Prevalence of Pro250Arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis

Lancet. 1997 Apr 12;349(9058):1059-62. doi: 10.1016/s0140-6736(96)09082-4.


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.

Findings: 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.

Interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Cohort Studies
  • Craniosynostoses / genetics*
  • Female
  • Heterozygote
  • Humans
  • Infant
  • Male
  • Pedigree
  • Point Mutation*
  • Protein-Tyrosine Kinases*
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor / genetics*


  • Receptors, Fibroblast Growth Factor
  • FGFR3 protein, human
  • Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 3