A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development.
Clin Endocrinol (Oxf)
; 78(4): 545-50, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-22909003
ABSTRACT
BACKGROUND:
NR5A1 loss-of-function mutations are increasingly found to be the cause of 46,XY disorders of sex development (DSD).OBJECTIVE:
To determine the presence of NR5A1 mutations in an Australasian cohort of 17 46,XY DSD patients with presumed androgen insensitivity syndrome (AIS) who were negative for androgen receptor gene (AR) mutation.DESIGN:
Exons 2-7 of NR5A1 were PCR amplified and sequenced. Gene expression and cellular localization studies were performed on a novel NR5A1 variant c.74A>G (p.Y25C) identified in this study.RESULTS:
We identified one novel mutation, c.74A>G (p.Y25C) in a patient characterized by penoscrotal hypospadias with bifid scrotum. He had elevated testosterone and gonadotropins in early infancy. Functional analysis of p.Y25C in vitro demonstrated reduced transcriptional activation by SF-1 and partially impaired nuclear localization in a proportion of transfected human adrenal NCI-H295R cells.CONCLUSION:
This is the first reported case of a DSD patient with a NR5A1 mutation and elevated testosterone levels. Our finding supports evaluation of NR5A1 mutations in 46,XY DSD patients with a range of testosterone levels.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Testosterona
/
Factor Esteroidogénico 1
/
Trastorno del Desarrollo Sexual 46,XY
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
/
Newborn
País/Región como asunto:
Oceania
Idioma:
En
Revista:
Clin Endocrinol (Oxf)
Año:
2013
Tipo del documento:
Article
País de afiliación:
Australia