Batch J A, Williams D M, Davies H R, Brown B D, Evans B A, Hughes I A, Patterson M N
Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, UK.
Hum Mol Genet. 1992 Oct;1(7):497-503. doi: 10.1093/hmg/1.7.497.
The androgen insensitivity syndrome (AIS) is a disorder of male sexual development resulting in a wide range of clinical phenotypes. AIS is classified into two phenotypic forms: complete (CAIS) and partial (PAIS). To determine the molecular basis of the phenotypic diversity in AIS, we have studied 27 subjects (13 CAIS, 14 PAIS), spanning the full range of AIS phenotypes. We report the results of a mutation screen of the androgen receptor gene. The coding regions of the gene were amplified by the polymerase chain reaction and screened for single strand conformation polymorphisms to identify mutations. This was followed by DNA sequencing of putative mutant segments. Androgen receptor gene mutations were identified in nine CAIS and five PAIS subjects. Two of the CAIS mutations in exon A resulted in frameshifts. A third CAIS mutation resulted in the deletion of a single amino acid from the ligand binding domain of the receptor. All other mutations caused single amino acid substitutions in the ligand binding domain. These results suggest that mutations affecting the ligand binding domain of the androgen receptor are the most frequent cause of AIS, although some cases of PAIS may be the result of other, as yet undefined, genetic lesions.
雄激素不敏感综合征（AIS）是一种男性性发育障碍，会导致多种临床表型。AIS分为两种表型形式：完全型（CAIS）和部分型（PAIS）。为了确定AIS表型多样性的分子基础，我们研究了27名受试者（13名CAIS，14名PAIS），涵盖了AIS的全部表型范围。我们报告了雄激素受体基因突变筛查的结果。该基因的编码区通过聚合酶链反应进行扩增，并筛查单链构象多态性以鉴定突变。随后对推定的突变片段进行DNA测序。在9名CAIS和5名PAIS受试者中鉴定出雄激素受体基因突变。外显子A中的两个CAIS突变导致移码。第三个CAIS突变导致受体配体结合域缺失一个氨基酸。所有其他突变导致配体结合域中的单氨基酸替换。这些结果表明，影响雄激素受体配体结合域的突变是AIS最常见的原因，尽管一些PAIS病例可能是其他尚未明确的遗传损伤的结果。
