title: Androgen receptor mutations associated with androgen insensitivity syndrome: a high content analysis approach leading to personalized medicine.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Szafran
authors.forename: Sean
authors.initials: S
authors.lastname: Hartig
authors.forename: Huiying
authors.initials: H
authors.lastname: Sun
authors.forename: Ivan P
authors.initials: IP
authors.lastname: Uray
authors.forename: Maria
authors.initials: M
authors.lastname: Szwarc
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Shen
authors.forename: Sanjay N
authors.initials: SN
authors.lastname: Mediwala
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bell
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McPhaul
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mancini
authors.forename: Marco
authors.initials: M
authors.lastname: Marcelli
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D000728:Androgens; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008297:Male; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D057285:Precision Medicine / Q000379:methods*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C410798:AR protein, human; D000728:Androgens; D050505:Mutant Proteins; D011944:Receptors, Androgen