肥厚型心肌病MYH7基因Arg143Gln的突变分析

Mutation Analysis of MYH7 Gene Arg143Gln in Hypertrophic Cardiomyopathy

摘要: 目的：筛查肥厚型心肌病(HCM)致病基因突变位点并解析该突变的特点和临床症状，以期为HCM的基因诊断和治疗提供理论支持。方法：采集患者家系的血液样本并收集其临床资料，对先证者采取全外显子组测序方法，利用Sanger测序法对先证者的致病突变位点在家系及307名正常对照组人群中验证，结合文献报道，通过同源性比对和多种生物信息学方法分析该突变的致病性。结果：全外显子组测序发现先证者携带β肌球蛋白重链基因(MYH7) c.G428A突变，该家庭中3人携带该突变，2人被诊断为HCM，表现出HCM特征性临床表现，其他家人及对照组人群均未发现上述突变。不同物种同源性比对提示该位点的所编码的第146位氨基酸具有高度保守性，不同生物信息学方法分析该突变位点是有害突变。结论：MYH7基因c.G428A是有害突变，发病患者可能会表现出严重临床表现，具有致病性。

Abstract: Objective: To screen the pathogenic gene mutation of hypertrophic cardiomyopathy (HCM) and an-alyze the characteristics and clinical symptoms of the mutation, in order to provide theoretical support for the genetic diagnosis and treatment of HCM. Methods: Blood samples from the patient’s family were collected and their clinical data were collected. Whole exome sequencing was used for the proband, and Sanger sequencing was used to verify the proband’s pathogenic mutation in the family and 307 normal control populations, combined with literature reports, the pathogenicity of the mutation was analyzed by homology alignment and various bioinformatics methods. Results: Whole exome sequencing revealed that in the proband carried the c.G428A mutation in the β-myosin heavy chain gene (MYH7), 3 members of the family carried the mutation, and 2 were di-agnosed with HCM, showing the characteristic clinical manifestations of HCM. The above mutations were not found in other family members and the control group. The homology alignment of differ-ent species indicated that the 146th amino acid encoded by this site is highly conserved, and dif-ferent bioinformatics methods analyzed the mutation site as a deleterious mutation. Conclusion: MYH7 gene c.G428A is a deleterious mutation that is pathogenic in patients with severe clinical manifestations.