小说促甲状腺素受体基因的激活突变的自主功能甲状腺结节病人由一个日本。
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Kosugi年代,海N,王小飞,Sugawa H, Mori T
小说促甲状腺素受体基因的激活突变的自主功能甲状腺结节病人由一个日本。
欧元J性。2000年10月,143 (4):471 - 7。
- PubMed ID
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11022192 (在PubMed]
- 文摘
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目的:大量的激活突变的促甲状腺素受体(TSHR)被发现在自主功能甲状腺结节(AFTNs)在欧洲的病人。我们旨在研究TSHR基因突变在日本病人因为没有TSHR AFTNs激活突变被发现之前不完整的研究。设计:一个典型的AFTN开发的69岁的日本妇女进行了研究。方法:对10 TSHR的cDNA全部外显子测序。功能研究都是基于定点诱变和突变构建成COS-7细胞的转染。结果:我们发现了一个新奇的杂合的TSHR基因突变,Leu512 - - >参数(L512R;从AFTN CTG - - > 20)。突变中没有检测到邻近的正常甲状腺组织。COS-7细胞转染L512R突变TSHR表达载体表现出增加3.3倍基础营水平与细胞转染野生型TSHR的DNA,确认了AFTN突变的直接原因。TSHR激活突变涉及第三跨膜螺旋迄今报告S505R / N和V509A L512R。 An in vitro site-directed mutagenesis study encompassing residues 505-513 revealed that mutations involving residues other than these three did not show constitutive activation. CONCLUSION: This is the first TSHR activating mutation found in a Japanese patient, although true prevalence of TSHR activating mutations in AFTNs developed in Japanese patients remains to be elucidated. In addition, functional studies suggested that amino acid residues in the third transmembrane helix maintaining inactive conformation of the TSHR seem to be located on the same surface of the alpha-helix, possibly making interhelical bonds with another helix.