Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Craniosynostosis is the premature fusion of one or more sutures of the skull, which can be syndromic or isolated. Mutations in FGFR1, FGFR2, or FGFR3, among others, are often responsible for these syndromic cases. The associated of FGFR3 mutations with craniosynostosis has been restricted to three mutations, the common p.Pro250Arg in Muenke syndrome, p.Ala391Glu in Crouzon syndrome with acanthosis nigricans, and p.Pro250Leu identified in a family with isolated craniosynostosis. Other FGFR3 mutations result in various skeletal dysplasias: achondroplasia, hypochondroplasia, and thanatophoric dysplasia. Here, we report a novel mutation in exon 8 (IIIc) of FGFR3, p.Ala334Thr, in a young boy with mild craniosynostosis. The mutation segregated with mild craniosynostosis in the family and was absent in 188 normal controls. Alanine 334 is evolutionarily conserved in vertebrates and is located at the amino terminus of the βF loop in the FGFR3c isoform. The mutation is predicted to alter the protein tertiary structure which may impair its binding to its ligand, FGF1. The identification of a mutation in these clinically heterogeneous disorders can aid recurrence risk assessments. Although the implementation of a stepwise screening strategy is useful in diagnostics, mutations in unscreened regions of genes associated with craniosynostosis may explain a small proportion of craniosynostosis cases. © 2011 Wiley Periodicals, Inc.

Original publication




Journal article


American Journal of Medical Genetics, Part A

Publication Date





3050 - 3053