A mutation in the DNA-binding domain of the androgen receptor gene causes complete testicular feminization in a patient with receptor-positive androgen resistance.
A mutation in the DNA-binding domain of the androgen receptor gene causes complete testicular feminization in a patient with receptor-positive androgen resistance.
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雄激素受体基因 DNA 结合域的突变会导致受体阳性雄激素抵抗患者的睾丸完全女性化。
DOI：
10.1172/jci115076
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
McPhaul,MJ
中科院分区：
文献类型：
--
作者：
Marcelli,M;Zoppi,S;Grino,PB;Griffin,JE;Wilson,JD;McPhaul,MJ
雄激素抵抗与雄激素受体的一系列数量和质量缺陷有关。然而，大约10%具有雄激素抵抗的临床、内分泌和遗传特征的患者的成纤维细胞培养在培养的生殖器皮肤成纤维细胞中表达正常数量的表面正常的雄激素受体(受体阳性雄激素抵抗)。我们分析了一例受体阳性、睾丸完全女性化的患者(P321)的雄激素受体基因，并在DNA结合域的第二个“锌指”中检测到核苷酸2006(G-C)的单核苷酸替换，导致615位的精氨酸残基转化为Pro残基。将这种突变引入雄激素受体基因，并将表达载体导入真核细胞，可以合成一种受体蛋白，该蛋白具有正常的结合动力学，但在受体活性的功能分析中不起作用。我们得出结论，雄激素受体DNA结合域中的替换突变是“受体阳性”雄激素抵抗的原因之一。
Androgen resistance is associated with a wide range of quantitative and qualitative defects in the androgen receptor. However, fibroblast cultures from approximately 10% of patients with the clinical, endocrine, and genetic features characteristic of androgen resistance express normal quantities of apparently normal androgen receptor in cultured genital skin fibroblasts (receptor-positive androgen resistance). We have analyzed the androgen receptor gene of one patient (P321) with receptor-positive, complete testicular feminization and detected a single nucleotide substitution at nucleotide 2006 (G----C) within the second "zinc finger" of the DNA-binding domain that results in the conversion of the arginine residue at position 615 into a proline residue. Introduction of this mutation into the androgen receptor cDNA and transfection of the expression plasmid into eukaryotic cells lead to the synthesis of a receptor protein that displays normal binding kinetics but is inactive in functional assays of receptor activity. We conclude that substitution mutations in the DNA-binding domain of the androgen receptor are one cause of "receptor-positive" androgen resistance.Images