IMR Press / FBS / Volume 16 / Issue 1 / DOI: 10.31083/j.fbs1601001
Open Access Original Research
A New Leu714Arg Variant in the Converter Domain of MYH7 is Associated with a Severe Form of Familial Hypertrophic Cardiomyopathy
Show Less
1 Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050 Tomsk, Russia
2 Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050 Tomsk, Russia
3 Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia
*Correspondence: (Maria V. Golubenko)
Front. Biosci. (Schol Ed) 2024, 16(1), 1;
Submitted: 1 October 2023 | Revised: 15 January 2024 | Accepted: 29 January 2024 | Published: 23 February 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Hypertrophic cardiomyopathy is the most frequent autosomal dominant disease, yet due to genetic heterogeneity, incomplete penetrance, and phenotype variability, the prognosis of the disease course in pathogenic variant carriers remains an issue. Identifying common patterns among the effects of different genetic variants is important. Methods: We investigated the cause of familial hypertrophic cardiomyopathy (HCM) in a family with two patients suffering from a particularly severe disease. Searching for the genetic variants in HCM genes was performed using different sequencing methods. Results: A new missense variant, p.Leu714Arg, was identified in exon 19 of the beta-myosin heavy chain gene (MYH7). The mutation was found in a region that encodes the ‘converter domain’ in the globular myosin head. This domain is essential for the conformational change of myosin during ATP cleavage and contraction cycle. Most reports on different mutations in this region describe severe phenotypic consequences. The two patients with the p.Leu714Arg mutation had heart failure early in life and died from HCM complications. Conclusions: This case presents a new likely pathogenic variant in MYH7 and supports the hypothesis that myosin converter mutations constitute a subclass of HCM mutations with a poor prognosis for the patient.

hypertrophic cardiomyopathy
myosin converter domain
Max-Planck Society (Germany)
Fig. 1.
Back to top