Clustering of FGFR2 gene mutations in patients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses)

A cohort of 36 unrelated German patients with craniosynostosis syndromes of the Crouzon and Pfeiffer type were analyzed for FGFR mutations. Mutations in FGFR2 were identified in 15 Crouzon and 5 Pfeiffer syndrome patients, wh ereas no sequence alterations were found in the remaining patients, even af ter screening of the relevant parts of FGFR1, FGER3, and TWIST. Mutations i n FGFR2 clustered at two critical cysteine residues, 278 and 342, which wer e involved in 18 of 30 cases (60%). These two mutational hot spots, therefo re, are prime targets for an efficient mutation-screening strategy. The spe ctrum of mutations overlapped the two syndromes and thus reflected the phen otypic similarities observed in both patient groups. In 21 families, the or igin of the mutation could be traced by analyzing parents and relatives. El even mutations arose de novo, indicating a high mutation rate for FGFR2. In the 10 familial cases, the clinical presentation varied considerably withi n the pedigree, but both syndromes "bred true," i.e., a Pfeiffer syndrome p henotype was never observed in a Crouzon syndrome family and vice versa. Co pyright (C) 2001 S. Karger AG, Basel.