Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9703
Title: Novel androgen receptor gene mutations in Australian patients with complete androgen insensitivity syndrome.
Authors: MacLean, Helen E;Ball, Emma M A;Rekaris, Georgia;Warne, Garry L;Zajac, Jeffrey D
Affiliation: Department of Medicine (AH/NH), University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia. hmaclean@unimelb.edu.au
Issue Date: 1-Mar-2004
Citation: Human Mutation; 23(3): 287
Abstract: We have identified androgen receptor (AR) gene mutations in eight Australian subjects with complete androgen insensitivity syndrome (AIS). Four individuals, from three families, have novel mutations that introduce premature termination codons. Two siblings have the nonsense mutation Glu681X, and another subject has the nonsense mutation p.Ser884X. The other subject has a CA insertion at codon 829 (c.2847_2848insCA), causing a frameshift mutation that introduces four nonsense amino acids prior to a Stop codon. All the termination codons occur in the ligand binding domain, and cause reduced androgen binding in patient genital skin fibroblasts. Four further patients have missense mutations. One subject has two different mutations, p.Ala645Asp in the hinge region of the receptor, and p.Arg752Gln in the ligand binding domain. Both these mutations have previously been reported in patients with AIS, but the combination of these two mutations in one subject is unique. Another subject has a novel c.2533G>C transversion at the first nucleotide in exon 5, introducing the amino acid change p.Gly724Ala at a highly conserved residue in the ligand binding domain. Androgen binding is normal in fibroblasts from this subject, although other point mutations at this amino acid totally abolish binding. Two other subjects have mutations previously described as causing AIS, namely p.Arg779Trp and p.Val889Met substitutions in the ligand binding domain of the receptor. The p.Arg779Trp mutation is associated with the detection of a truncated AR protein in this patient's fibroblasts, suggesting the mutation renders the receptor susceptible to proteolysis.
Internal ID Number: 14974091
URI: http://ahro.austin.org.au/austinjspui/handle/1/9703
DOI: 10.1002/humu.9221
URL: http://www.ncbi.nlm.nih.gov/pubmed/14974091
Type: Journal Article
Subjects: Adult
Androgen-Insensitivity Syndrome.genetics
Australia
Child
Child, Preschool
Codon, Nonsense.genetics
Codon, Terminator.genetics
Female
Frameshift Mutation.genetics
Gonadal Dysgenesis, 46,XY.genetics
Humans
Male
Mutation.genetics
Receptors, Androgen.genetics
Appears in Collections:Journal articles

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