title: Gene expression changes between patent and fused cranial sutures in a nonsyndromic craniosynostosis population.
abstract: OBJECTIVE
  Craniosynostosis is a premature fusion of 1 or more cranial sutures. It may occur with additional morphological abnormalities (syndromic) or in isolation. Studies suggest that dysregulation of normal cell proliferation, differentiation, and migration has a role in isolated or nonsyndromic craniosynostosis but the molecular mechanisms remain unknown. The aim of this research is to identify genes differentially expressed in prematurely fused human suture compared to patent suture in nonsyndromic craniosynostosis.
  
  
  METHODS
  Bone fragments from synostosed and patent sutures of 7 infants with nonsyndromic craniosynostosis were collected during surgical release of fused sutures. RNA was isolated from the fragments (7 patent and 7 fused) and global gene expression profiled using the Illumina WGE-DASL assay and HumanRef 8.0 Beadchip.
  
  
  RESULTS
  Comparison of mRNA expression in fused and patent suture identified 68 genes significantly differentially expressed and having fold changes ≤ -2.0 and ≥ 2.0 with a false discovery rate adjusted P value at .10 and 136 with adjusted P value of 0.15. SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures. Analysis including only sagittal fused sutures revealed a set of 35 overlapping genes that may be involved in suture patency over all suture types. SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.
  
  
  CONCLUSIONS
  Differentially expressed genes were identified in fused suture relative to patent in a nonsyndromic craniosynostosis population. SFRP2 is likely important in suture patency. Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.
authors.affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland.
authors.forename: Amiee B
authors.initials: AB
authors.lastname: Potter
authors.affiliation: Division of Plastic & Reconstructive Surgery, Department of Surgery, Virginia Commonwealth University Health System, Richmond.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rhodes
authors.affiliation: Department of Neurosurgery, Virginia Commonwealth University Health System, Medical College of Virginia, Richmond.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Vega
authors.affiliation: Department of Neurosurgery, Virginia Commonwealth University Health System, Medical College of Virginia, Richmond.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ridder
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond.
authors.forename: Rita
authors.initials: R
authors.lastname: Shiang
keywords: calvaria; craniosynostosis; gene expression; osteoblastogenesis; sutures