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

Eur J Med Genet. 2009 Mar-Jun;52(2-3):157-60. doi: 10.1016/j.ejmg.2009.02.009. Epub 2009 Mar 6.

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.

Publication types

  • Case Reports

MeSH terms

  • Androgens
  • Chromosome Deletion*
  • Chromosome Disorders / diagnosis
  • Chromosome Disorders / etiology
  • Chromosome Disorders / genetics*
  • Chromosomes, Human, Pair 9*
  • Female
  • Gene Dosage
  • Gonadal Dysgenesis, 46,XY* / diagnosis
  • Gonadal Dysgenesis, 46,XY* / etiology
  • Gonadal Steroid Hormones
  • Humans
  • Infant
  • Steroidogenic Factor 1 / genetics*

Substances

  • Androgens
  • Gonadal Steroid Hormones
  • NR5A1 protein, human
  • Steroidogenic Factor 1