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

Lucia Pedace, Luigi Laino, Nicoletta Preziosi, Maria Stella Valentini, Salvatore Scommegna, Anna Maria Rapone, Nino Guarino, Brunetto Boscherini, Carmelilia De Bernardo, Giacinto Marrocco, Silvia Majore, Paola Grammatico

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2938-2946
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Issue number11
Publication statusPublished - Nov 1 2014


  • DSD
  • Hormonal screening
  • NR5A1

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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