The human SOX9 gene, located in chromosome region 17q24.1-25.1, encodes a transcription factor involved in chondrogenesis and testis development. The SRY-related SOX9 gene is involved in both chondrogenesis and the early steps of mammalian sex determination.

SOX9 cooperative dimerization is required for chondrogenesis but not for sex determination and may explain why campomelic dysplasia need not be associated with XY sex reversal (#12837698#).

Pathology

 haploinsufficiency of SOX9 by germline mutations or 17q deletions (#10213041#) in

• campomelic dysplasia (MIM.114290)
• +/- male-to-female sex reversal in most, but not all, XY individuals

 duplication of SOX9 in autosomal XX sex reversal (#10588843#)

Differential diagnosis

 tibial bowing

• campomelia
  • Cumming syndrome (Cumming type campomelia)

References

 Koopman P. Sex determination: a tale of two Sox genes. Trends Genet. 2005 Jul;21(7):367-70. PMID: #15949865#

 Harley VR, Clarkson MJ, Argentaro A. The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9. Endocr Rev. 2003 Aug;24(4):466-87. PMID: #12920151#

 Clarkson MJ, Harley VR. Sex with two SOX on: SRY and SOX9 in testis development. Trends Endocrinol Metab. 2002 Apr;13(3):106-11. PMID: #11893523#