PREVALENCE OF PRO250ARG MUTATION OF FIBROBLAST GROWTH-FACTOR RECEPTOR-3 IN CORONAL CRANIOSYNOSTOSIS

Background The C749G (Pro250Arg) mutation in the gene for fibroblast g rowth factor receptor 3 (FGFR3) has been found in patients with variou s types of craniosynostosis. We aimed to find out the proportion of ca ses of apparently nonsyndromic coronal craniosynostosis attributable t o this mutation. Methods We studied 26 patients with coronal craniosyn ostosis but no syndromic diagnosis, who were referred to a supra-regio nal specialist centre. Genomic DNA was analysed by PCR and restriction -enzyme digestion to identify the C749G mutation in FGFR3, Family memb ers of patients found to have the mutation were also tested. Findings Eight (31%) of the 26 probands were heterozygous for the C749G mutatio n. In two cases, the mutation showed autosomal dominant transmission w ith evidence of variable expressivity; the remaining six cases were sp oradic. We demonstrated in six families that the mutation had arisen d e novo from clinically unaffected parents. Interpretation The C749G mu tation in FGFR3 is a frequent cause of apparently non-syndromic corona l craniosynostosis. Our finding will aid genetic counselling and prena tal diagnosis. The mutation rate at this nucleotide is one of the high est described in the human genome.