心脏型肌球蛋白结合蛋白C p.L808M和c.2417_2419delACA基因突变与家族性肥厚型心肌病的关系

doi:10.6040/j.issn.1671-7554.0.2019.579

摘要/Abstract

摘要： 目的探讨肥厚型心肌病患者的致病基因突变位点,并对基因型与临床表型之间的关系进行分析。方法利用靶向外显子捕获测序的方法对73岁女性肥厚型心肌病先证者的26个与肥厚型心肌病(HCM)相关基因进行全外显子扩增和高通量测序,进一步通过Sanger测序法在基因突变家系内及100名健康志愿者中进行验证,确定该家系的致病突变位点。分析基因突变携带家系成员临床症状、体格检查、心电图及超声心动图检测结果,探究基因型与表型的关系。结果先证者心脏型肌球蛋白结合蛋白C基因(MYBPC3)第26号外显子上同时发现p.L808M和c.2417_2419delACA两个新突变位点。健康志愿者未见异常。该患者57岁始出现胸闷、心悸症状,家系中5例携带突变基因,其中2例为HCM患者,3例为无症状携带者,无心源性猝死家族史。结论基因突变序列分析,提示该家系基因突变引起蛋白功能改变的可能性大,MYBPC3 p.L808M和c.2417_2419delACA基因突变可能是该HCM家系的致病突变位点。

关键词: 心肌病, 肥厚型, 心脏型肌球蛋白结合蛋白C, 突变

Abstract: Objective To explore the disease-causing gene mutation of hypertrophic cardiomyopathy(HCM), and to analyze the correlation between the genotype and phenotype. Methods The exons in 26 HCM-related genes were amplified by target exon trapping sequencing and tested in one HCM proband to identify the pathogenic mutations. The identified mutations were detected with Sanger sequencing in all family members of the proband and 100 healthy volunteers. The clinical manifestations, physical examinations, electrocardiography and echocardiography were analyzed, and the relationship between genotype and phenotype was analyzed. Results Two mutations(p.L808M and c.2417_2419delACA)in the 26th exon of the MYBPC3 gene were identified in a 73-year-old female patient, but no such mutation was detected in the 100 healthy volunteers. The patient began to have symptoms of chest distress and palpitation since the age of 57. Totally 5 family members carried the mutant gene, including 2 HCM patients and 3 asymptomatic 山东大学学报 (医学版)57卷9期 -刘晓曼,等.心脏型肌球蛋白结合蛋白C p.L808M和c.2417_2419delACA基因突变与家族性肥厚型心肌病的关系 \=-carriers. No history of sudden cardiac death was observed. Conclusion Functional analysis of the sequences suggested that the double mutations may cause significant alteration of the protein function. MYBPC3 p.L808M and c.2417_2419delACA mutations may be the pathogenic mutations of this HCM family.

Key words: Cardiomyopathy, Hypertrophic, Cardiac myosin binding protein-C, Mutation

中图分类号:

R542.2

刘晓曼,李虹, 杨广, 金翠香. 心脏型肌球蛋白结合蛋白C p.L808M和c.2417_2419delACA基因突变与家族性肥厚型心肌病的关系[J]. 山东大学学报 (医学版), 2019, 57(9): 83-87.

LIU Xiaoman, LI Hong, YANG Guang, JIN Cuixiang. Relationship between cardiac myosin-binding protein p.L808M and c.2417_2419delACA gene mutation and familial hypertrophic cardiomyopathy[J]. Journal of Shandong University (Health Sciences), 2019, 57(9): 83-87.

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