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Updated: Aug 20, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Mutations profile in Chinese patients with hypertrophic cardiomyopathy
Lei Song1, Yubao Zou, Jizheng Wang
1Sino-German Laboratory for Molecular Medicine, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Insights
Genetic analysis of hypertrophic cardiomyopathy (HCM) in China reveals MYH7 and MYBPC3 as predominant genes, with novel mutations identified. This highlights population-specific genetic diversity in HCM.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genetic Epidemiology
Background:
- Hypertrophic cardiomyopathy (HCM) affects over 1 million patients in China.
- The genetic underpinnings of HCM in the Chinese population remain largely uncharacterized.
Purpose of the Study:
- To identify the genetic basis of HCM in Chinese patients.
- To investigate the spectrum of mutations in key HCM-associated genes.
Main Methods:
- Targeted gene sequencing of MYH7, MYBPC3, and TNNT2 in 100 unrelated Chinese HCM patients.
- Analysis of mutation prevalence, types, and genotype-phenotype correlations.
Main Results:
- 34% of patients carried mutations in the studied genes, with 14 out of 25 mutations being novel.
- MYH7 (41%) and MYBPC3 (18%) were the primary drivers of familial HCM.
- MYH7 mutations were associated with earlier onset and more severe symptoms compared to MYBPC3.
Conclusions:
- Significant genetic heterogeneity exists in Chinese HCM patients, distinct from other populations.
- MYH7 and MYBPC3 are key genes in Chinese HCM, while TNNT2 plays a minor role.
- A global registry is needed to correlate HCM genotypes with phenotypes across diverse populations.
Background:
There are more than 1 million patients with hypertrophic cardiomyopathy (HCM) in China, but the genetic basis is presently unknown.
Methods:
We investigated 100 independent patients with HCM (proband 51, sporadic 49) by sequencing the three most frequent HCM-causing genes (MYH7, MYBPC3, TNNT2).
Results:
Thirty-four patients (34%) carried 25 types of mutations in the selected genes, most (14/25) were newly identified. MYH7 and MYBPC3 accounted for 41% and 18% of the familial HCM, respectively. TNNT2 mutations only caused 2% of the familial HCM. These results suggested that MYH7 and MYBPC3 were the predominant genes responsible for HCM, and TNNT2 mutation less proportionally contributed to Chinese HCM. MYH7 mutations caused HCM at younger age, more frequent syncope and ECG abnormalities compared with MYBPC3 mutations. The patients carrying R663C, Q734P, E930K in MYH7 and R130C in TNNT2 expressed malignant phenotype. R403Q in MYH7, the most common hot and malignant mutation in Caucasians, was not identified in Chinese.
Conclusion:
We confirmed the diversity of mutation profile in different populations and suggest that a global registry of HCM mutations and their phenotypes is necessary to correlate genotype with phenotype.
