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Updated: Oct 5, 2025

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

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

Published on: August 8, 2022

3.8K

Effect of Cis-Compound Variants in MYH7 on Hypertrophic Cardiomyopathy With a Mild Phenotype

Mo Zhang1, Xiaolu Sun1, Guixin Wu2

  • 1Department of Cardiology.

The American Journal of Cardiology
|January 23, 2022
PubMed

Insights

Compound variants in the MYH7 gene can cause hypertrophic cardiomyopathy (HC). This study found cis-compound variants (Met822Thr and Arg1420Trp) are causal but relatively benign in a Chinese family.

Area of Science:

  • Genetics
  • Cardiology
  • Molecular Biology

Background:

  • Hypertrophic cardiomyopathy (HC) patients with compound variants show severe manifestations but clinical heterogeneity.
  • This diversity may stem from varying combinations of genetic variants.
  • Understanding variant interactions is crucial for genotype-phenotype correlations in HC.

Purpose of the Study:

  • To investigate the role of cis-compound variants in the MYH7 gene within a Chinese hypertrophic cardiomyopathy pedigree.
  • To analyze the genotype-phenotype relationship associated with specific cis-compound variants in MYH7.

Main Methods:

  • Exome sequencing was performed on the proband.
  • Bi-directional Sanger sequencing was used to analyze variants in a 3-generation, 28-member pedigree.
  • A 16-year follow-up was conducted on affected family members.

Main Results:

  • Two pathogenic missense variants (c.2465T>C, p.Met822Thr; c.4258C>T, p.Arg1420Trp) in the MYH7 gene were identified.
  • These cis-compound variants were present in 11 family members; 5 developed HC, while 6 remained asymptomatic carriers with abnormal ECGs.
  • HC patients exhibited mild hypertrophy (13-21 mm wall thickness) and a low incidence of cardiovascular events.

Conclusions:

  • Cis-compound variants Met822Thr and Arg1420Trp in MYH7 are causal for familial HC but associated with relatively benign clinical outcomes.
  • Different types of compound variants may require distinct analyses for accurate genotype-phenotype studies in HC.
  • This study highlights the importance of considering variant combinations in understanding HC heterogeneity.

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