Expression profiles of craniosynostosis-derived fibroblasts

Mol Med. 2002 Oct;8(10):638-44.


Background: Craniosynostosis syndromes, a group of connective disorders characterized by abnormalities in vault osteogenesis and premature fusion of bone sutures, are associated with point mutations in FGF receptor family members. The cellular phenotype is characterized by abnormal extracellular matrix turnover.

Material and methods: We used primary cultures of periosteal fibroblasts derived from two different craniosynostosis syndromes, the Apert and Crouzon syndromes. The FGFR2 third immunoglobulin-like domain and its flanking linker regions were analyzed for mutation. DNA microarrays containing 19,200 cDNAs were used to study the gene expression profiles of Apert and Crouzon fibroblasts. The pathologic cells were compared to wild-type human periosteal fibroblasts.

Results: The P253R missense mutation and the G338R mutation were observed in Apert and Crouzon fibroblasts, respectively. The genetic profiles, as evaluated by DNA microarrays, yielded different clusters of expressed sequence tag (ESTs) expression within the experiment. Expression profiles from craniosynostosis-derived fibroblasts differ from those of wild-type fibroblasts (288 human ESTs, p< 0.01, pFDR = 0.12). Furthermore, two ESTs clusters discriminate the Crouzon from Apert fibroblasts. The differentially expressed genes cover a broad range of functional activities, including (1) bone differentiation, (2) cell-cycle regulation, (3) apoptotic stimulation, and (4) signaling transduction, cytoskeleton, and vesicular transport.

Conclusions: The transcriptional program of craniosynostosis fibroblasts differs from that of wild-type fibroblasts. Expression profiles of Crouzon and Apert fibroblasts can also be distinguished by two EST expression clusters, thus hinting at a different genetic background.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrocephalosyndactylia / genetics
  • Adolescent
  • Craniofacial Dysostosis / genetics
  • Craniosynostoses / genetics*
  • DNA Mutational Analysis
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Expressed Sequence Tags
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology*
  • Gene Expression Profiling*
  • Humans
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / genetics
  • Skull / pathology


  • DNA, Complementary
  • Receptors, Fibroblast Growth Factor
  • FGFR2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2