目的 研究中国人家族性肥厚型心肌病(HCM)的致病基因,分析基因型与临床表型的关系.方法 以2016年青岛市第三人民医院心内科1例住院患者为先证者的HCM家系,在此HCM家系中进行了包括心脏型肌球蛋白结合蛋白C(MYBPC3)在内的30个HCM相关的致病基因的编码区及侧翼区进行了检测,利用靶向外显子捕获测序的方法对HCM先证者的30个与遗传性心肌病相关的基因进行全外显子扩增和高通量测序,进一步通过Sanger测序法在家系内及200名健康志愿者中进行验证.家系调查资料包括临床表现、体格检查、心电图及超声心动图.结果 该家系共6人,有血缘关系的4例研究对象中,3例携带MYBPC3基因c.G772A杂合错义突变,该突变位点位于MYBPC3基因第6号外显子上,并使258位的谷氨酸(E)变为赖氨酸(K),该家系先证者携带MYBPC3突变,中年发病,临床表型温和,超声示室间隔明显增厚(厚度为18.3 mm).结论 MYBPC3基因c.G772A杂合错义突变可能是该HCM家系的致病突变,其携带者临床表型温和,有的无临床表现,提示其他因素如其他基因、年龄、环境等因素参与了HCM的发展过程.%Objective To study the pathogenic gene of Chinese familial hypertrophic cardiomyopathy (HCM),and to analyze the relationship between genotype and clinical phenotype.Methods One inpatient treated in Department of Cardiology,the Third People's Hospital of Qingdao in 2016 was taken as the HCM family of proband,in which,the coding region and flanking region of 30 virulence gene related to HCM including cardiac myosin binding protein C (MYBPC3) were detected,and the 30 genes related to hereditary cardiomyopathy of HCM proband were identified by whole exons amplification and high-throughput sequencing through targeted exon trapping sequencing,and the identified mutation was further detected through bi-directional Sanger sequencing in the family members and 200 healthy volunteers.Pedigree analysis included clinical manifestation,physical examination,ECG and echocardiogram.Results Among 4 bloodrelated members in the six members of family,3 members had MYBPC3 gene c.G772A hybrid missense mutation.The mutation was existed in the 6th exon of MYBPC3 gene,which made a 258-bit glutamic acid (E) into a lysine (K).The proband of the family carried on MYBPC3 mutation,who was attacked in the middle-age,clinical phenotype was mild,and the ultrasound showed that the interventricular septum was significantly thickened (the thickness was 18.3 mm).Conclusion MYBPC3 gene c.G772A hybrid missense mutation may be the pathogenic mutations of this HCM family.Some carriers have mild clinical phenotype,and some have no clinical manifestation,which suggests that other factors such as other genes,age,environment also participate in the development process of HCM.
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