多样性和体细胞突变患病率促甲状腺素受体和Gsα基因毒性甲状腺腺瘤的一个原因。
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迪普雷帕尔马J L自己叙说,范Sande J,何曼思J, Rocmans P, Van Vliet G, Costagliola年代,Rodien P,杜蒙我Vassart G
多样性和体细胞突变患病率促甲状腺素受体和Gsα基因毒性甲状腺腺瘤的一个原因。
中国性金属底座。1997年8月,82 (8):2695 - 701。
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9253356 (在PubMed]
- 文摘
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共有33个不同自治热结节31例,主要产自比利时,调查是否存在体细胞突变的TSH受体和Gsα基因。这就构成了我们之前研究的延伸,包括前11系列的结节。TSH受体基因的完整编码序列和Gsα的片段包含突变削弱guanosinetriphosphotase活动研究通过直接测序基因组DNA提取的结节。juxtanodular组织或外周白细胞的DNA分析所有患者确认标识的突变体。27(82%)被发现在TSH受体突变基因,影响共有12种不同的残留物或位置。所有这些突变但前面2(见下文)已确定为激活突变。只有2突变被发现在Gsα(6%)。在4个结节,没有检测到突变。五残留物(Ser281 Ile486、Ile568 Phe631,和Asp633)突变被发现在3或4不同的结节,使它们为激活突变热点。Phe631 Asp633属于一群5连续残留物(629 - 633)的n端一半的跨膜段第六; which harbor together 44% of the mutations identified in this cohort. Two novel mutations were identified: a point mutation causing substitution of Phe for Leu at position 629 (L629F); and a deletion of 12 bases removing residues 658-661 at the C-terminal portion of exoloop 3 (del658-661). When tested by transfection in COS-7 cells, both mutant receptors display increase in constitutive stimulation of basal cAMP accumulation. Although it is still capable of binding TSH, the del658-661 mutant has completely lost the ability to respond to the stimulation by the hormone. Our results demonstrate that, in a cohort of patients from a moderately iodine deficient area, somatic mutations increasing the constitutive activity of the TSH receptor are the major cause of autonomous hot nodules.