In vitro functional characterization of androgen receptor gene mutations at arginine p.856 of the ligand-binding-domain associated with androgen insensitivity syndrome.
J Steroid Biochem Mol Biol
; 208: 105834, 2021 04.
Article
en En
| MEDLINE
| ID: mdl-33548461
ABSTRACT
Androgens are critical for male sex differentiation. Their actions are mediated by the androgen receptor (AR). Mutations disrupting AR function result in the androgen insensitivity syndrome (AIS). In this study, we identified in a patient with complete AIS, a novel AR mutation p.R856L. To investigate the functional properties of p.R856L, we performed functional studies. In comparison, we have characterized two already described mutations p.R856H and p.R856C. We used a model composed of two different promoters fused to a reporter gene, two cell lines, and showed that all mutations were able to transactivate the (ARE)2-TATA promoter expressed in CHO cells more highly. Moreover, we confirmed the pathogenicity of the p.R856L and p.R856C mutations, and their associations with complete AIS. In contrast, the p.R856H mutation, which is associated with a spectrum of AIS phenotypes, showed less severe transcriptional constraints. Altogether, our studies allowed us to better characterize arginine residue at p.R856 position.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diferenciación Sexual
/
Síndrome de Resistencia Androgénica
/
Receptores Androgénicos
/
Andrógenos
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania