Novel mutation in the FGFR2 gene at the same codon as the Crouzon syndrome mutations in a severe Pfeiffer syndrome type 2 case

Am J Med Genet. 1998 Jan 23;75(3):252-5. doi: 10.1002/(sici)1096-8628(19980123)75:3<252::aid-ajmg4>;2-s.


We have studied an infant with cloverleaf skull, proptosis, radioulnar synostosis and broad thumbs and great toes diagnosed as Pfeiffer syndrome type 2. However, there were many overlapping findings with Antley-Bixler syndrome. The patient was found to have a G to T mutation in codon 290 exon 7 of the FGFR2 gene leading to a substitution of a cys for the normal trp at this locus. This is the third mutation characterized at this codon; therefore, this locus appears to be a mutational hotspot in the gene. However, the other known mutations lead to a milder, Crouzon-like phenotype. The introduction of an additional cys into a region characterized by immunoglobulin-type loops maintained by cys S-S crosslinking may provide an explanation for the severity of the clinical findings of this child.

Publication types

  • Case Reports

MeSH terms

  • Acrocephalosyndactylia / genetics*
  • Amino Acid Sequence
  • Codon*
  • Craniofacial Dysostosis / genetics*
  • Cysteine / genetics
  • Exons
  • Female
  • Humans
  • Infant, Newborn
  • Molecular Sequence Data
  • Mutation*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / genetics*
  • Tryptophan / genetics


  • Codon
  • Receptors, Fibroblast Growth Factor
  • Tryptophan
  • FGFR2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2
  • Cysteine