title: Long-term biochemical evaluation of the androgen receptor pathway in males with disorders of sex development.
abstract: OBJECTIVE
  Disorders of sex (DSD) development represent a serious condition. Most of the underlying mechanisms remain unclear. Disturbances within the androgen receptor (AR) pathway frequently account for 46 XY-DSDs. The individual gender-related outcome often is unsatisfactory. We present a long-term AR gene-mutation-associated follow-up in a group of 46 XY-DSD patients.
  
  
  METHODS
  Twenty patients (46 XY) who underwent genitoplasty in infancy or early childhood were retrospectively identified. Median follow-up after surgery was 16 years. All were undervirilized at initial presentation. Thirteen had female gender assignment, and 7 were raised as males. A genital skin biopsy and subsequent fibroblast cultures were done. The specific binding of dihydrotestosterone, the thermostability of the receptor hormone complex, and 5-α-reductase activity were measured. AR gene mutations were detected by direct sequencing. The individual outcome was correlated with specific AR mutations.
  
  
  RESULTS
  AR point mutations were detected in 12, 7 were previously unknown. There was no specific androgen binding in 3, reduced affinity in 9, and normal binding in 8 patients. 5-α-Reductase activity was normal in 15, reduced in 4 and completely absent in 1 patient.
  
  
  CONCLUSIONS
  Retrospective evaluation revealed previously unknown and established AR gene mutations being associated with a distinct long-term outcome. Identification of the molecular mechanisms causing DSD will likely improve timely diagnosis and therapy. Exact characterization of AR activation and function may offer a treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome adding objective criteria for gender assignment in 46 XY-DSD patients.
authors.affiliation: Department of Pediatric Urology, Medical University Innsbruck, Innsbruck, Austria. christian.schwentner@i-med.ac.at
authors.forename: C
authors.initials: C
authors.lastname: Schwentner
authors.forename: J
authors.initials: J
authors.lastname: Czyz
authors.forename: J
authors.initials: J
authors.lastname: Seibold
authors.forename: T
authors.initials: T
authors.lastname: Todenhoefer
authors.forename: S H
authors.initials: SH
authors.lastname: Alloussi
authors.forename: H
authors.initials: H
authors.lastname: Klocker
authors.forename: G
authors.initials: G
authors.lastname: Gakis
authors.forename: A
authors.initials: A
authors.lastname: Stenzl
authors.forename: M
authors.initials: M
authors.lastname: Baka-Ostrowska
authors.forename: C
authors.initials: C
authors.lastname: Radmayr
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D012734:Disorders of Sex Development / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009154:Mutation; D011944:Receptors, Androgen / Q000235:genetics*; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D011944:Receptors, Androgen