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

本文报道了间性者（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例尿道下裂伴前列腺椭圆囊增大，5例Reinfenstein综合征，4例睾丸女性化综合征）生殖器皮肤成纤维细胞雄激素受体（AR）的热不稳定性。对4例Reinfenstein综合征和1例混合性性腺发育不全的雄激素受体基因进行了测序。外显子D（密码子709，G*A）的一个点突变被发现在两个兄弟，他们的母亲，一个堂兄弟，他的母亲，和他们的祖母。这种点突变导致氨基酸从谷氨酰胺交换为赖氨酸。在另一例Reinfenstein综合征中，发现外显子G（密码子826，T*A）的一个点突变，导致氨基酸从苯丙氨酸转换为酪氨酸。这两种氨基酸的交换都是由于AR激素结合区的点突变引起的，结合位点可能产生了一种热环境，这可能是雄激素受体热不稳定性的主要原因。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）。这种DNA结合区的点突变可能会导致转录后加工的一些问题。目前正在对上述双性患者进行AR基因测序，以期通过PCR方法对生殖器皮肤标本进行热不稳定性雄激素受体检测，诊断双性状态患者，并尽早治疗。

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.