A unique 970kb microdeletion in 9q33.3, including the NR5A1 gene in a 46,XY female

Anneke Van Silfhout, Annemieke M. Boot, Trijnie Dijkhuizen, Annemieke Hoek, Rien Nijman, Birgit Sikkema-Raddatz, Conny M. A. van Ravenswaaij-Arts*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)

Abstract

We report on a female patient with XY sex reversal with clitoromegaly, neonatal male testosterone and AMH levels, and a normal urine steroid profile. Array CGH revealed a de novo microdeletion of chromosome 9q33.3, including the NR5A1 gene. NR5A1 encodes for the steroidogenic factor-1 (SF-1) and heterozygous mutations in this gene were recently identified as an important cause of XY sex reversal. However, a deletion of NR5A1 has only been reported once. Patients with a mutation in NR5A1, have severe underandrogenisation with mild testicular dysgenesis. Müllerian structures may be present, while postnatal testosterone levels may be normal. This points towards a predominantly early embryonic effect of low, local, androgen levels, with or without reduced AMH levels. We recommend not only NR5A1 mutation screening, but also copy number analysis in patients with 46,XY sex reversal of unknown cause, even in the absence of dysmorphisms or congenital abnormalities.

Original languageEnglish
Pages (from-to)157-160
Number of pages4
JournalEuropean journal of medical genetics
Volume52
Issue number2-3
DOIs
Publication statusPublished - 10-Mar-2009

Keywords

  • XY sex reversal
  • Prominent clitoris
  • Disorders of sex development (DSD)
  • Steroidogenic Factor-1 (SF-1)
  • NR5A1
  • Deletion 9q33.3
  • Array CGH
  • STEROIDOGENIC FACTOR-I
  • XY SEX REVERSAL
  • ADRENAL INSUFFICIENCY
  • BINDING DOMAIN
  • NR5A1
  • DISORDERS
  • MUTATIONS
  • DELETION

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