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Updated: Jan 1, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Screening of MYH7 gene mutation sites in hypertrophic cardiomyopathy and its significance
Hui-Ting Liu1,2, Fang-Fang Ji3, Ling Wei4
1Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
Insights
This study identified two new mutations, Thr446Pro and Phe468Leu, in the MYH7 gene of fatal hypertrophic cardiomyopathy (HCM) patients. These findings are crucial for clinical and forensic applications in understanding HCM sudden cardiac death.
Area of Science:
- Genetics
- Cardiology
- Forensic Medicine
Background:
- Hypertrophic cardiomyopathy (HCM) is a significant cause of sudden cardiac death.
- Mutations in the beta-myosin heavy chain (MYH7) gene are infrequently reported in HCM.
- This study investigates MYH7 gene mutations in Chinese HCM patients.
Purpose of the Study:
- To screen for MYH7 gene mutation sites in Chinese patients with fatal HCM.
- To analyze the pathogenicity and clinical significance of identified MYH7 mutations.
- To explore the relevance of these mutations in forensic medicine.
Main Methods:
- Autopsy tissues from 18 fatal HCM cases and 20 control cases were analyzed.
- MYH7 gene exons were amplified using polymerase chain reaction.
- Mutation sites were identified using end-of-deoxygenation and gene cloning methods, with homologous comparison via BLAST.
Main Results:
- Two novel mutations in exon 14 of the MYH7 gene were identified in fatal HCM cases: T to G at nucleotide 1336 (Thr446Pro) and T to C at nucleotide 1402 (Phe468Leu).
- The affected amino acid residues, threonine at position 446 and phenylalanine at position 468, are highly conserved across species.
- These mutations were found in individuals who died suddenly from HCM.
Conclusions:
- Fatal HCM cases in this cohort harbored Thr446Pro and Phe468Leu mutations in the MYH7 gene.
- Further research into the function and mechanisms of these MYH7 mutations is warranted.
- These findings have implications for clinical diagnosis and forensic investigations of sudden cardiac death related to HCM.
Background:
There have been few reports of mutations in the beta-myosin heavy chain (MYH7) gene in hypertrophic cardiomyopathy (HCM), which is associated with sudden cardiac death caused by HCM. This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM. We also planned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine.
Methods:
From January 2006 to June 2017, autopsy cases were collected from the Department of Pathology, the Affiliated Hospital of Qingdao University. The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death (fatal HCM) and 20 cases without cardiomyopathy. Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction. The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites. Homologous comparison among mutant sites was conducted using BLAST online database.
Results:
The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case, resulting in the conversion of threonine (Thr) at position 446 to proline (Pro). In another case, the 1402th nucleotide at exon 14 was converted from T to C, resulting in the conversion of phenylalanine (Phe) at position 468 to leucine (Leu). Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species.
Conclusions:
Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene. It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations.
