SPECTRUM OF CRANIOSYNOSTOSIS PHENOTYPES ASSOCIATED WITH NOVEL MUTATIONS AT THE FIBROBLAST GROWTH-FACTOR RECEPTOR-2 LOCUS

The causative relationship between several of the syndromic forms of c raniosynostosis and mutations in the fibroblast growth factor receptor (FGFR) loci is now well established. However, within the group of pat ients with craniosynostosis, there are several families and sporadic c ases whose clinical features differ in variable degrees from the class ically described syndromes of craniosynostosis. In this communication we present novel FGFR2 mutations associated with a spectrum of cranios ynostosis phenotypes in 4 sporadic cases and in one family in which cr aniosynostosis segregates. The mutation and phenotype data presented e mphasise the clinical variability of mutations at this locus and under line the plasticity of the phenotype-genotype relationship in this imp ortant group of congenital malformation syndromes. Mutations found wer e tyrosine 105 to cysteine, glycine 338 to glutamic acid, serine 351 t o cysteine and glycine 384 to arginine. These are the first reported m utations in the first immunoglobulin-like loop (tyrosine 105 to cystei ne) and the transmembrane domain (glycine 384 to arginine) of FGFR2, p roviding further insights into the mechanism of abnormal receptor func tion in FGFR2 mutations.