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Updated: Dec 25, 2025

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

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MYH7B variants cause hypertrophic cardiomyopathy by activating the CaMK-signaling pathway

Peng Chen1,2, Zongzhe Li1,2, Jiali Nie1,2

  • 1Division of Cardiology, Departments of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Science China. Life Sciences
|March 25, 2020
PubMed

Insights

Genetic variants in MYH7B are identified as a cause of hypertrophic cardiomyopathy (HCM), a common heart disease. This discovery reveals a new genetic contributor to HCM, impacting 1.46% of patients studied.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Genetic Diseases

Background:

  • Hypertrophic cardiomyopathy (HCM) is a prevalent genetic heart condition.
  • Mutations in cardiac sarcomere genes are the primary known cause of HCM.
  • The role of MYH7B in causing HCM remained previously unknown.

Purpose of the Study:

  • To investigate the potential role of MYH7B variants in the pathogenesis of hypertrophic cardiomyopathy.
  • To identify novel genetic causes of HCM beyond known sarcomere gene mutations.

Main Methods:

  • Screening of 549 unrelated HCM patients and 500 healthy controls using targeted and whole exome sequencing.
  • Generation and functional analysis of Myh7b knockout rat models.
  • Cardiac function assessment via Millar pressure-volume catheterization and echocardiography.
  • Transcriptome sequencing and signaling pathway analysis (CaMK-signaling).

Main Results:

  • Seven MYH7B variants were identified in 8/549 HCM patients (1.46% of cases).
  • Three likely pathogenic MYH7B variants co-segregated with HCM in three pedigrees.
  • Myh7b knockout rats exhibited spontaneous HCM phenotypes, cellular disarray, and cardiac fibrosis.
  • Calcium and the CaMK-signaling pathway were identified as key mediators in Myh7b-deficient cardiac hypertrophy.

Conclusions:

  • This study provides the first evidence that MYH7B variants can cause hypertrophic cardiomyopathy.
  • MYH7B mutations represent a significant, previously unrecognized genetic cause of HCM.
  • The CaMK-signaling pathway is implicated in the pathophysiology of MYH7B-associated HCM.

Keywords:
CaMK-signaling pathwayMYH7Bhypertrophic cardiomyopathytranscriptome sequencingwhole exome sequencing

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