Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal

Am J Hum Genet. 1995 Nov;57(5):1028-36.


Campomelic dysplasia (CD) is a skeletal malformation syndrome frequently accompanied by 46,XY sex reversal. A mutation-screening strategy using SSCP was employed to identify mutations in SOX9, the chromosome 17q24 gene responsible for CD and autosomal sex reversal in man. We have screened seven CD patients with no cytologically detectable chromosomal aberrations and two CD patients with chromosome 17 rearrangements for mutations in the entire open reading frame of SOX9. Five different mutations have been identified in six CD patients: two missense mutations in the SOX9 putative DNA binding domain (high mobility group, or HMG, box); three frameshift mutations and a splice-acceptor mutation. An identical frameshift mutation is found in two unrelated 46,XY patients, one exhibiting a male phenotype and the other displaying a female phenotype (XY sex reversal). All mutations found affect a single allele, which is consistent with a dominant mode of inheritance. No mutations were found in the SOX9 open reading frame of two patients with chromosome 17q rearrangements, suggesting that the translocations affect SOX9 expression. These findings are consistent with the hypothesis that CD results from haploinsufficiency of SOX9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17 / genetics
  • Disorders of Sex Development* / genetics*
  • Female
  • Haplotypes
  • High Mobility Group Proteins / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Osteochondrodysplasias / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • SOX9 Transcription Factor
  • Transcription Factors / genetics*


  • High Mobility Group Proteins
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Transcription Factors

Associated data

  • GENBANK/S74152