A novel mutation in the accessory DNA-binding domain of human steroidogenic factor 1 causes XY gonadal dysgenesis without adrenal insufficiency.
Eur J Endocrinol
; 157(2): 233-8, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17656604
ABSTRACT
OBJECTIVE:
Steroidogenic factor 1 (SF1), officially designated NR5A1, is a nuclear receptor that plays key roles in endocrine development and function. Previous reports of human SF1 mutations revealed a spectrum of phenotypes affecting adrenal function and/or gonadal development and sex differentiation. We present the clinical phenotype and functional effects of a novel SF1 mutation. PATIENT The patient is a 22-year-old 46, XY Japanese patient who presented with dysgenetic testes, atrophic vasa deferentia and epididymides, lack of Müllerian structures, and clitoromegaly. Endocrine studies revealed normal adrenal function.RESULTS:
Analysis of the SF1 gene revealed compound heterozygosity for a previously described p.G146A polymorphism and a novel missense mutation (p.R84C) in the accessory DNA-binding domain. The father carried the p.G146A polymorphism and the mother had the p.R84C mutation; both were clinically and reproductively normal. Functional studies demonstrated that the p.R84C SF1 had normal nuclear localization but decreased DNA-binding affinity and transcriptional activity compared with wild-type SF1; it did not exhibit any dominant negative activity.CONCLUSIONS:
These results describe the human phenotype that results from compound heterozygosity of the p.G146A polymorphism and a novel p.R84C mutation of SF1, thereby extending the spectrum of human SF1 mutations that impair testis development and sex differentiation in a sex-limited manner while preserving normal adrenal function.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Receptores Citoplasmáticos e Nucleares
/
Proteínas de Homeodomínio
/
Proteínas de Ligação a DNA
/
Disgenesia Gonadal 46 XY
Tipo de estudo:
Etiology_studies
Limite:
Adult
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article