Imperato-McGinley J, Ip N Y, Gautier T, Neuweiler J, Gruenspan H, Liao S, Chang C, Balazs I
Department of Medicine, Cornell University Medical Center, New York, New York 10021.
Am J Med Genet. 1990 May;36(1):104-8. doi: 10.1002/ajmg.1320360121.
DNA linkage analysis of the X chromosome and studies with cDNA probes specific for the androgen receptor gene were performed on the largest known kindred with the syndrome of complete androgen insensitivity. The affected subjects (XY) have absent binding of dihydrotestosterone to the androgen receptor (the receptor negative form of androgen insensitivity). In this kindred there was maternal transmission of the gene, with all affected males expressing complete genital feminization. Linkage analysis studies were conducted with two DNA probes, DXS1 and PGK1, localized to the Xq11-Xq13 region of the long arm of the X chromosome near the centromere. The results demonstrate linkage to the markers in the order of DXS1-(AR; PGK1), thus localizing the AR gene to an area between Xq11 and Xq13. Three cDNA probes that span various parts of the androgen receptor gene, including the DNA and steroid binding domain, were used to evaluate the androgen receptor gene in normal individuals, carrier mothers, and affected subjects. Identical restriction fragment patterns were found in all three groups studied. Thus the androgen receptor gene was present in affected subjects without detectable DNA polymorphism at the androgen binding domain. Therefore, despite complete absence of binding to the androgen receptor, the defect in the androgen receptor gene in this kindred is not the result of a gene deletion. The results point to a mutation or a small insertion/deletion as the probable cause of the syndrome.
对已知最大的完全雄激素不敏感综合征家系进行了X染色体的DNA连锁分析，并使用雄激素受体基因特异性的cDNA探针进行研究。受影响的个体（XY）中，二氢睾酮与雄激素受体的结合缺失（雄激素不敏感的受体阴性形式）。在这个家系中，该基因由母亲传递，所有受影响的男性都表现出完全的生殖器女性化。使用定位在X染色体长臂靠近着丝粒的Xq11-Xq13区域的两个DNA探针DXS1和PGK1进行连锁分析研究。结果表明与标记的连锁顺序为DXS1-(AR; PGK1)，从而将AR基因定位到Xq11和Xq13之间的区域。使用跨越雄激素受体基因不同部分（包括DNA和类固醇结合结构域）的三个cDNA探针来评估正常个体、携带者母亲和受影响个体中的雄激素受体基因。在所有研究的三组中发现了相同的限制性片段模式。因此，在受影响个体中存在雄激素受体基因，在雄激素结合结构域没有可检测到的DNA多态性。因此，尽管完全不存在与雄激素受体的结合，但这个家系中雄激素受体基因的缺陷不是基因缺失的结果。结果表明，突变或小的插入/缺失可能是该综合征的病因。
