Shortage of glutamine (CAG) homopolymeric repeats suppresses the expression of the androgen receptor in familial cases with complete androgen insensitivity syndrome.

The androgen receptor gene of two familial cases with complete androgen insensitivity syndrome was analyzed. The shortage of glutamine homopolymeric repeats (13 repeats) in the N-terminal domain of the androgen receptor of the patients was identified by DNA sequence analysis. In vitro transfection experiments with the patients' androgen receptor gene indicated that the expression of the androgen receptor in transfected COS-7 cells was decreased by 10% as compared to that of the wild type androgen receptor gene. The thermal stability of the 5 alpha-dihydrotestosterone-androgen receptor complex was also partially impaired. The capacity of the androgen receptor to activate target gene transcription was partially disturbed in a luciferase assay. The shortened glutamine homopolymeric repeats might therefore be related to the pathogenesis of complete androgen insensitivity syndrome.