Complete androgen insensitivity syndrome due to a new frameshift deletion in exon 4 of the androgen receptor gene: functional analysis of the mutant receptor
- Resource Type
- Authors
- Nicolas Poujol; Jean-Marc A. Lobaccaro; Virginie Georget; Charles Sultan; Georges Malpuech; Serge Lumbroso; Albert O. Brinkmann
- Source
- Molecular and Cellular Endocrinology. 111:21-28
- Subject
- Male
medicine.drug_class
Blotting, Western
Molecular Sequence Data
Drug Resistance
Biology
Transfection
urologic and male genital diseases
Biochemistry
Frameshift mutation
Exon
Endocrinology
Complete androgen insensitivity syndrome
medicine
Humans
5-HT5A receptor
Frameshift Mutation
Promoter Regions, Genetic
Molecular Biology
Tyrosine Transaminase
Base Sequence
RNF4
DNA
Exons
medicine.disease
Androgen
Molecular biology
Pedigree
Androgen receptor
Nuclear receptor
Receptors, Androgen
Androgens
Female
France
Gene Deletion
- Language
- ISSN
- 0303-7207
We studied the androgen receptor gene in a large kindred with complete androgen insensitivity syndrome and negative receptor-binding activity, single-strand conformation polymorphism (SSCP) analysis and sequencing identified a 13 base pair deletion within exon 4. This was responsible for a predictive frameshift in the open reading frame and introduction of a premature stop codon at position 783 instead of 919. The deletion was reproduced in androgen receptor wildtype cDNA and transfected into mammalian cells. Western blot showed a smaller androgen receptor of 94 kDa for the transfected mutated cDNA instead of 110 kDa. Androgen-binding assay of the mutated transfected cells assessed the lack of androgen-binding. Gel retardation assay demonstrated the ability of the mutant to bind target DNA; however, the mutant was unable to transactivate a reporter gene. Although the role of the partial deletion in the lack of androgen action was expected, in vitro analyses highlight the role of the abnormal C-terminal portion in the inhibition of the receptor transregulatory activity of the protein causing androgen resistance in this family.