Analysis of the androgen receptor gene in cases with intersex, and a trial of early diagnosis and treatment of intersex.

本文报道了3例XX男性尿道下裂、1例真两性畸形、3例混合性性腺发育不全、10例尿道下裂合并前列腺囊增大、5例Reinfenstein综合征和4例睾丸女性化综合征患者的生殖器皮肤成纤维细胞中雄激素受体(AR)的热稳定性。对4例Reinfenstein综合征和1例混合性性腺发育不全患者的雄激素受体基因进行了除外显子A外显子测序。外显子D(密码子709，G*A)的一个点突变在两个兄弟、他们的母亲、一个表亲、他的母亲和他们的祖母中被发现。这一点突变导致了谷氨酰胺向赖氨酸的氨基酸交换。在另一例Reinfenstein综合征患者中，发现G外显子的一个点突变(密码子826，T*A)，导致苯丙氨酸到酪氨酸的氨基酸交换。由于AR激素结合域的点突变导致的氨基酸交换似乎在结合部位产生了亲水环境，这可能是这些情况下雄激素受体耐热性的主要原因。对1例混合性性腺发育不全患者的AR基因进行了测序，发现外显子B有一个点突变(密码子539，G*A)。DNA结合域的这种点突变可能会给转录后处理带来一些问题。目前正在对上述双性患者进行AR基因测序，以期用一张生殖器皮肤的聚合酶链式反应方法诊断出具有不耐热雄激素受体的双性状态患者，并尽早进行治疗。

Thermolability of the androgen receptor (AR) was demonstrated in fibroblasts cultured from genital skin in the cases with intersex (3 XX male with hypospadias, 1 true hermaphroditism, 3 mixed gonadal dysgenesis, 10 hypospadias with enlarged prostatic utricle, 5 Reinfenstein syndrome, and 4 testicular feminization syndrome). The androgen receptor gene except exon A was sequenced in 4 Reinfenstein syndrome, and 1 mixed gonadal dysgenesis. One point mutation in exon D (codon 709, G*A) was found in two brothers, their mother, one cousin, his mother, and their grand mother. This point mutation brought the amino acid exchange from glutamine to lysine. In another case of Reinfenstein syndrome one point mutation in exon G (codon 826, T*A) was identified, which caused amino acid exchange from phenylalanine to tyrosine. Both amino acid exchange due to point mutation in the hormone binding domain of AR seems to generate hydrophillic environment in the binding site which might be a major reason of thermolability of androgen receptorin these cases. The AR gene of a case with mixed gonadal dysgenesis was also sequenced that revealed one point mutation in exon B (codon 539, G*A). This point mutation in the DNA binding domain might cause some problems on the post-transcriptional processing. It is in the process of the AR gene sequencing of cases with intersex above mentioned, and expected to diagnose patients with intersex state having thermolabile androgen receptor using PCR method about a piece of genital skin, and treat cases as early as possible.