An androgen receptor mutation in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core is associated with complete androgen insensitivity
I. Peters et al., An androgen receptor mutation in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core is associated with complete androgen insensitivity, MOL C ENDOC, 148(1-2), 1999, pp. 47-53
Subjects with androgen insensitivity syndromes (AIS) are characterized by a
46, XY karyotype, presence of testes, normal or elevated androgen levels i
n blood, and impairment of the usual response to androgens associated with
various abberrations of male differentiation and virilization ranging from
slightly undervirilized men to phenotypic females. Here we describe a novel
proline to serine mutation in codon 892 (exon 8) of the androgen receptor
in a patient with complete androgen insensitivity. The mutation is located
in the direct vicinity of the proposed C-terminal alpha-helix of the ligand
binding domain containing the AF-2 transcriptional activating function cor
e. Investigation of androgen binding in cultured testicular fibroblasts of
the patient revealed a reduced AR binding capacity (11 fmol/mg protein) and
a highly elevated K-d value (3.1 nM) in comparison to control genital skin
fibroblasts. Cotransfection studies with an androgen-responsive reporter g
ene revealed a diminished transactivation property of the mutant androgen r
eceptor. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.