Lobaccaro J M, Belon C, Chaussain J L, Job J C, Toublanc J E, Battin J, Rochiccioli P, Bernasconi S, Bost M, Bozzola M
Unité de Biochimie Endocrinienne du Développement et de la Reproduction, Hôpital Lapeyronie, Montpellier, France.
Horm Res. 1992;37(1-2):54-9. doi: 10.1159/000182282.
In patients with androgen insensitivity syndrome (AIS), RFLP study of the androgen receptor gene made it possible to analyze whether deletions or mutations could be responsible for abnormalities in androgen responsiveness. We studied RFLPs of DNA from 25 46,XY patients with partial AIS (PAIS), defined as a concentration of androgen receptor in genital-skin fibroblasts less than 340 fmol/mg DNA, and DNA from 27 46,XY patients with complete AIS (CAIS) with no detectable androgen receptor site. DNA samples were digested with BamHI, EcoRI, HindIII and TaqI restriction enzymes and hybridized with three cDNA probes covering the three domains of the androgen receptor. When we had the maternal and an unaffected brother's DNA, we analyzed the two androgen receptor gene polymorphisms described, the HindIII and the exon 1 CAG repeat polymorphisms, in order to distinguish the two maternal X chromosomes, and to detect carriers of AIS. We did not find any large deletion among the 52 patients. We observed a heterozygous mother in 3 of 14 families studied with the HindIII polymorphism, and in 12 of 25 families using the exon 1 CAG repeat polymorphism. This study suggests that in AIS, abnormalities in androgen receptor response could be related to point mutations or microdeletions rather than to gross structural alterations of the androgen receptor gene. Furthermore, unless the point mutation has been described, exon 1 and HindIII polymorphism studies would enable the identification of carriers in 50% of families, and the prenatal diagnosis of AIS.
在雄激素不敏感综合征（AIS）患者中，对雄激素受体基因进行限制性片段长度多态性（RFLP）研究，使得分析缺失或突变是否可能导致雄激素反应异常成为可能。我们研究了25例46,XY型部分性雄激素不敏感综合征（PAIS）患者（定义为生殖器皮肤成纤维细胞中雄激素受体浓度低于340 fmol/mg DNA）以及27例46,XY型完全性雄激素不敏感综合征（CAIS）患者（未检测到雄激素受体位点）的DNA的RFLP。DNA样本用BamHI、EcoRI、HindIII和TaqI限制性内切酶消化，并与覆盖雄激素受体三个结构域的三种cDNA探针杂交。当我们获得母亲和未受影响兄弟的DNA时，我们分析了所描述的两种雄激素受体基因多态性，即HindIII和外显子1 CAG重复多态性，以区分两条母亲的X染色体，并检测AIS携带者。我们在52例患者中未发现任何大片段缺失。在用HindIII多态性研究的14个家族中的3个以及用外显子1 CAG重复多态性研究的25个家族中的12个中，我们观察到杂合子母亲。这项研究表明，在AIS中，雄激素受体反应异常可能与点突变或微缺失有关，而不是与雄激素受体基因的总体结构改变有关。此外，除非已经描述了点突变，外显子1和HindIII多态性研究将能够在50%的家族中识别携带者，并进行AIS的产前诊断。
