title: C601S mutation in the androgen receptor results in partial loss of androgen function.
abstract: The present study was undertaken on a case of partial androgen insensitivity syndrome to look at the etiology of the disorder. The patient exhibited a female phenotype despite 46,XY chromosome complement. Direct DNA sequencing of coding region of the androgen receptor gene in this case revealed a 2329G>C substitution (cDNA sequence reference) in exon 3 of the gene. The substitution resulted in replacement of Cys with Ser at codon 601 of the ligand-binding domain of the protein. Analyses on 200 control samples revealed absence of this substitution(s). In vitro assays were done using COS-1 cells. The mutation resulted in partial (∼40%) loss of ligand-binding and significant (∼70%) loss of downstream transactivation function. The mutation was absent in the controls. The findings are particularly interesting since another substitution at the same codon (TGC-TTC) has been reported in association with complete androgen insensitivity syndrome.
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Rajender
authors.initials: R
authors.lastname: Singh
authors.forename: Pooja
authors.initials: P
authors.lastname: Singh
authors.forename: Nalini J
authors.initials: NJ
authors.lastname: Gupta
authors.forename: Baidyanath
authors.initials: B
authors.lastname: Chakrabarty
authors.forename: Lalji
authors.initials: L
authors.lastname: Singh
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011944:Receptors, Androgen / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen