title: Amber mutation creates a diagnostic MaeI site in the androgen receptor gene of a family with complete androgen insensitivity.
abstract: We have discovered in the X-linked androgen receptor gene a single nucleotide substitution that is the putative cause of complete androgen insensitivity (resistance) in a family with affected individuals in 2 generations. Earlier studies on the family indicated co-segregation of mutant phenotype and the RFLPs at the loci DXS1 and DXYS1. The mutation is an adenine-to-thymine transversion in exon 8 that changes the sense of codon 882 from lysine to an amber (UAG) translation termination signal. The substitution creates a recognition sequence for the restriction endonuclease MaeI: this permits ready recognition of hemizygotes and heterozygotes after amplification of genomic exon 8 by the polymerase chain reaction. The mutation predicts the synthesis of a truncated receptor that lacks 36 amino acids at the carboxy terminus of its 252-amino acid androgen-binding domain. The cultured genital skin fibroblasts of the one affected patient examined have normal levels of androgen receptor mRNA, but negligible androgen-receptor binding activity. These results accord with a variety of data from spontaneous and artificial mutations indicating that all portions of the steroid binding domain contribute to normal steroid binding by a steroid receptor.
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Trifiro
authors.forename: R L
authors.initials: RL
authors.lastname: Prior
authors.forename: N
authors.initials: N
authors.lastname: Sabbaghian
authors.forename: L
authors.initials: L
authors.lastname: Pinsky
authors.forename: M
authors.initials: M
authors.lastname: Kaufman
authors.forename: E G
authors.initials: EG
authors.lastname: Nylen
authors.forename: D D
authors.initials: DD
authors.lastname: Belsham
authors.forename: C R
authors.initials: CR
authors.lastname: Greenberg
authors.forename: K
authors.initials: K
authors.lastname: Wrogemann
mesh_terms: D000595:Amino Acid Sequence; D000728:Androgens / Q000378:metabolism*; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D004247:DNA / Q000302:isolation & purification; D005091:Exons / Q000502:physiology; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000235:genetics*; D012313:RNA / Q000302:isolation & purification; D011944:Receptors, Androgen / Q000235:genetics*; D014960:X Chromosome
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D012313:RNA; D004247:DNA