MUTATIONS IN THE 3RD IMMUNOGLOBULIN DOMAIN OF THE FIBROBLAST GROWTH-FACTOR RECEPTOR-2 GENE IN CROUZON SYNDROME

Craniosynostosis, which affects approximately 1 in 2000 children, is t he result of the abnormal development and/or premature fusion of the c ranial sutures, Studies of mutations in patients with craniosynostosis have shown that the family of fibroblast growth factor receptor genes are extremely important in the correct formation of the skull, and di gits, Mutations in the third immunoglobulin domain of fibroblast growt h factor receptor 2 (FGFR2), in part of the molecule corresponding to a tissue specific isoform (IIIc), can cause both Crouzon and Pfeiffer syndromes, Two specific mutations in the linking region between the se cond and third immunoglobulin domains of FGFR2 occur in Apert syndrome , We present here mutations associated with the Crouzon syndrome, also in the third immunoglobulin domain but in an upstream exon, This exon is expressed in both tissue isoforms, Five different mutations were d etected in 11 unrelated individuals, A cysteine to phenylalanine chang e was found in six individuals, This cysteine forms half of the disulp hide bridge maintaining the secondary structure of the immunoglobulin domain, The first deletion within an FGFR gene is reported, Together w ith mutations in exon IIIc these account for 25 mutations out of 40 Cr ouzon patients studied in our combined series (5).