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

BMC Med Genet 2014 Aug 31;15:95. Epub 2014 Aug 31.

Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, UK.

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.

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Source
http://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881
Publisher Site
http://dx.doi.org/10.1186/s12881-014-0095-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236556PMC
August 2014
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