Male-to-female sex reversal associated with an approximately 250 kb deletion upstream of NR0B1 (DAX1)

Hum Genet. 2007 Aug;122(1):63-70. doi: 10.1007/s00439-007-0373-8. Epub 2007 May 15.

Abstract

Deletion of the dosage sensitive gene NR0B1 encoding DAX1 on chromosome Xp21.2 results in congenital adrenal hypoplasia (AHC), whereas NR0B1 duplication in 46,XY individuals leads to gonadal dysgenesis and a female phenotype. We describe a 21-year-old 46,XY female manifesting primary amenorrhea, a small immature uterus, gonadal dysgenesis, and notably absent adrenal insufficiency with a submicroscopic (257 kb) deletion upstream of NR0B1. We hypothesize that loss of regulatory sequences may have resulted in position effect up-regulation of DAX1 expression, consistent with phenotypic consequences of NR0B1 duplication. We propose that this genomic region and by extension those surrounding the dosage sensitive SRY, SOX9, SF1, and WNT-4 genes, should be examined for copy-number variation in patients with sex reversal.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • DAX-1 Orphan Nuclear Receptor
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Disorders of Sex Development*
  • Female
  • Gene Deletion*
  • Humans
  • Male
  • Receptors, Retinoic Acid / genetics*
  • Repressor Proteins / genetics*

Substances

  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • NR0B1 protein, human
  • Receptors, Retinoic Acid
  • Repressor Proteins