甲状腺激素抵抗由于小说甲状腺激素受体突变体在二级舌甲状腺和甲状腺功能减退患者突变体受体的功能特性。
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只是Y,山田M, Horiguchi K, Satoh T,桥本K, Tokuhiro E, Onigata K, Mori M
甲状腺激素抵抗由于小说甲状腺激素受体突变体在二级舌甲状腺和甲状腺功能减退患者突变体受体的功能特性。
甲状腺。2010年8月,20(8):917 - 26所示。doi: 10.1089 / thy.2009.0389。
- PubMed ID
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20615127 (在PubMed]
- 文摘
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背景:我们描述一例少见的先天性甲状腺功能减退和极高的血清促甲状腺素(TSH)水平的结合引起的抗甲状腺激素(仅仅)和舌甲状腺。R316C,因为仅仅的突变是新的,左旋甲状腺素的最佳剂量是不清楚。辅助治疗的评估,我们突变特征R316C甲状腺激素受体(TR),并与常见的突变,R316H,使用体外研究。简介:病人是一个新生的女性有严重的甲状腺功能减退与游离甲状腺素水平的0.36 ng / dL和血清TSH水平的177 microU /毫升。scintiscan显示异位甲状腺舌组织如果没有正常的甲状腺。与左旋甲状腺素补充剂量的> 350 microg /天没有正常血清TSH水平;然而,病人显示正常生长和情报在14岁。与计算机分析的结果一致,绑定的R316C三碘甲状腺氨酸(T3)显著下降到38%的野生型。电泳迁移率改变分析表明,像R316H R316C没有为形式,但与RXR异质二聚体形成的。然而,glutathione-S-transferase拉试验显示的绑定R316C NCoR没有T3和释放的T3受损。 In addition, transient transfection experiments demonstrated that unlike R316H, R316C had severe impairment of transcriptional activity on genes both positively and negatively regulated by thyroid hormone. It also had a clear dominant negative effect on genes negatively, but not positively, regulated by thyroid hormone, including the TSH-releasing hormone and TSHbeta genes. CONCLUSION: This is the first reported case of a R316C TR mutation. The characteristics of the R316C mutant differed from those of the R316H mutant. Our findings suggest that R316C causes reduced association with and impaired release of NCoR, resulting in RTH predominantly at the pituitary level, and that slightly elevated serum TSH level with high dose of levothyroxine might be optimum for normal growth.