Mutations in SOX9 cause both autosomal sex reversal and campomelic dysplasia

Acta Paediatr Jpn. 1996 Aug;38(4):405-11. doi: 10.1111/j.1442-200x.1996.tb03515.x.


The human testis determining factor (SRY) has been cloned from the Y chromosome. This gene is a dominant inducer of male differentiation. Mutations in the SRY gene result in an XY individual developing as a sex reversed phenotypic female. Sex reversal in humans can also be caused by mutations located in autosomal or X-linked loci. One such sex-reversing locus (SRAI) is associated with the developmental disorder campomelic dysplasia (CD). Both these syndromes were mapped to human chromosome 17q by the identification of balanced reciprocal translocations in five unrelated patients. The translocation breakpoint of one such XY-female CD patient was mapped and the region surrounding it cloned. The closest distal marker used to map the translocation breakpoint was the SOX9 gene. Because of the close proximity of this gene to the breakpoint, it was subjected to mutation analysis in patients without overt chromosome rearrangements. Analysis of DNA from these patients and their parents identified de novo mutations in the SOX9 gene in patients with both autosomal sex reversal and CD. This showed that mutations in the SOX9 gene are responsible for both syndromes.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Disorders of Sex Development*
  • Female
  • Gene Deletion
  • High Mobility Group Proteins / genetics*
  • Humans
  • Male
  • Mutation
  • Nuclear Proteins*
  • Osteochondrodysplasias / genetics*
  • SOX9 Transcription Factor
  • Sex Differentiation
  • Sex-Determining Region Y Protein
  • Transcription Factors / genetics*
  • Translocation, Genetic


  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Nuclear Proteins
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • SRY protein, human
  • Sex-Determining Region Y Protein
  • Transcription Factors