title: Prevalence of Pro250Arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis.
abstract: BACKGROUND
  The C749G (Pro250Arg) mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) has been found in patients with various types of craniosynostosis. We aimed to find out the proportion of cases of apparently non-syndromic coronal craniosynostosis attributable to this mutation.
  
  
  METHODS
  We studied 26 patients with coronal craniosynostosis but no syndromic diagnosis, who were referred to a supra-regional specialist centre. Genomic DNA was analysed by PCR and restriction-enzyme digestion to identify the C749G mutation in FGFR3. Family members of patients found to have the mutation were also tested.
  
  
  RESULTS
  Eight (31%) of the 26 probands were heterozygous for the C749G mutation. In two cases, the mutation showed autosomal dominant transmission with evidence of variable expressivity; the remaining six cases were sporadic. We demonstrated in six families that the mutation had arisen de novo from clinically unaffected parents.
  
  
  CONCLUSIONS
  The C749G mutation in FGFR3 is a frequent cause of apparently non-syndromic coronal craniosynostosis. Our finding will aid genetic counselling and prenatal diagnosis. The mutation rate at this nucleotide is one of the highest described in the human genome.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Moloney
authors.forename: S A
authors.initials: SA
authors.lastname: Wall
authors.forename: G J
authors.initials: GJ
authors.lastname: Ashworth
authors.forename: M
authors.initials: M
authors.lastname: Oldridge
authors.forename: I A
authors.initials: IA
authors.lastname: Glass
authors.forename: C A
authors.initials: CA
authors.lastname: Francomano
authors.forename: M
authors.initials: M
authors.lastname: Muenke
authors.forename: A O
authors.initials: AO
authors.lastname: Wilkie
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D003398:Craniosynostoses / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3