作　　者： (陈培）; (闫继锋）;

机构地区： 郑州大学第五附属医院,郑州,450052

出　　处： 《山东医药》

摘　　要： 目的 观察1个中国汉族肥厚型心肌病(HCM)家系的基因突变类型,并探讨其对临床表型的影响.方法 选择1个中国汉族HCM家系,家系成员共13例,其中5例确诊为HCM.采用新一代高通量测序技术检测先证者外周血44个心肌病靶基因,结果显示其存在β肌球蛋白重链7(MYH7)基因18号外显子Arg663His突变及肌钙蛋白I3(TNNI3)基因7号外显子c.470C>T突变.采用双脱氧末端终止法测序检测该家系中其他成员上述两个基因的突变情况,分析不同MYH7、TNNI3基因突变的HCM患者的临床表现.结果 先证者与其妹妹均存在MYH7基因18号外显子Arg663His及TNNI3基因7号外显子c.470C>T双突变,HCM发病年龄分别为2、1岁;心电图均示异常Q波,ST-T改变,左室高电压;超声心动图均示左房增大,室间隔中段以上最厚处分别为25、23 mm,SAM征阳性,左室流出道压差分别为80、68 mmHg.先证者的母亲、二舅及外公仅MYH7基因18号外显子Arg663His突变,HCM发病年龄分别为21、19、30岁;心电图均示ST-T改变,左室高电压;超声心动图均示室间隔增厚,最厚处分别为16、18、18 mm,SAM征阴性,无左室流出道梗阻.先证者表弟仅MYH7基因18号外显子Arg663His突变,临床无明显症状,心电图及超声心动图检查无异常.结论 该汉族HCM家系TNNI3基因发生从头突变,MYH7基因突变由遗传而来;MYH7与TNNI3基因双突变者HCM发病时间早、临床症状严重、预后较差. Objective To observe the gene mutation types in a Chinese Han hypertrophic cardiomyopathy (HCM) family and to explore its effect on clinical phenotype.Methods We selected 1 Chinese Han HCM family, including 13 family members, among whom 5 were diagnosed as HCM.New generation of high-throughput sequencing technology (NGS) was used to sequence the 44 genes of the target genomes associated with human cardiomyopathy of the proband.The results indicated that the proband carried β-myosin heavy chain (MYH7) gene Arg663His in exon 18 and troponin I (TNNI3) gene c.470C>T in exon 7.The mutations of the two genes in other members of the family were detected by the dideoxy chain-termination method, and the clinical manifestations of HCM patients with MYH7 and TNNI3 gene mutations were analyzed.Results The proband and his sister carried MYH7 gene exon 18 Arg663His mutation and TNNI3 gene exon 7 c.470C> T mutation, and the age of onset was respectively 2 and 1 years old.The ECG showed abnormal Q wave, ST-T changes, and left ventricular high voltage.Echocardiography showed left atrium enlargement, the thickest part of interventricular septum was 25 and 23 mm, SAM was positive, and the left ventricular outflow pressure were 80 and 68 mmHg, respectively.The proband''s mother, uncle and grandfather carried Arg663His mutation in MYH7 gene exon 18, and the age of onset was 21, 19, and 30 years old, respectively.The ECG showed ST-T changes and left ventricular high voltage.Echocardiography showed that the thickest part of interventricular septum were 16, 18, and 18 mm, respectively, SAM were negative, and no left ventricular outflow tract obstruction.The proband′s cousin only carried Arg663His mutation in MYH7 gene exon 18.There were no obvious clinical symptoms, and no abnormalities in ECG and echocardiogram.Conclusions The TNNI3 gene in the HCM family underwent de novo mutation, and the MYH7 gene mutation was inherited.The patients with double mutations of MYH7 and TNNI3 gene presented a younger onset age, severe clinical phenotype and poor prognosis.

分 类 号： [R542.2]