GENETIC-BASIS OF ENDOCRINE DISEASE .4. THE SPECTRUM OF MUTATIONS IN THE ANDROGEN RECEPTOR GENE THAT CAUSES ANDROGEN RESISTANCE
GENETIC-BASIS OF ENDOCRINE DISEASE .4. THE SPECTRUM OF MUTATIONS IN THE ANDROGEN RECEPTOR GENE THAT CAUSES ANDROGEN RESISTANCE
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DOI：
10.1210/jc.76.1.17
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发表时间：
1993-01-01
影响因子：
5.8
通讯作者：
WILSON, JD
中科院分区：
文献类型：
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作者：
MCPHAUL, MJ;MARCELLI, M;WILSON, JD
雄激素受体基因的突变会导致男性性发育的表型异常，范围从女性表型(完全睾丸女性化)到男性化程度不足或不育的男性。我们利用分子生物学的工具，分析了31例雄激素抵抗综合征无关受试者的雄激素受体基因突变。大多数缺陷是由于核苷酸变化引起的提前终止密码子或编码雄激素受体的开放阅读框内的单个氨基酸替换，这些替换大多定位于雄激素受体的三个区域：DNA结合域和雄激素结合域的两个片段。较少的情况下，基因部分或完全缺失已被发现。对雄激素抵抗患者雄激素受体的功能研究和免疫印迹分析表明，在大多数情况下，表型异常是受体功能受损或受体丰度降低或两者兼而有之的结果。
Mutations in the androgen receptor gene cause phenotypic abnormalities of male sexual development that range from a female phenotype (complete testicular feminization) to that of undervirilized or infertile men. Using the tools of molecular biology, we have analyzed androgen receptor gene mutations in 31 unrelated subjects with androgen resistance syndromes. Most of the defects are due to nucleotide changes that cause premature termination codons or single amino acid substitutions within the open reading frame encoding the androgen receptor, and the majority of these substitutions are localized in three regions of the androgen receptor: the DNA-binding domain and two segments of the androgen-binding domain. Less frequently, partial or complete gene deletions have been identified. Functional studies and immunoblot assays of the androgen receptors in patients with androgen resistance indicate that in most cases the phenotypic abnormalities are the result of impairment of receptor function or decreases in receptor abundance or both.