人类雄激素不敏感是由于在雄激素受体类固醇结合域编码氨基酸替换的点突变。
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Murono K, Mendonca BB, Arnhold IJ, Rigon AC, Migeon CJ, Brown TR
人类雄激素不敏感是由于在雄激素受体类固醇结合域编码氨基酸替换的点突变。
胡姆Mutat. 1995;6(2):152-62。
- PubMed ID
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7581399 (查看PubMed］
- 摘要
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在来自四个雄激素不敏感综合征家族的五名受试者中发现了人类雄激素受体基因突变。通过聚合酶链式反应从基因组DNA中扩增雄激素受体基因的单个外显子，并通过变性梯度凝胶电泳筛选其熔解特性的序列依赖性差异。对迁移率改变的外显子的DNA片段进行测序。在编码雄激素受体的类固醇结合域的外显子5、6和7中发现了四种不同的单核苷酸基取代。在一名生殖器模糊的受试者中，氨基酸残基763由酪氨酸变为半胱氨酸(TAC—>TGC;Y763C)。四名受试者，包括两名兄弟姐妹，完全雄激素不敏感。在一名受试者中，残留779从精氨酸变为色氨酸(CGC—>TGG;R779W)，另一个实验对象(M807V)在807位发生缬氨酸(GTG)取代蛋氨酸(ATG)残基，两个兄弟姐妹(R855C)在残基855发生突变，将精氨酸(CGC)转变为半胱氨酸(TGC)。突变受体Y763C与合成雄激素配体甲基三烯醇酮(R1881)的结合比正常受体减少54%。 Transcriptional activation of a mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) reporter gene by AR mutant Y763C was negligible at 0.1 nM R1881 and only 55% at 10 nM R1881 when compared to the maximal response with the normal AR, as assessed by CAT activity. Mutant M807V retained only 22% of normal R1881 binding and mutant R855C was unable to bind the steroid. In accordance with the steroid binding, transcriptional activation of MMTV-CAT by M807V rose to only 26% of control in the presence of 10 nM R1881, a concentration at which R855C remained functionally inactive. In summary, missense mutations within the exons of the androgen receptor gene encoding the steroid-binding domain of the receptor are common causes of both partial and complete forms of androgen insensitivity syndrome.