非综合征性唇腭裂病例中FGF和FGFR基因保守非编码元件的序列评估
Sequence evaluation of FGF and FGFR gene conserved non-coding elements in non-syndromic cleft lip and palate cases.
作者信息
Riley Bridget M, Murray Jeffrey C
机构信息
Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
出版信息
Am J Med Genet A. 2007 Dec 15;143A(24):3228-34. doi: 10.1002/ajmg.a.31965.
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.
摘要
非综合征性唇腭裂（NS CLP）是一种由多种遗传和环境因素导致的复杂出生缺陷。我们之前报道过对成纤维细胞生长因子（FGF）信号通路中基因编码区的测序，其中错义突变和无义突变约占5%-6%的NS CLP病例。在本文中，我们报道了对11个FGF和FGFR基因及其周围保守非编码元件（CNE）的测序，共鉴定出55个新变体。其中7个变体在≥8个物种中高度保守，31个变体改变了转录因子结合位点，其中8个对颅面发育很重要。此外，15名NS CLP患者同时存在编码突变和CNE变体，这表明FGF信号通路中变体的积累可能导致腭裂。
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