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

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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.