The correlation between Arg186Gln mutation of TNNI3 gene and familial hypertrophic cardiomyopathy
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摘要: 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。Abstract: 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.
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Key words:
- hypertrophic cardiomyopathy /
- TNNI3 gene /
- Arg186Gln /
- mutation
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[1] 黄纬凌,杨俊.肥厚型心肌病治疗新进展[J].临床心血管病杂志,2016,32(8):766-768.
[2] Maron BJ,Shirani J,Poliac LC,et al.Sudden death in young competitive athletes.Clinical,demographic,and pathological profiles[J].JAMA,1996,276(3):199-204.
[3] Van der Velden J,Ho CY,Tardiff JC,et al.Research priorities in sarcomeric cardiomyopathies[J].Cardiovasc Res,2015,105(4):449-456.
[4] 丁春丽.肥厚型心肌病患者扩张相的特征与生存状况研究[J].临床心血管病杂志,2017,33(2):133-136.
[5] 赵新涛,吴亚杰,陈伊,等.β肌球蛋白重链基因Pro731Ser突变与家族型肥厚型心肌病的相关性研究[J].中华心血管病杂志,2014,42(7):571-576.
[6] 张兆国.关于肥厚型心肌病诊断和猝死防治建议(2014ESC指南节选)[J].实用心电学杂志,2016,25(1):1-5.
[7] Ho CY,Seidman CE.A contemporary approach to hypertrophic cardiomyopathy[J].Circulation,2016,113(24):858-862.
[8] Maron BJ,Maron MS.Hypertrophic cardiomyopathy[J].Lancet,2014,381:242-255.
[9] 苟成,刘金秋.肥厚型心肌病少见亚型:左心室中部梗阻性肥厚型心肌病[J].临床心血管病杂志,2016,32(12):1263-1265.
[10] 朱静,徐建.心肌纤维化定量分析方法[J].安徽医科大学学报,2012,47(11):1365-1368.
[11] 王忠振,夏云龙,杨延宗.心脏磁共振成像技术对心脏衰竭患者心肌纤维的评估及临床运用[J].心血管病学进展,2013,34(1):104-107.
[12] Green JJ,Berger JS,Kramer CM,et al.Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy[J].JACC Cardiovasc Imaging,2012,5(4):370-377.
[13] Rubinshtein R,Glockner JF,Ommen SR,et al.Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy[J].Cire Heart Fail,2010,3(1):51-58.
[14] Moravshy G,Ofek E,Rakowski H,et al.Myocardial fibrosis in hypertrophic cardiomyopathy accurate reflection of histopathological findings by CMR[J].JACC Cardiovasc Imaging,2013,6(5):587-596.
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