Mutations of the fibroblast growth factor receptors (FGFRs) cause several dominantly inherited congenital skeletal disorders and syndromes. Recently, these mutations have been suggested to cause either ligand-independent activation of the receptor or a dominant negative inactivation. The analysis of two Japanese patients with Pfeiffer syndrome and postaxial polydactyly of the hand now shows that both carried the same 1119-2A-to-G transition of the FGFR2 gene and this nonsense mutation caused skipping of exon 9(B) and haploinsufficiency of FGFR2.