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)
- penile hypospadias
- scrotal hypospadias
SOX9-associated disorder of sexual differentiation
Diagnostic pathology
SOX-9 is apparently common to both notochordal and cartilaginous differentiation, and is not useful in the chordoma-chondrosarcoma differential diagnosis. (18820665)
Reviews
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
References
FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD). Hersmus R, Kalfa N, de Leeuw B, Stoop H, Oosterhuis JW, de Krijger R, Wolffenbuttel KP, Drop SL, Veitia RA, Fellous M, Jaubert F, Looijenga LH. J Pathol. 2008 May;215(1):31-8. PMID: 18348162
Oakley GJ, Fuhrer K, Seethala RR. Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Mod Pathol. 2008 Sep 26. PMID: 18820665