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Updated: Nov 26, 2025
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy
Lazar Velicki1,2, Djordje G Jakovljevic3,4, Andrej Preveden5,6
1Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. lazar.velicki@mf.uns.ac.rs.
Insights
Patients with MYH7 gene mutations in hypertrophic cardiomyopathy (HCM) show more severe disease than those with MYBPC3 mutations. This genetic disorder impacts cardiovascular health, with distinct clinical presentations based on the specific gene involved.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiovascular disease affecting approximately 1 in 500 individuals.
- Genetic mutations, particularly in MYBPC3 and MYH7 genes, are the primary cause of HCM, accounting for about 75% of identified cases.
Purpose of the Study:
- To investigate the association between specific genetic mutations (MYBPC3 vs. MYH7) and the clinical phenotype in patients with HCM.
- To compare clinical characteristics and echocardiographic findings between patients with MYBPC3 and MYH7 mutations.
Main Methods:
- The study included patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes.
- Patients were divided into MYBPC3 (76%) and MYH7 (24%) groups, undergoing clinical examination and echocardiography.
- The SILICOFCM project provided the framework for this international, multidisciplinary research.
Main Results:
- Dyspnea was more common in the MYBPC3 group (44%), while palpitations were more frequent in the MYH7 group (33%).
- MYH7 mutation carriers exhibited higher prevalence of systolic anterior motion (33%), mitral leaflet abnormalities (40%), and mitral annulus calcifications (20%).
- Patients with MYH7 mutations showed numerically higher rates of atrial fibrillation (60%) and more pronounced diastolic dysfunction (E/e' ratio of 13.9 ± 6.9).
Conclusions:
- The study supports the concept that MYH7 gene mutations are associated with more severe disease manifestations in HCM compared to MYBPC3 mutations.
- Distinct clinical and echocardiographic phenotypes correlate with specific genetic mutations in HCM, aiding in personalized patient management.
Background:
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.
Methods:
As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.
Results:
The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079).
Conclusions:
Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.
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