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. 1991 Mar;87(3):1123–1126. doi: 10.1172/JCI115076

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 1, S Zoppi 1, P B Grino 1, J E Griffin 1, J D Wilson 1, M J McPhaul 1
PMCID: PMC329911  PMID: 1999491

Abstract

Androgen resistance is associated with a wide range of quantitative and qualitative defects in the androgen receptor. However, fibroblast cultures from approximately 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.

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Selected References

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