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Novel androgen receptor gene mutations in Australian patients with complete androgen insensitivity syndrome.
Hum Mutat. 2004 Mar; 23(3):287.HM

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.

Authors+Show Affiliations

Department of Medicine (AH/NH), University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia. hmaclean@unimelb.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14974091

Citation

MacLean, Helen E., et al. "Novel Androgen Receptor Gene Mutations in Australian Patients With Complete Androgen Insensitivity Syndrome." Human Mutation, vol. 23, no. 3, 2004, p. 287.
MacLean HE, Ball EM, Rekaris G, et al. Novel androgen receptor gene mutations in Australian patients with complete androgen insensitivity syndrome. Hum Mutat. 2004;23(3):287.
MacLean, H. E., Ball, E. M., Rekaris, G., Warne, G. L., & Zajac, J. D. (2004). Novel androgen receptor gene mutations in Australian patients with complete androgen insensitivity syndrome. Human Mutation, 23(3), 287.
MacLean HE, et al. Novel Androgen Receptor Gene Mutations in Australian Patients With Complete Androgen Insensitivity Syndrome. Hum Mutat. 2004;23(3):287. PubMed PMID: 14974091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel androgen receptor gene mutations in Australian patients with complete androgen insensitivity syndrome. AU - MacLean,Helen E, AU - Ball,Emma M A, AU - Rekaris,Georgia, AU - Warne,Garry L, AU - Zajac,Jeffrey D, PY - 2004/2/20/pubmed PY - 2004/3/26/medline PY - 2004/2/20/entrez SP - 287 EP - 287 JF - Human mutation JO - Hum Mutat VL - 23 IS - 3 N2 - 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. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/14974091/Novel_androgen_receptor_gene_mutations_in_Australian_patients_with_complete_androgen_insensitivity_syndrome_ L2 - https://doi.org/10.1002/humu.9221 DB - PRIME DP - Unbound Medicine ER -