Two of them showed a 1036T --> C mutation in the fibroblast growth factor receptor 2 (FGFR2) gene, that was earlier reported in PS and in Crouzon syndrome.
Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have previously been identified in Crouzon syndrome, an autosomal dominant condition involving premature fusion of the cranial sutures.
Gain-of-function missense mutations in FGF receptor 2 (FGFR2) are responsible for a variety of craniosynostosis syndromes including Apert syndrome (AS), Pfeiffer syndrome (PS) and Crouzon syndrome (CS).
Recently mutations in fibroblast growth factor receptor 2 (FGFR2) have been found in patients with another craniosynostotic syndrome, Crouzon syndrome.
We have identified a novel missense mutation in the FGFR2 gene that predicts an Ala362Ser substitution shared by all family members affected by Crouzon syndrome and by a "clinically normal"-appearing father.
Using the published primers for PCR, a patient with Crouzon syndrome was found to be homozygous for a mutation that results in a Q289P amino acid substitution in FGFR2.
The Crouzon syndrome, which is associated with fibroblast growth factor receptor (FGFR2) mutations, is characterized by premature fusion of cranial sutures.
Genotype-phenotype analyses based on our cohort and previous studies further indicate that in spite of some overlap, PS and CS are preferentially accounted for by two distinct sets of FGFR2 mutations.
Despite long axial lengths, shallow anterior chambers with occluded angles are possible in Crouzon syndrome and are most likely caused by FGFR2-related anterior segment dysgenesis.
We measured the foramen magnum area (FMA) and its sagittal and transversal components: the right, left, and mean area of the jugular foramen; the posterior fossa volume; and the cerebellar volume on preoperative millimetric computed tomography scan slices in 31 children with an FGFR2 mutation (14 with Crouzon syndrome, 11 with Apert syndrome, and 6 with Pfeiffer syndrome).
Thus the human developmental abnormality Crouzon syndrome arises from constitutive activation of FGFR2 due to aberrant intermolecular disulfide-bonding.
Given that a mutation in codon 342 was found in 8 out of 17 cases and that in 9 cases the mutation occurred at five additional positions, codon 342 of exon B of the FGFR2 gene may be predisposed to mutations in Crouzon syndrome.