title: Novel amino acid substitutional mutation, tyrosine-739-aspartic acid, in the androgen receptor gene in complete androgen insensitivity syndrome.
abstract: Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder. The molecular mechanism of AIS is reduction or absence of androgen signalling caused by androgen receptor (AR) malfunction or absence. The phenotype of AIS varies from a complete female phenotype (complete AIS, CAIS) to male genitalia with mild hypospadias (partial AIS, PAIS). In the current study, we characterize a novel point mutation in the ligand binding domain of the AR gene in a 50-year-old Japanese CAIS patient. Sequence analysis showed a single point mutation at nucleotide 3359 (Genbank, NM 000044), T to C, in exon E in the AR gene. This mutation led to the conversion of codon 739 tyrosine into aspartic acid in the ligand binding domain. No specific androgen binding was detected in genital fibroblasts isolated from the patient. Transcriptional activating activity of the mutant AR was examined by transient DNA transfection into COS-1 cells. Wild-type AR successfully activated androgen inducible MMTV promoter dose-dependently. In contrast, the mutant AR did not activate MMTV promoter. Thus, we demonstrated the molecular characteristics of the novel point mutation in the ligand binding domain of the AR gene associated with CAIS. This information will provide a further understanding of the structure and function of the AR gene.
authors.affiliation: Department of Urology, Gunma University School of Medicine, Maebashi, Gunma, Japan. kazu@showa.gunma-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Fukabori
authors.forename: H
authors.initials: H
authors.lastname: Nakazato
authors.forename: M
authors.initials: M
authors.lastname: Hasumi
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Kurokawa
authors.forename: H
authors.initials: H
authors.lastname: Yamanaka
mesh_terms: D019943:Amino Acid Substitution; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009277:Nandrolone / Q000031:analogs & derivatives / Q000737:chemistry; D017354:Point Mutation / Q000235:genetics* / Q000502:physiology; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood; D014162:Transfection
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone; C013915:boldenone; D012313:RNA; D009277:Nandrolone; C100075:mibolerone