Analysis of phenotype and MYH7 gene variant in a family of patients with hypertrophic cardiomyopathy.
10.3760/cma.j.cn511374-20210317-00239
- VernacularTitle:一个肥厚型心肌病家系患者的表型和
MYH7基因变异分析
- Author:
Xueli ZHAO
1
;
Bo WANG
;
Xiaoli ZHU
;
Qianli YANG
;
Ying LIU
;
Hong SHAO
;
Lei ZUO
;
Yun LUO
;
Yue WANG
;
Liwen LIU
Author Information
1. Hypertrophic Cardiomyopathy Center of Xijing Hospital of Air Force Medical University, Multi Disciplinary Consultation Center of Hypertrophic Cardiomyopathy of Shaanxi Province, Department of Ultrasonography, Xijing Hospital of Air Force Medical University, Xi'an, Shaanxi 710032, China. liuliwencrt@hotmail.com.
- Publication Type:Journal Article
- MeSH:
Cardiac Myosins/genetics*;
Cardiomyopathy, Hypertrophic/genetics*;
Genotype;
Humans;
Mutation;
Myosin Heavy Chains/genetics*;
Pedigree;
Phenotype
- From:
Chinese Journal of Medical Genetics
2022;39(8):873-876
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM).
METHODS:The proband was screened for variant of 96 cardiomyopathy-associated genes by exonic amplification and high-throughput sequencing. Candidate variant was verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. Co-segregation analysis of genotypes and clinical phenotypes was carried out for the pedigree. Clustal X software was used to analyze the sequence conservation of the variant among various species, and its pathogenicity was predicted by using bioinformatics software.
RESULTS:6 out of 12 members from this pedigree were found to harbor heterozygous c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene, among whom five were diagnosed with HCM. The remaining one had failed to meet the diagnostic criteria for HCM, but had abnormal ECG. The same variant was not found in the 300 healthy controls. Amino acid sequence analysis showed that the variant is located in a highly conserved region, and bioinformatics analysis predicted that this variant may affect protein function and has a deleterious effect. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM2+ PP1_Moderate+PP3+PP5).
CONCLUSION:The c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene probably underlay the pathogenesis in this pedigree. Above finding has important value for the early diagnosis of patients with HCM.
