Human Genetics

, Volume 122, Issue 1, pp 63–70

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

  • Marta Smyk
  • Jonathan S. Berg
  • Amber Pursley
  • Fiona K. Curtis
  • Bridget A. Fernandez
  • Gabriel A. Bien-Willner
  • James R. Lupski
  • Sau Wai Cheung
  • Pawel Stankiewicz
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

Authors and Affiliations

  • Marta Smyk
    • 1
    • 2
  • Jonathan S. Berg
    • 1
  • Amber Pursley
    • 1
  • Fiona K. Curtis
    • 3
  • Bridget A. Fernandez
    • 3
  • Gabriel A. Bien-Willner
    • 1
  • James R. Lupski
    • 1
    • 4
    • 5
  • Sau Wai Cheung
    • 1
  • Pawel Stankiewicz
    • 1
    • 2
  1. 1.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  2. 2.Department of Medical GeneticsInstitute of Mother and ChildWarsawPoland
  3. 3.Disciplines of Medicine and GeneticsMemorial University of NewfoundlandSt. John’sCanada
  4. 4.Department of PediatricsBaylor College of MedicineHoustonUSA
  5. 5.Texas Children’s HospitalHoustonUSA

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