A mutation in the DNA-binding domain of the androgen receptor gene causes complete testicular feminization in a patient with receptor-positive androgen resistance

M. Marcelli, S. Zoppi, P. B. Grino, Jim Griffin III, J. D. Wilson, M. J. McPhaul

Research output: Contribution to journalArticle

68 Scopus citations


Androgen resistance is associated with a wide range of quantitative and qualitative defects in the androgen receptor. However, fibroblast cultures from ∼ 10% of patients with the clinical, endocrine, and genetic features characteristic of androgen resistance express normal quantities of apparently normal androgen receptor in cultured genital skin fibroblasts (receptor-positive androgen resistance). We have analyzed the androgen receptor gene of one patient (P321) with receptor-positive, complete testicular feminization and detected a single nucleotide substitution at nucleotide 2006 (G → C) within the second "zinc finger" of the DNA-binding domain that results in the conversion of the arginine residue at position 615 into a proline residue. Introduction of this mutation into the androgen receptor cDNA and transfection of the expression plasmid into eukaryotic cells lead to the synthesis of a receptor protein that displays normal binding kinetics but is inactive in functional assays of receptor activity. We conclude that substitution mutations in the DNA-binding domain of the androgen receptor are one cause of "receptor-positive" androgen resistance.

Original languageEnglish (US)
Pages (from-to)1123-1126
Number of pages4
JournalJournal of Clinical Investigation
Issue number3
StatePublished - Jan 1 1991



  • "zinc-finger"
  • Steroid receptor
  • Substitution mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this