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

• Published in: Russian journal of genetics 2024-06, Vol.60 (6), p.809-816
• Main Authors: Kiselev, I. S., Kozin, M. S., Baulina, N. M., Sharipova, M. B., Zotov, A. S., Stepanova, E. A., Kurilina, E. V., Abdullaeva, G. Zh, Zateyshchikov, D. A., Favorova, O. O., Chumakova, O. S.
• Format: Article
• Language: English
• Subjects: Animal Genetics and Genomics; Biomedical and Life Sciences; Biomedicine; Human Genetics; Microbial Genetics and Genomics
• ISSN: 1022-7954; 1608-3369
• DOI: 10.1134/S102279542470025X

— 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.