A novel mutation in the accessory DNA-binding domain of human steroidogenic factor I causes XY gonadal dysgenesis without adrenal insufficiency

作者：Reuter Anne L; Goji Katsumi^*; Bingham Nathan C; Matsu Masafumi; Parker Keith L

来源：European Journal of Endocrinology, 2007, 157(2): 233-238.

DOI：10.1530/EJE-07-0113

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 Mullerian 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 rnutation: 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.

• 出版日期2007-8