Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/ SF-1) and adrenocortical insufficiency.
Steroidogenic factor 1 (NR5A1/ SF-1) plays an essential role in the development of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, controlling expression of their many important genes. The recent description of a 46,XY patient bearing a mutation in the NR5A1 gene, causing male pseudohermaphroditism and adrenal failure, demonstrated the crucial role of SF-1 in male gonadal differentiation. The role of SF-1 in human ovarian development was, until now, unknown. We describe a phenotypically and genotypically normal girl, with signs and symptoms of adrenal insufficiency and no apparent defect in ovarian maturation, bearing a heterozygote G-->T transversion in exon 4 of the NR5A1 gene that leads to the missense R255L in the SF-1 protein. The exchange does not interfere with protein translation and stability. Consistent with the clinical picture, R255L is transcriptionally inactive and has no dominant-negative activity. The inability of the mutant ( MUT) NR5A1/ SF-1 to bind canonical DNA sequences might offer a possible explanation for the failure of the mutant protein to transactivate target genes. This is the first report of a mutation in the NR5A1 gene in a genotypically female patient, and it suggests that NR5A1/ SF-1 is not necessary for female gonadal development, confirming the crucial role of NR5A1/ SF-1 in adrenal gland formation in both sexes.[1]References
- Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency. Biason-Lauber, A., Schoenle, E.J. Am. J. Hum. Genet. (2000) [Pubmed]
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