Human Genetics

, Volume 122, Issue 1, pp 63–70

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

Authors

  • Marta Smyk
    • Department of Molecular and Human GeneticsBaylor College of Medicine
    • Department of Medical GeneticsInstitute of Mother and Child
  • Jonathan S. Berg
    • Department of Molecular and Human GeneticsBaylor College of Medicine
  • Amber Pursley
    • Department of Molecular and Human GeneticsBaylor College of Medicine
  • Fiona K. Curtis
    • Disciplines of Medicine and GeneticsMemorial University of Newfoundland
  • Bridget A. Fernandez
    • Disciplines of Medicine and GeneticsMemorial University of Newfoundland
  • Gabriel A. Bien-Willner
    • Department of Molecular and Human GeneticsBaylor College of Medicine
  • James R. Lupski
    • Department of Molecular and Human GeneticsBaylor College of Medicine
    • Department of PediatricsBaylor College of Medicine
    • Texas Children’s Hospital
  • Sau Wai Cheung
    • Department of Molecular and Human GeneticsBaylor College of Medicine
    • Department of Molecular and Human GeneticsBaylor College of Medicine
    • Department of Medical GeneticsInstitute of Mother and Child
Original Investigation

DOI: 10.1007/s00439-007-0373-8

Cite this article as:
Smyk, M., Berg, J.S., Pursley, A. et al. Hum Genet (2007) 122: 63. doi:10.1007/s00439-007-0373-8

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.

Copyright information

© Springer-Verlag 2007