Human androgen insensitivity due to point mutations encoding amino acid substitutions in the androgen receptor steroid-binding domain

Human Mutation
K MuronoT R Brown

Abstract

Mutations of the human androgen receptor gene were identified in five subjects from four families with androgen insensitivity syndrome. Individual exons of the androgen receptor gene were amplified by the polymerase chain reaction from genomic DNA and screened for sequence-dependent differences in their melting characteristics by denaturing gradient gel electrophoresis. DNA fragments from exons with altered mobility were sequenced. Four different single nucleotide base substitutions were found within exons 5, 6, and 7 encoding the steroid-binding domain of the androgen receptor. In one subject with ambiguous genitalia, amino acid residue 763 was changed from tyrosine to cysteine (TAC-->TGC; Y763C). Four subjects, including two siblings, had complete androgen insensitivity. In one subject, residue 779 was changed from arginine to tryptophan (CGC-->TGG; R779W), another subject (M807V) had a substitution of valine (GTG) for methionine (ATG) residue at position 807, and the two siblings (R855C) had a mutation in residue 855 changing arginine (CGC) to cysteine (TGC). Binding of the synthetic androgen ligand, methyltrienolone (R1881), by the mutant receptor Y763C was decreased by 54% compared to the normal receptor. Transcriptional a...Continue Reading

References

Nov 1, 1992·The Journal of Clinical Investigation·M J McPhaulJ D Wilson
Mar 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·A O BrinkmannG Romalo
Sep 1, 1982·Molecular and Cellular Biology·C M GormanB H Howard
Jan 1, 1993·European Journal of Pediatrics·T R BrownZ Zhou
Dec 1, 1982·Molecular and Cellular Biology·G AnL Siminovitch

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Citations

Jul 1, 1995·Trends in Endocrinology and Metabolism : TEM·T R Brown
Feb 7, 2017·Nature Communications·Marta NadalEva Estébanez-Perpiñá
Dec 9, 2009·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·K AllanG Devereux
Mar 18, 2006·Arquivos brasileiros de endocrinologia e metabologia·Karla F S MeloIvo J P Arnhold

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