title: Androgen receptor mutations.
abstract: Male sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. At least three pathological situations are associated with abnormal androgen receptor structure and function: androgen insensitivity syndrome (AIS), spinal and bulbar muscular atrophy (SBMA) and prostate cancer. In the X-linked androgen insensitivity syndrome, defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. Complete or gross deletions of the androgen receptor gene have not been found frequently in persons with complete androgen insensitivity syndrome. Point mutations at several different sites in exons 2-8 encoding the DNA- and androgen-binding domain, have been reported for partial and complete forms of androgen insensitivity. A relatively high number of mutations were reported in two different clusters in exon 5 and in exon 7. The number of mutations in exon 1 is extremely low and no mutations have been reported in the hinge region, located between the DNA-binding domain and the ligand-binding domain and which is encoded by the first half of exon 4. Androgen receptor gene mutations in prostate cancer are very rare and are reported only in exons 4-8. The X-linked spinal and bulbar muscle atrophy (SBMA; Kennedy's disease) is associated with an expanded length (> 40 residues) of one of the polyglutamine stretches in the N-terminal domain of the androgen receptor.
authors.affiliation: Department of Endocrinology, Erasmus University, Rotterdam, The Netherlands.
authors.forename: A O
authors.initials: AO
authors.lastname: Brinkmann
authors.forename: G
authors.initials: G
authors.lastname: Jenster
authors.forename: C
authors.initials: C
authors.lastname: Ris-Stalpers
authors.forename: J A
authors.initials: JA
authors.lastname: van der Korput
authors.forename: H T
authors.initials: HT
authors.lastname: Brüggenwirth
authors.forename: A L
authors.initials: AL
authors.lastname: Boehmer
authors.forename: J
authors.initials: J
authors.lastname: Trapman
mesh_terms: D000595:Amino Acid Sequence; D000728:Androgens / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000503:physiopathology*; D017354:Point Mutation; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000235:genetics*; D013577:Syndrome
chemical_list: D000728:Androgens; D004268:DNA-Binding Proteins; D011944:Receptors, Androgen