Apparently synonymous substitutions in FGFR2 affect splicing and result in mild Crouzon syndrome.

Abstract

BACKGROUND:

Mutations of fibroblast growth factor receptor 2 (FGFR2) account for a higher proportion of genetic cases of craniosynostosis than any other gene, and are associated with a wide spectrum of severity of clinical problems. Many of these mutations are highly recurrent and their associated features well documented. Crouzon syndrome is typically caused by heterozygous missense mutations in the third immunoglobulin domain of FGFR2.

CASE PRESENTATION:

Here we describe two families, each segregating a different, previously unreported FGFR2 mutation of the same nucleotide, c.1083A>G and c.1083A>T, both of which encode an apparently synonymous change at the Pro361 codon. We provide experimental evidence that these mutations affect normal FGFR2 splicing and document the clinical consequences, which include a mild Crouzon syndrome phenotype and reduced penetrance of craniosynostosis.

CONCLUSIONS:

These observations add to a growing list of FGFR2 mutations that affect splicing and provide important clinical information for genetic counselling of families affected by these specific mutations.

• Authors: Aimee L Fenwick, Jacqueline A C Goos, Julia Rankin, Helen Lord, Tracy Lester, A Jeannette M Hoogeboom, Ans M W van den Ouweland, Steven A Wall, Irene M J Mathijssen, Andrew O M Wilkie
• Journal: BMC medical genetics (BMC Med Genet) Vol. 15 Pg. 95 (Aug 31 2014) ISSN: 1471-2350 [Electronic] England
• PMID: 25174698 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FGFR2 protein, human
• Receptor, Fibroblast Growth Factor, Type 2

Topics

• Amino Acid Substitution
• Craniofacial Dysostosis (genetics, pathology)
• Craniosynostoses (genetics, pathology)
• Exons
• Female
• Heterozygote
• Humans
• Male
• Mutation, Missense
• Pedigree
• RNA Splicing
• Receptor, Fibroblast Growth Factor, Type 2 (genetics)