A rare case of 46, XX SRY-negative male with approximately 74-kb duplication in a region upstream of SOX9

Eur J Med Genet. 2013 Dec;56(12):695-8. doi: 10.1016/j.ejmg.2013.10.001. Epub 2013 Oct 18.


The 46, XX male disorder of sex development (DSD) is a rare genetic condition. Here, we report the case of a 46, XX SRY-negative male with complete masculinization. The coding region and exon/intron boundaries of the DAX1, SOX9 and RSPO1 genes were sequenced, and no mutations were detected. Using whole genome array analysis and real-time PCR, we identified a approximately 74-kb duplication in a region approximately 510-584 kb upstream of SOX9 (chr17:69,533,305-69,606,825, hg19). Combined with the results of previous studies, the minimum critical region associated with gonadal development is a 67-kb region located 584-517 kb upstream of SOX9. The amplification of this region might lead to SOX9 overexpression, causing female-to-male sex reversal. Gonadal-specific enhancers in the region upstream of SOX9 may activate the SOX9 expression through long-range regulation, thus triggering testicular differentiation.

Keywords: 46, XX male; Disorder of sex development; SOX9; SRY-negative.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • DAX-1 Orphan Nuclear Receptor / genetics
  • Gene Duplication*
  • Gonadal Dysgenesis, 46,XX / diagnosis
  • Gonadal Dysgenesis, 46,XX / genetics*
  • Humans
  • Male
  • SOX9 Transcription Factor / genetics*
  • Thrombospondins / genetics


  • DAX-1 Orphan Nuclear Receptor
  • NR0B1 protein, human
  • RSPO1 protein, human
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Thrombospondins

Supplementary concepts

  • 46,Xx Gonadal Dysgenesis, Partial Or Complete, Autosomal