Cis-Regulatory Disruption at the SOX9 Locus as a Cause of Pierre Robin Sequence

  • Christopher T. GordonEmail author
  • Sabina Benko
  • Jeanne Amiel
  • Stanislas LyonnetEmail author


Mutations in the coding sequence of SOX9 cause the severe congenital skeletal disorder campomelic dysplasia (CD). A range of genomic lesions in the region upstream of the SOX9 coding sequence are also associated with CD, although often with milder phenotypic effects. Studies in humans and animal models suggest that these non-coding lesions disrupt SOX9 expression in specific tissues during embryonic development. Several lesions at the SOX9 locus, including translocations and microdeletions greater than 1 Mb upstream of the transcription start site, are associated with isolated Pierre Robin sequence (PRS), a craniofacial anomaly that is typically one part of the full-blown CD phenotype. In this chapter, we discuss how the lesions far upstream of SOX9 suggest a requirement for craniofacial-specific regulatory elements during SOX9 transcription in embryonic development and how the cis-ruption of these elements alone might result in isolated PRS, an endophenotype of CD.


Pierre Robin sequence SOX9 Campomelic dysplasia Craniofacial Chondrogenesis Enhancer Conserved non-coding element Cranial neural crest 



Acampomelic campomelic dysplasia


Campomelic dysplasia


Comparative genomic hybridization


Conserved non-coding element


High-mobility group




Pierre Robin sequence


SRY (sex-determining region Y)-box 9


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of GeneticsUniversity Paris Descartes and INSERM U-781ParisFrance

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