Androgen receptor mutations associated with androgen insensitivity syndrome: a high content analysis approach leading to personalized medicine

PLoS One. 2009 Dec 9;4(12):e8179. doi: 10.1371/journal.pone.0008179.


Androgen insensitivity syndrome (AIS) is a rare disease associated with inactivating mutations of AR that disrupt male sexual differentiation, and cause a spectrum of phenotypic abnormalities having as a common denominator loss of reproductive viability. No established treatment exists for these conditions, however there are sporadic reports of patients (or recapitulated mutations in cell lines) that respond to administration of supraphysiologic doses (or pulses) of testosterone or synthetic ligands. Here, we utilize a novel high content analysis (HCA) approach to study AR function at the single cell level in genital skin fibroblasts (GSF). We discuss in detail findings in GSF from three historical patients with AIS, which include identification of novel mechanisms of AR malfunction, and the potential ability to utilize HCA for personalized treatment of patients affected by this condition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Substitution / genetics
  • Androgen-Insensitivity Syndrome / genetics*
  • Androgens
  • Cell Nucleus / metabolism
  • Dose-Response Relationship, Drug
  • Fibroblasts / metabolism
  • HeLa Cells
  • High-Throughput Screening Assays / methods*
  • Humans
  • Male
  • Mutant Proteins / metabolism
  • Mutation / genetics*
  • Precision Medicine / methods*
  • Protein Structure, Tertiary
  • Protein Transport
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / genetics*
  • Transcription, Genetic


  • AR protein, human
  • Androgens
  • Mutant Proteins
  • Receptors, Androgen