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

Authors
  • Smyk, Marta
  • Berg, Jonathan S
  • Pursley, Amber
  • Curtis, Fiona K
  • Fernandez, Bridget A
  • Bien-Willner, Gabriel A
  • Lupski, James R
  • Cheung, Sau Wai
  • Stankiewicz, Pawel
Type
Published Article
Journal
Human Genetics
Publisher
Springer-Verlag
Publication Date
Aug 01, 2007
Volume
122
Issue
1
Pages
63–70
Identifiers
PMID: 17503084
Source
Medline
License
Unknown

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.

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