1. Prevalence of Pro250Arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis.
- Author
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Moloney DM, Wall SA, Ashworth GJ, Oldridge M, Glass IA, Francomano CA, Muenke M, and Wilkie AO
- Subjects
- Child, Preschool, Cohort Studies, Female, Heterozygote, Humans, Infant, Male, Pedigree, Receptor, Fibroblast Growth Factor, Type 3, Craniosynostoses genetics, Point Mutation, Protein-Tyrosine Kinases, Receptors, Fibroblast Growth Factor genetics
- Abstract
Background: The C749G (Pro250Arg) mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) has been found in patients with various types of craniosynostosis. We aimed to find out the proportion of cases of apparently non-syndromic coronal craniosynostosis attributable to this mutation., Methods: We studied 26 patients with coronal craniosynostosis but no syndromic diagnosis, who were referred to a supra-regional specialist centre. Genomic DNA was analysed by PCR and restriction-enzyme digestion to identify the C749G mutation in FGFR3. Family members of patients found to have the mutation were also tested., Findings: Eight (31%) of the 26 probands were heterozygous for the C749G mutation. In two cases, the mutation showed autosomal dominant transmission with evidence of variable expressivity; the remaining six cases were sporadic. We demonstrated in six families that the mutation had arisen de novo from clinically unaffected parents., Interpretation: The C749G mutation in FGFR3 is a frequent cause of apparently non-syndromic coronal craniosynostosis. Our finding will aid genetic counselling and prenatal diagnosis. The mutation rate at this nucleotide is one of the highest described in the human genome.
- Published
- 1997
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