The Mutation and Paterns of Subtypes of Troponin-T in Familial Hypertrophic Cardiomyopathy.

家族性肥厚型心肌病肌钙蛋白-T 亚型的突变和模式。

• 批准号: 11670783
• 负责人: ARAI Shoichi
• 金额: $ 2.11万
• 依托单位: International University of Health and Welfare
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670783/
• 关键词: hypertrophiccardiomyopathy; myocardial tropnin-T gene; cardiac β myosin heavy chain gene; gene mutation; 家族性肥大型心筋症; サルコメア収縮蛋白遺伝子; ミスセンス変異

The hypertrophic cardiomyopathy (HCM) is a myocardial disease that presents abnormal alignment of muscle cells called myocardial disarray and left ventricle hypertrophy. It has been shown that about 50 % of patients with HCM will have a first degree relative who also has the diagnosis of the HCM or the simple dominant inheritance. The frequency of the sudden death among patients is 2 - 4 % annually, and some suffers dramatic change.The purpose of this study was to establish the diagnostic procedure for HCM at early stage by detecting the missense mutation of myocardial troponin-T (Tn-T) gene, which was reported that occurued among approximately 15 % of the HMC families and caused fatal prognosis, and making it clear the relation between it and clinical symptoms.We analyzed 57 affected genes stored at the Tokyo Women's Medical University HMCfamilies' lymphocyte cell lines bank, and the results were compared with the clinical findings retrospectively. In result, we found out Tn-T mutatio … More ns (Arg92Trp, Phel 10Ile, Lys253Arg) in three families, cardiac β myosin heavy chain (β -MHC) mutation (Gly741Trp) in one family. We compared survival curves for subjective families calculated using the Kaplan-Meier method, then found out that the survival curve value of Tn-T Arg92Trp mutation family whose hypertrophy was seemed to be small from clinical findings was the lowest, and the value increased in β -MHC Gly741Trp mutation family, and Tn-T Phel 10Ile mutation family consistently. It was commonly believed that ventricle hypertrophy of Tn-T mutation patients is relatively small but they have a tendency of transition to dilated stage, but our results suggested that such a tendency depended upon the Tn-T mutation site. It was also suggested that there were different appearances in clinical, microscopic and electron microscopic findings among patients who had same mutation.We need more study to investigate the causes of symptomatic differences among HCM patients, intending to find out the way to delay the onset of such symptoms. Less

肥厚型心肌病 (HCM) 是一种心肌疾病，表现为心肌细胞排列异常，称为心肌紊乱和左心室肥大。研究表明，约 50% 的 HCM 患者的一级亲属也患有肥厚型心肌病。 HCM或单纯显性遗传患者猝死的频率每年为2-4%，并且有些患者发生剧烈变化。本研究的目的是建立HCM的诊断程序。通过检测心肌肌钙蛋白-T（Tn-T）基因的错义突变（据报道约15%的HMC家族中发生并导致致命的预后），早期诊断HCM，并明确其与临床症状的关系.我们分析了东京女子医科大学HMC家族淋巴细胞系库中储存的57个受影响基因，并将结果与​​临床结果进行回顾性比较，结果发现。三个家族中的 Tn-T 突变 (Arg92Trp、Phel 10Ile、Lys253Arg)，一个家族中的心脏 β 肌球蛋白重链 (β -MHC) 突变 (Gly741Trp) 我们比较了使用 Kaplan-Meier 计算的主观家族的生存曲线。方法，发现从临床表现来看肥大程度较小的Tn-T Arg92Trp突变家族的生存曲线值为β-MHC Gly741Trp 突变家族、Tn-T Phel 10Ile 突变家族的值最低，普遍认为 Tn-T 突变患者心室肥大程度较小，但有向扩张期过渡的趋势。 ，但我们的结果表明这种趋势取决于Tn-T突变位点，也表明具有相同突变的患者在临床、显微镜和电镜观察中存在不同的表现。我们需要更多。研究调查HCM患者症状差异的原因，旨在找出延缓此类症状出现的方法。

项目成果

Shoichi ARAI, Kunitaka Joh-o, Michiko Furutani, Shin-ichiro Imamura, Atsuyoshi Takao, Kazuo Momma, Rumiko Matsuoka: "Combined Missense Mutations of the Mitochondrial DNA Gene, β-Cardiac Heavy-Chain Gene and Cardiactropnin-T Gene in Familial Hypertrophic C

Shoichi ARAI、Kunitaka Joh-o、Michiko Furutani、Shin-ichiro Imamura、Atsuyoshi Takao、Kazuo Momma、Rumiko Matsuoka：“家族性肥厚症中线粒体 DNA 基因、β-心脏重链基因和心肌肌钙蛋白-T 基因的组合错义突变C

Shoichi ARAI, et,al,: "Combined Missense Mutations of the Mitochondrial DNA Gene, β-Cardiac Heavy-Chain Gene and Cardiactropnin-T Gene in Familial Hypertrophic Cardiomyopathy."Etiology and Morphogenesis of Congenital Heart Disease. 347-351 (2000)

Shoichi ARAI 等人：“家族性肥厚型心肌病中线粒体 DNA 基因、β-心脏重链基因和心肌肌钙蛋白 T 基因的组合错义突变。”先天性心脏病的病因学和形态发生 347-351 (2000)。

Shoichi ARAI, et,al,: "Combined Missense Mutations of the Mitochondrial DNA Gene, β-Cardiae Heavy-Chain Gene and Cardiactropnin-T Gene in Familial Hypertrophic Cardiomyopathy."Etiology and Morphogenesis of Congenital Heart Disease. 347-351 (2000)

Shoichi ARAI 等人：“家族性肥厚型心肌病中线粒体 DNA 基因、β-Cardiae 重链基因和心肌肌钙蛋白 T 基因的组合错义突变。”先天性心脏病的病因学和形态发生 347-351 (2000)。