Wide variation in androgen receptor dysfunction in complete androgen insensitivity syndrome

  • Bevan C
  • Hughes I
  • Patterson M
  • 2

    Readers

    Mendeley users who have this article in their library.
  • 21

    Citations

    Citations of this article.

Abstract

Androgen insensitivity syndrome (AIS) is a disorder of male sexual differentiation caused by mutations in the androgen receptor (AR) gene. The partial form (PAIS), associated with varying degrees of receptor dysfunction, presents with a range of undervirilization phenotypes. The complete form (CAIS) is characterized by normal female external appearance at birth. In these cases the receptor is often absent or inactive. However, cases have been described where the mutant receptor concerned has considerable residual activity in in vitro assays. Here we describe the effects of five mutations, Gly750Asp, Leu762Phe, Ala765Thr, Asp864Asn and Leu907Phe, identified in complete androgen insensitivity patients. In vitro assays of mutant androgen receptors expressed in a mammalian cell line showed that the Gly750Asp, Leu762Phe and Ala765Thr mutations cause almost complete loss of androgen-binding activity, suggesting that these residues are critical for ligand binding. However, receptors with Asp864Asn and Leu907Phe, although defective, were capable of considerable binding and transactivation activity. Given that some mutations identified in PAIS patients have a more severe effect on androgen receptor function than two CAIS mutations described here, these results provide further evidence that other factors, including genetic background, can have a significant impact on the phenotype associated with a particular AR mutation.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Charlotte L. Bevan

  • Ieuan A. Hughes

  • Mark N. Patterson

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free