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.