Clustering of FGFR2 gene mutations inpatients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses)

Cytogenet Cell Genet. 2000;91(1-4):134-7. doi: 10.1159/000056833.


A cohort of 36 unrelated German patients with craniosynostosis syndromes of the Crouzon and Pfeiffer type were analyzed for FGFR mutations. Mutations in FGFR2 were identified in 25 Crouzon and 5 Pfeiffer syndrome patients, whereas no sequence alterations were found in the remaining patients, even after screening of the relevant parts of FGFR1, FGFR3, and TWIST. Mutations in FGFR2 clustered at two critical cysteine residues, 278 and 342, which were involved in 18 of 30 cases (60%). These two mutational hot spots, therefore, are prime targets for an efficient mutation-screening strategy. The spectrum of mutations overlapped the two syndromes and thus reflected the phenotypic similarities observed in both patient groups. In 21 families, the origin of the mutation could be traced by analyzing parents and relatives. Eleven mutations arose de novo, indicating a high mutation rate for FGFR2. In the 10 familial cases, the clinical presentation varied considerably within the pedigree, but both syndromes "bred true," i.e., a Pfeiffer syndrome phenotype was never observed in a Crouzon syndrome family and vice versa.

MeSH terms

  • Acrocephalosyndactylia / genetics*
  • Acrocephalosyndactylia / physiopathology
  • Amino Acid Sequence
  • Cohort Studies
  • Craniofacial Dysostosis / genetics*
  • Craniofacial Dysostosis / physiopathology
  • Cysteine / genetics
  • DNA Mutational Analysis
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutagenesis / genetics
  • Mutation / genetics*
  • Nuclear Proteins / genetics
  • Pedigree
  • Phenotype
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / chemistry
  • Receptors, Fibroblast Growth Factor / genetics*
  • Syndrome
  • Transcription Factors*
  • Twist-Related Protein 1


  • Nuclear Proteins
  • Receptors, Fibroblast Growth Factor
  • TWIST1 protein, human
  • Transcription Factors
  • Twist-Related Protein 1
  • FGFR2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2
  • Cysteine