心脏肌球蛋白结合蛋白C基因P1208fs突变与家族性肥厚型心肌病的关系  

P1208fs mutation in the cardiac myosin binding protein C is associated with hypertrophic cardiomyopathy in a Chinese pedigree

作　　者：李静[1] 刘丽文[2] 纳丽莎[5] 左蕾[2] 齐伟[2] 刘莹[3] 邵红[4] 马志玲[4] 王立锋[6] 

机构地区：[1]宁夏医科大学研究生院,银川750004 [2]第四军医大学西京医院超声科 [3]第四军医大学西京医院放射科 [4]第四军医大学西京医院心电图室 [5]宁夏医科大学总医院心脏中心功能检查部超声心动图室 [6]第四军医大学基础医学院生物化学与分子生物学教研室

出　　处：《中华心血管病杂志》2016年第4期321-326,共6页Chinese Journal of Cardiology

基　　金：科技部国家国际合作专项（2014DFA31980）;国家自然科学基金（81170305,30371571,81470452）;陕西省国际科技合作项目（2013KW33-03）

摘　　要：目的 研究中国汉族人群家族性肥厚型心肌病（HCM）的致病基因突变位点,分析基因型和临床表型的关系.方法 入选2013年7月就诊于第四军医大学西京医院心内科门诊的中国汉族家族性肥厚型心肌病一家系,该家系共有3代10位有血缘关系的成员.利用靶向外显子捕获测序的方法对HCM先证者的96个与遗传性心肌病相关的基因进行了全部外显子扩增和高通量测序,进一步通过Sanger测序法在家系内9名成员以及300个健康志愿者中进行了验证.家系资料收集包括临床表现、体格检查、心电图、超声心动图和心脏核磁共振检测结果.结果 本家系中共发现了3种基因突变,分别为心脏肌球蛋白结合蛋白C（MYBPC3）基因P1208fs突变、锚蛋白B（ANK2）基因H556R突变和错蛋白B（ANK2）基因P1974H突变.包括先证者在内的3名家系成员（还包括其母和其子）携带基因MYBPC3基因P1208fs突变.其余家系成员未发现此突变.先证者及其母亲通过心电图、超声心动图及心脏核磁共振诊断为HCM,其子为HCM早期表现,即常规超声心动图及心脏核磁共振未见异常,而心电图显示为窦性心动过缓不齐、ST段改变、房性早搏及逸搏.先证者及其母亲确诊为HCM的年龄分别为42岁和50岁,均伴有心悸、胸痛的症状,心脏核磁共振均提示为左心室部分心肌纤维化.进一步发现,先证者及其母亲左心室心肌纤维化与心电图改变（r波递增不良、ST-T改变）存在一定的关系.此外,携带ANK2突变基因的7名家系成员心电图QTc间期均正常.结论 MYBPC3基因P1208fs突变可导致国人HCM,引起左心室心肌非对称性肥厚、节段性心肌纤维化及相应室壁ST-T改变,ANK2基因H556R和P1974H突变在本家系中没有相应的临床表型,可能不具致病性.Objective To identify the potential mutations in a Chinese pedigree with hypertrophic cardiomyopathy （HCM）,and to analyze the genotype-phenotype relationship in this pedigree.Methods Clinical history and physical examinations,electrocardiography （ECG）,echocardiography （UCG）,cardiac magnetic resonance （CMR） data were obtained from 10 members of a three-generation Chinese family with HCM.A total of 96 genes related to hereditary cardiomyopathy were detected by exon and boarding intron analyses in the proband using second-generation sequencing.Mutations identified in the proband were confirmed by bi-directional Sanger sequencing in the rest 9 family members and 300 healthy controls.Results Three mutations,including MYBPC3-P1208fs,ANK2-H556R and ANK2-P1974H,were identified in this pedigree.MYBPC3-P1208fs gene mutation was detected in 3 family members （proband,his mother and son）,while this mutation was not detected in the rest family members.HCM was diagnosed in the proband and his mother by ECG,UCG and CMR.Son of the proband demonstrated early phenotype of HCM：although UCG and CMR were normal,ECG showed sinus bradycardia and paroxysmal supraventricular arrhythmias as well as ST segment changes.The onset age of HCM diagnosis of the proband and his mother was 42 and 50 years old,presented with palpitation and chest pain,and myocardial fibrosis sign in CMR.Furthermore,we found that left ventricular myocardial fibrosis is related to ECG changes （increasing r wave,ST segment change） in the proband and his mother.No HCM phenotype was evidenced in the 7 family members carrying ANK2-H556R and ANK2-P1974H mutations.Conclusions Our results show that MYBPC3-P1208fs gene mutation is associated HCM phenotype in this Chinses pedigree.This mutation is associated with myocardial fibrosis and ST changes in HCM phenotype in this pedigree while ANK2-H556R and ANK2-P1974H mutations are not related to HCM phenotype in this family.

关 键 词：心肌病 肥厚性 基因型 表型 

分 类 号：R542.2[医药卫生—心血管疾病]