TNNI3基因Arg186Gln突变与家族性肥厚型心肌病的相关性分析

The correlation between Arg186Gln mutation of TNNI3 gene and familial hypertrophic cardiomyopathy

目的:研究中国汉族人群家族性肥厚型心肌病(HCM)常见致病基因突变位点,并对基因型与临床表型关系进行分析。方法:利用靶向外显子捕获测序方法对9例家族性HCM家系先证者进行MYH7、MYBPC3、TNNT2及TNNI3基因全外显子扩增和高通量测序,使用Sanger测序法在家系内进行验证。对阳性结果患者进行家系调查研究,调查资料包括一般临床症状、心电图、超声心动图以及3.0T心脏磁共振。进行门诊或电话定期随访,随访时间为1年或至患者死亡。结果:在其中1个家系中发现TNNI3基因第8号外显子Arg186Gln突变,该突变使遗传密码发生G→A转变,从而使其所编码的186位氨基酸由精氨酸(Arg)变为谷氨酰胺(Gln)。该家系中除先证者外还存在2例HCM患者,先证者为体检时发现心电图异常前来就诊,无临床症状,其父时有胸闷,在研究调查过程中猝死,其祖母胸闷气促症状明显。健康对照组中未发现上述基因突变。结论:家族性HCM患者TNNI3基因突变位点为Arg186Gln,携带该突变基因型的HCM患者呈现的临床表型不同,具有明显的临床异质性。

Objective：To research the TNNI3 gene＇s mutational site of familial hypertrophic cardiomyopathy（HCM）in Chinese Han population and to analyze the relationship between genotype and clinical phenotype.Method：Targeted exons capture sequencing method was used to sequence all exons extending and high through-put of TNNT2,MYBPC3,MYH7 and TNNI3 gene in 9 cases with familial HCM,and Sanger sequencing method was used to verify in family.Family research was conducted in those with positive result patients,data included general clinical symptoms,electrocardiogram,echocardiogram and 3.0 Tcardiac magnetic resonance were collected.Regular outpatient and phone follow-up lasted for 1 years or until death.Result：The Arg186 Gln mutation of TNNI3 gene＇s exon 8 was identified in one family,the mutation caused the genetic code to change from G to A,which converted from arginine（Arg）to glutamine（Gln）.Moreover,there were 2 HCM patients in the family excepted the propositus.The propositus had no clinical symptoms,and went to see a doctor because of abnormal electrocardiogram during physical examination,his father sometimes suffered chest distress and was sudden death during the research,while his grandmother suffered chest distress and shortness of breath,obviously.The aforementioned mutation was not found in health control group.Conclusion：The TNNI3 gene＇s mutational site of familial HCM is Arg186 Gln,HCM patients who carried the mutant gene show different clinical phenotypes,the clinical heterogeneity is obvious.