Zhao Xueli, Wang Bo, Zhu Xiaoli, Yang Qianli, Liu Ying, Shao Hong, Zuo Lei, Luo Yun, Wang Yue, Liu Liwen
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.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Aug 10;39(8):873-876. doi: 10.3760/cma.j.cn511374-20210317-00239.
To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM).
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.
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).
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.
分析一个中国肥厚型心肌病（HCM）家系的临床表型及MYH7基因变异情况。
先证者通过外显子扩增和高通量测序对96个心肌病相关基因的变异进行筛查。候选变异通过Sanger测序在300名健康对照者以及先证者的家庭成员中进行验证。对该家系进行基因型和临床表型的共分离分析。使用Clustal X软件分析该变异在不同物种间的序列保守性，并使用生物信息学软件预测其致病性。
该家系12名成员中有6名携带MYH7基因杂合c.4124A>G（p.Tyr1375Cys）变异，其中5名被诊断为HCM。其余1名未达到HCM诊断标准，但心电图异常。300名健康对照者中未发现相同变异。氨基酸序列分析显示该变异位于高度保守区域，生物信息学分析预测此变异可能影响蛋白质功能且具有有害作用。根据美国医学遗传学与基因组学学会（ACMG）指南，该变异被预测为可能致病（PM2 + PP1_Moderate + PP3 + PP5）。
MYH7基因的c.4124A>G（p.Tyr1375Cys）变异可能是该家系发病机制的基础。上述发现对HCM患者的早期诊断具有重要价值。
