Related Experiment Video
Updated: May 10, 2025
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
MYH7 Mutations in Restrictive Cardiomyopathy
Yiqi Zhao1, Shun Liu1, Han Mo2
1Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Restrictive cardiomyopathy (RCM) is a rare cardiac disease characterized by impaired ventricular filling and relaxation, with preserved systolic function. This study investigates the genetic basis of RCM and its impact on clinical outcomes, particularly heart transplantation (HTx).
Objectives:
The aim of the study was to identify genetic variations associated with RCM and assess their impact on disease progression and HTx necessity.
Methods:
A retrospective analysis was conducted on 94 RCM patients from Fuwai Hospital (2003-2021), diagnosed via echocardiography or pathological examination. Whole exome sequencing screened patient samples for variants in key genes associated with RCM, validated via Sanger sequencing. Histopathological analysis of explanted hearts included systematic sampling from ventricles and interventricular septum, with Masson's trichrome staining for fibrosis quantification.
Results:
Genetic variants were identified in 54% of patients, with a higher prevalence in HTx patients (73%) compared to non-HTx patients (27%). Myosin heavy chain 7 (MYH7) mutations were found in 15% of cases, significantly associated with HTx (P < 0.001) and atrial fibrillation (P = 0.025). Patients with MYH7 mutations exhibited extensive fibrosis in the interventricular septum compared to nonmutation patients (P < 0.05). The mean age at diagnosis was 47.8 years, with HTx patients diagnosed at a younger age (mean 36.0 years) and transplanted at a mean age of 37.4 years, compared to non-HTx patients diagnosed at a mean age of 57.9 years. The median follow-up time was 5 years.
Conclusions:
Genetic variations, particularly in the MYH7 gene, are significant risk factors for RCM progression and HTx. Genetic screening may guide early interventions, while fibrosis and MYH7 pathways offer potential therapeutic targets.
