Novel molecular defects in the androgen receptor gene of Mexican patients with androgen insensitivity
- 1 March 2001
- journal article
- Published by Wiley in Clinical Genetics
- Vol. 59 (3) , 185-188
- https://doi.org/10.1034/j.1399-0004.2001.590307.x
Abstract
The androgen insensitivity syndrome (AIS) is an X-linked form of male pseudohermaphroditism caused by mutations in the androgen receptor (AR) gene. In the present study, we analyzed the AR gene in 8 patients, 4 sporadic and 2 familial cases with the syndrome, using exon-specific polymerase chain reaction, single-stranded conformational polymorphism and sequencing analysis and identified six new single base mutations, including one nonsense mutation at the hinge region of the receptor. These molecular lesions occurred in the steroid-binding domain (SBD) and all but one affected the first nucleotide of their respective codons. A nonsense mutation in exon 4, which converts a glutamine into a premature termination signal (Q657stop), a missense mutation changing arginine instead of glycine (G743R) and a conservative substitution of leucine with valine at amino acid 830 (L830V) were detected in patients with CAIS. Three other missense mutations located in exons 4 (L701I), 5 (A765S), and 6 (Q802R) were present in individuals bearing a partial form of AIS. These data allow us to reaffirm the view that nonsense mutations in the AR results almost invariably in a CAIS phenotype and underly the importance of the SBD for the AR functional activity.Keywords
This publication has 18 references indexed in Scilit:
- Preserved Male Fertility Despite Decreased Androgen Sensitivity Caused by a Mutation in the Ligand-Binding Domain of the Androgen Receptor GeneJournal of Clinical Endocrinology & Metabolism, 2000
- Oligospermic infertility associated with an androgen receptor mutation that disrupts interdomain and coactivator (TIF2) interactionsJournal of Clinical Investigation, 1999
- Point Mutations in the Steroid-Binding Domain of the Androgen Receptor Gene of Five Japanese Patients with Androgen Insensitivity Syndrome.The Tohoku Journal of Experimental Medicine, 1999
- Evolution of the androgen receptor: structure-function implicationsBioEssays, 1998
- Phenotypic diversity in siblings with partial androgen insensitivity syndromeArchives of Disease in Childhood, 1997
- Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor geneEuropean Journal of Pediatrics, 1996
- Complete androgen insensitivity syndrome associated with a de novo mutation of the androgen receptor gene detected by single strand conformation polymorphismThe Journal of Steroid Biochemistry and Molecular Biology, 1993
- Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndromeHuman Molecular Genetics, 1992
- Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity.Proceedings of the National Academy of Sciences, 1989
- Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reactionGenomics, 1989