的研究结果扩大了已知基因变异的范围，这些基因变异已被证实在 HCM 的发病中发挥作用。

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来源期刊

Russian Journal of Genetics 生物-遗传学

CiteScore

1.00

自引率

33.30%

发文量

126

审稿时长

1 months

期刊介绍： Russian Journal of Genetics is a journal intended to make significant contribution to the development of genetics. The journal publishes reviews and experimental papers in the areas of theoretical and applied genetics. It presents fundamental research on genetic processes at molecular, cell, organism, and population levels, including problems of the conservation and rational management of genetic resources and the functional genomics, evolutionary genomics and medical genetics.