Androgen Receptor Mutations Associated with Androgen Insensitivity Syndrome: a High Content Analysis Approach Leading to Personalized Medicine

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Dec 17

PMID 20011049

Citations 12

Authors

Adam T Szafran

Sean Hartig

Huiying Sun

Ivan P Uray

Maria Szwarc

Yuqing Shen

Sanjay N Mediwala

Jennifer Bell

Michael J McPhaul

Michael A Mancini

Marco Marcelli

Affiliations

Soon will be listed here.

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.

Citing Articles

Advances in the understanding of androgen receptor structure and function and in the development of next-generation AR-targeted therapeutics.

Effah W, Khalil M, Hwang D, Miller D, Narayanan R Steroids. 2024; 210:109486.

PMID: 39111362 PMC: 11380798. DOI: 10.1016/j.steroids.2024.109486.

Single-Cell Distribution Analysis of AR Levels by High-Throughput Microscopy in Cell Models: Application for Testing Endocrine-Disrupting Chemicals.

Stossi F, Mistry R, Singh P, Johnson H, Mancini M, Szafran A SLAS Discov. 2020; 25(7):684-694.

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A Mechanistic High-Content Analysis Assay Using a Chimeric Androgen Receptor That Rapidly Characterizes Androgenic Chemicals.

Szafran A, Bolt M, Obkirchner C, Mancini M, Helsen C, Claessens F SLAS Discov. 2020; 25(7):695-708.

PMID: 32392092 PMC: 7477889. DOI: 10.1177/2472555220922917.

High-content drug screening for rare diseases.

Bellomo F, Medina D, De Leo E, Panarella A, Emma F J Inherit Metab Dis. 2017; 40(4):601-607.

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A practical guide for evaluating gonadal germ cell tumor predisposition in differences of sex development.

Pyle L, Nathanson K Am J Med Genet C Semin Med Genet. 2017; 175(2):304-314.

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