NO EVIDENCE OF GENETIC-HETEROGENEITY IN CROUZON CRANIOFACIAL DYSOSTOSIS

Crouzon craniofacial dysostosis (CFD) is an autosomal dominant form of craniosynostosis characterized by an abnormal skull shape, with hyper telorism, prominent eyes and midfacial retrusion. Recently, a gene for CFD has been mapped to chromosome 10q25-26 and mutations in exon B of the fibroblast growth factor receptor 2 (FGFR2) gene have been identi fied. Here, we report the mapping of a CFD gene to chromosome 10q by c lose linkage to probe AFMa197wb1 at locus D10 S1483 in six unrelated f amilies of French ancestry (Z(max) = 4.69 at theta = 0) and provide ad ditional evidence of genetic homogeneity of this condition. In additio n, we report a novel mutation in exon B of the FGFR2 gene (Cys 342 Trp ) in familial CFD and describe recurrent mutations at codon 342 as a p articularly frequent event in CFD. Since mutations in the extracellula r domain of the FGFR2 gene are observed in a few clinically distinct c raniosynostosis syndromes (CFD, Jackson-Weiss, Apert and Pfeiffer), th e present study gives support to the variable clinical expression of F GFR2 mutations in humans.