title: Complete androgen insensitivity syndrome due to a new frameshift deletion in exon 4 of the androgen receptor gene: functional analysis of the mutant receptor.
abstract: We studied the androgen receptor gene in a large kindred with complete androgen insensitivity syndrome and negative receptor-binding activity, single-strand conformation polymorphism (SSCP) analysis and sequencing identified a 13 base pair deletion within exon 4. This was responsible for a predictive frameshift in the open reading frame and introduction of a premature stop codon at position 783 instead of 919. The deletion was reproduced in androgen receptor wildtype cDNA and transfected into mammalian cells. Western blot showed a smaller androgen receptor of 94 kDa for the transfected mutated cDNA instead of 110 kDa. Androgen-binding assay of the mutated transfected cells assessed the lack of androgen-binding. Gel retardation assay demonstrated the ability of the mutant to bind target DNA; however, the mutant was unable to transactivate a reporter gene. Although the role of the partial deletion in the lack of androgen action was expected, in vitro analyses highlight the role of the abnormal C-terminal portion in the inhibition of the receptor transregulatory activity of the protein causing androgen resistance in this family.
authors.affiliation: Centre de Recherches de l'Institut National de la Santé et de la Recherche Médicale, INSERM, Montpellier, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Lobaccaro
authors.forename: S
authors.initials: S
authors.lastname: Lumbroso
authors.forename: N
authors.initials: N
authors.lastname: Poujol
authors.forename: V
authors.initials: V
authors.lastname: Georget
authors.forename: A O
authors.initials: AO
authors.lastname: Brinkmann
authors.forename: G
authors.initials: G
authors.lastname: Malpuech
authors.forename: C
authors.initials: C
authors.lastname: Sultan
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D004351:Drug Resistance; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D005602:France; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014444:Tyrosine Transaminase / Q000235:genetics
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D004247:DNA; D014444:Tyrosine Transaminase