title: Apparently synonymous substitutions in FGFR2 affect splicing and result in mild Crouzon syndrome.
abstract: BACKGROUND
  Mutations of fibroblast growth factor receptor 2 (FGFR2) account for a higher proportion of genetic cases of craniosynostosis than any other gene, and are associated with a wide spectrum of severity of clinical problems. Many of these mutations are highly recurrent and their associated features well documented. Crouzon syndrome is typically caused by heterozygous missense mutations in the third immunoglobulin domain of FGFR2.
  
  
  METHODS
  Here we describe two families, each segregating a different, previously unreported FGFR2 mutation of the same nucleotide, c.1083A>G and c.1083A>T, both of which encode an apparently synonymous change at the Pro361 codon. We provide experimental evidence that these mutations affect normal FGFR2 splicing and document the clinical consequences, which include a mild Crouzon syndrome phenotype and reduced penetrance of craniosynostosis.
  
  
  CONCLUSIONS
  These observations add to a growing list of FGFR2 mutations that affect splicing and provide important clinical information for genetic counselling of families affected by these specific mutations.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Fenwick
authors.forename: Jacqueline A C
authors.initials: JA
authors.lastname: Goos
authors.forename: Julia
authors.initials: J
authors.lastname: Rankin
authors.forename: Helen
authors.initials: H
authors.lastname: Lord
authors.forename: Tracy
authors.initials: T
authors.lastname: Lester
authors.forename: A Jeannette M
authors.initials: AJ
authors.lastname: Hoogeboom
authors.forename: Ans M W
authors.initials: AM
authors.lastname: van den Ouweland
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wall
authors.forename: Irene M J
authors.initials: IM
authors.lastname: Mathijssen
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, UK. andrew.wilkie@imm.ox.ac.uk.
authors.forename: Andrew O M
authors.initials: AO
authors.lastname: Wilkie
mesh_terms: D019943:Amino Acid Substitution; D003394:Craniofacial Dysostosis / Q000235:genetics* / Q000473:pathology*; D003398:Craniosynostoses / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D012326:RNA Splicing; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*
chemical_list: C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2