β肌球蛋白重链基因Arg249Gln突变导致家族性肥厚型心肌病基因型与表型分析  

A GENOTYPE-PHENOTYPE ANALYSIS OF FAMILIAL HYPERTROPHIC CARDIOMYOPATHY CAUSED BY ARG249GLN MUTATION IN THE β-MYOSIN HEAVY CHAIN GENE

作　　者：焦俊杰 刘荟婷 单正宜 吕家磊 信芳杰[2] 赵鹏[2] JIAO Junjie;LIU Huiting;SHAN Zhengyi;Lü Jialei;XIN Fangjie;ZHAO Peng(Forensic Medicine,School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院,山东青岛266071 [2]青岛大学附属医院病理科,山东青岛266071

出　　处：《青岛大学学报（医学版）》2023年第1期38-42,共5页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(81570270)。

摘　　要：目的筛查家族性肥厚型心肌病(HCM)致病突变基因,分析基因型与临床表型相关性。方法采用全外显子测序技术对一HCM家系先证者编码肌节蛋白的8个致病基因进行分析,利用Sanger测序法对发现的突变位点在该家系的14名家庭成员及307名健康对照者中进行验证。结果遗传筛查发现先证者携带β肌球蛋白重链(MYH7)基因c.746G>A(Arg249Gln)突变。家系中4人携带该突变,3人确诊为HCM,携带者均有严重的临床表型,2人因HCM发生猝死。在307名健康对照者中没有检出MYH7基因Arg249Gln突变。结论MYH7基因Arg249Gln突变可能是导致该家系家族性HCM的恶性突变,该突变携带者临床表型较严重。Objective To investigate the pathogenic mutation genes for familial hypertrophic cardiomyopathy(HCM)and the association between genotypes and clinical phenotypes.Methods Whole-exome sequencing was used to analyze the 8 pathogenic genes encoding sarcomeric proteins in the proband of a family with HCM,and Sanger sequencing was used to validate the mutation sites in 14 family members and 307 unrelated healthy controls.Results Genetic screening revealed that the proband carried the c.746G>A(p.Arg249Gln)mutation of theβ-myosin heavy chain(MYH7)gene.Four individuals in this family carried this mutation,and three of them were diagnosed with HCM.All of the carriers had a severe clinical phenotype,and two individuals experienced sudden death due to HCM.The Arg249Gln mutation of MYH7 was not detected in 307 healthy controls.Conclusion The Arg249Gln mutation of MYH7 may be a malignant mutation gene leading to familial HCM,and carriers of this mutation tend to have severe clinical phenotypes.

关 键 词：心肌病 肥厚性 猝死 肌球蛋白重链 突变 遗传关联研究 

分 类 号：R542.2[医药卫生—心血管疾病] R394-33[医药卫生—内科学]