title: Sequence evaluation of FGF and FGFR gene conserved non-coding elements in non-syndromic cleft lip and palate cases.
abstract: Non-syndromic cleft lip and palate (NS CLP) is a complex birth defect resulting from multiple genetic and environmental factors. We have previously reported the sequencing of the coding region of genes in the fibroblast growth factor (FGF) signaling pathway, in which missense and non-sense mutations contribute to approximately 5%-6% NS CLP cases. In this article we report the sequencing of conserved non-coding elements (CNEs) in and around 11 of the FGF and FGFR genes, which identified 55 novel variants. Seven of variants are highly conserved among >/=8 species and 31 variants alter transcription factor binding sites, 8 of which are important for craniofacial development. Additionally, 15 NS CLP patients had a combination of coding mutations and CNE variants, suggesting that an accumulation of variants in the FGF signaling pathway may contribute to clefting.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Riley
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
mesh_terms: D001665:Binding Sites; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D005091:Exons; D005346:Fibroblast Growth Factors / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D010641:Phenotype; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors