title: A single-base substitution in exon 6 of the androgen receptor gene causing complete androgen insensitivity: the mutated receptor fails to transactivate but binds to DNA in vitro.
abstract: A single-base substitution in the coding region of the androgen receptor (AR) gene caused complete androgen insensitivity in a patient with 46,XY karyotype. The mutation was a T-to-G transition in exon 6 and changed the codon 807 from ATG (methionine) to AGG (arginine) in the hormone-binding domain of the protein. The mutation was inserted into the wild-type human AR cDNA and the resulting cDNA expressed in CV-1 cells. Native and mutated AR proteins synthesized in recipient cells had identical molecular masses. Ligand-binding activity of the mutant receptor was less than 5% of that of the wild-type AR. The mutant's interaction with an androgen-response element in vitro was identical to that of the native aporeceptor; however, it did not transactivate a reporter gene construct in transfected CV-1 cells. Androgen insensitivity in our patient was thus due to altered structure of the receptor's steroid-binding region, which prevented the mutated AR from gaining a transcriptionally active form in vivo.
authors.affiliation: Population Council, New York, NY.
authors.forename: O
authors.initials: O
authors.lastname: Adeyemo
authors.forename: P J
authors.initials: PJ
authors.lastname: Kallio
authors.forename: J J
authors.initials: JJ
authors.lastname: Palvimo
authors.forename: K
authors.initials: K
authors.lastname: Kontula
authors.forename: O A
authors.initials: OA
authors.lastname: Jänne
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012734:Disorders of Sex Development / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008715:Methionine; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D003062:Codon; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D001120:Arginine; D008715:Methionine