MUTATIONS IN THE FIBROBLAST GROWTH-FACTOR RECEPTOR-2 GENE CAUSE CROUZON-SYNDROME

Crouzon syndrome is an autosomal dominant condition causing premature fusion of the cranial sutures (craniosynostosis) and maps to chromosom e 10q25-q26. We now present evidence that mutations in the fibroblast growth factor receptor 2 gene (FGFR2) cause Crouzon syndrome. We found SSCP variations in the B exon of FGFR2 in nine unrelated affected ind ividuals as well as complete cosegregation between SSCP variation and disease in three unrelated multigenerational families. In four sporadi c cases, the normal parents did not have SSCP variation. Finally, dire ct sequencing has revealed specific mutations in the B exon in all nin e sporadic and familial cases, including replacement of a cysteine in an immunoglobulin-like domain in five patients.