Pubertal development in 46,XY patients with NR5A1 mutations.

Mutations in the NR5A1 gene, encoding the transcription factor Steroidogenic Factor-1, are associated with a highly variable genital phenotype in patients with 46,XY differences of sex development (DSD). Our objective was to analyse the pubertal development in 46,XY patients with NR5A1 mutations by the evaluation of longitudinal clinical and hormonal data at pubertal age. We retrospectively studied a cohort of 10 46,XY patients with a verified NR5A1 mutation and describe clinical features including the external and internal genitalia, testicular volumes, Tanner stages and serum concentrations of LH, FSH, testosterone, AMH, and inhibin B during pubertal transition. Patients who first presented in early infancy due to ambiguous genitalia showed spontaneous virilization at pubertal age accompanied by a significant testosterone production despite the decreased gonadal volume. Patients with apparently female external genitalia at birth presented later in life at pubertal age either with signs of virilization and/or absence of female puberty. Testosterone levels were highly variable in this group. In all patients, gonadotropins were constantly in the upper reference range or elevated. Neither the extent of virilization at birth nor the presence of Müllerian structures reliably correlated with the degree of virilization during puberty. Patients with NR5A1 mutations regardless of phenotype at birth may demonstrate considerable virilization at puberty. Therefore, it is important to consider sex assignment carefully and avoid irreversible procedures during infancy.

Mönig I ，Schneidewind J ，Johannsen TH ，Juul A ，Werner R ，Lünstedt R ，Birnbaum W ，Marshall L ，Wünsch L ，Hiort O ... -  《-》

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 ... -  《-》

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

Köhler B ，Achermann JC 《Minerva Endocrinologica》

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 ... -  《-》

The novel p.Cys65Tyr mutation in NR5A1 gene in three 46,XY siblings with normal testosterone levels and their mother with primary ovarian insufficiency.

Fabbri HC ，de Andrade JG ，Soardi FC ，de Calais FL ，Petroli RJ ，Maciel-Guerra AT ，Guerra-Júnior G ，de Mello MP ... -  《BMC Medical Genetics》