Longitudinal hormonal evaluation in a patient with disorder of sexual development, 46,XY karyotype and one NR5A1 mutation.

Steroidogenic factor 1 (encoded by the NR5A1 gene) is a critical regulator of reproduction, controlling transcription of key genes involved in sexual dimorphism. To date, NR5A1 variants have been found in individuals with a 46,XY karyotype and gonadal dysgenesis, as well as with a wide spectrum of genital anomalies and, in some patients, with adrenal insufficiency. We describe evolution of gonadal function, from the neonatal period to puberty, in a patient with a 46,XY karyotype, a disorder of sexual development, and a mutation (c.691_699dupCTGCAGCTG) in the NR5A1 gene. The patient, ascertained at birth due to ambiguous genitalia, showed normal values of plasma testosterone in the late neonatal period. Evaluation of the hormonal profile over time indicated severe tubular testicular hypofunction suggestive for a 46,XY disorder of gonadal development. A comprehensive review of published reports of 46,XY and disordered sexual development related to the NR5A1 gene confirmed the clinical and hormonal variability in patients with NR5A1 mutations. Analysis of multiple data allowed us to define the most common features associated with NR5A1 mutations. We further confirmed the indication to perform NR5A1 screening in patients with 46,XY karyotype and disordered sexual development even when Müllerian structures appear to be absent and plasma testosterone levels are within the normal range for age.

Pedace L ，Laino L ，Preziosi N ，Valentini MS ，Scommegna S ，Rapone AM ，Guarino N ，Boscherini B ，De Bernardo C ，Marrocco G ，Majore S ，Grammatico P ... -  《-》

Update--steroidogenic factor 1 (SF-1, NR5A1).

Köhler B ，Achermann JC 《Minerva Endocrinologica》

Testosterone production during puberty in two 46,XY patients with disorders of sex development and novel NR5A1 (SF-1) mutations.

Tantawy S ，Lin L ，Akkurt I ，Borck G ，Klingmüller D ，Hauffa BP ，Krude H ，Biebermann H ，Achermann JC ，Köhler B ... -  《-》

46,XY disorder of sex development and developmental delay associated with a novel 9q33.3 microdeletion encompassing NR5A1.

Steroidogenic factor 1 (SF1) is a nuclear receptor encoded by the NR5A1 gene. SF1 affects both sexual and adrenal development through the regulation of target gene expression. Genotypic male and female SF1 knockout mice have adrenal and gonadal agenesis with persistent Müllerian structures and early lethality. There have been several reports of NR5A1 mutations in individuals with 46,XY complete gonadal dysgenesis (CGD) or other disorders of sex development (DSD) with or without an adrenal phenotype. To date microdeletions involving NR5A1 have been reported in only two patients with DSDs. We report a novel microdeletion encompassing NR5A1 in a patient with 46,XY DSD and developmental delay. The phenotypically female patient initially presented with mild developmental delay and dysmorphisms. Chromosome analysis revealed a 46,XY karyotype. A 1.54 Mb microdeletion of chromosome 9q33.3 including NR5A1 was detected by array CGH and confirmed by FISH. Normal maternal FISH results indicated that this was most likely a de novo event. Since most NR5A1 mutations have been ascertained through gonadal or adrenal abnormalities, the additional findings of developmental delay and minor facial dysmorphisms are possibly related to haploinsufficiency of other genes within the 1.54 Mb deleted region. This report further confirms the role of NR5A1 deletions in 46,XY DSD and reinforces the utility of aCGH in the work up of DSDs of unclear etiology.

Brandt T ，Blanchard L ，Desai K ，Nimkarn S ，Cohen N ，Edelmann L ，Mehta L ... -  《-》

Mutation analysis of NR5A1 encoding steroidogenic factor 1 in 77 patients with 46, XY disorders of sex development (DSD) including hypospadias.

Allali S ，Muller JB ，Brauner R ，Lourenço D ，Boudjenah R ，Karageorgou V ，Trivin C ，Lottmann H ，Lortat-Jacob S ，Nihoul-Fékété C ，De Dreuzy O ，McElreavey K ，Bashamboo A ... -  《PLoS One》