title: The mutations in FGFR2-associated craniosynostoses are clustered in five structural elements of immunoglobulin-like domain III of the receptor.
abstract: Exons 5 and 7 of the fibroblast growth factor receptor 2 (FGFR2) gene code for immunoglobulin-like domain III (IgIII) and for the region connecting the second and the third Ig domain of the receptor. Numerous mutations in these two exons have been shown to cause various craniosynostotic syndromes. Here, we describe three previously unrecognized mutations at amino acid positions 276, 301, and 314, in one nonspecific craniosynostosis and in two Crouzon patients. We also present a polypeptide model of IgIII of FGFR2. The known mutations involve five distinct structural elements of the receptor. The changes within these elements affect receptor function by various mechanisms, including altered dimerization, truncation, increased mobility between Ig domains, disintegration of IgIII, and alteration of the ligand-binding site.
authors.affiliation: Institut für Humangenetik, Justus-Liebig-Universität, Giessen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Steinberger
authors.forename: G
authors.initials: G
authors.lastname: Vriend
authors.forename: J B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: U
authors.initials: U
authors.lastname: Müller
mesh_terms: D003394:Craniofacial Dysostosis / Q000235:genetics / Q000378:metabolism; D003398:Craniosynostoses / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry* / Q000235:genetics*; D013577:Syndrome
chemical_list: D007136:Immunoglobulins; D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2