Fibroblast Growth Factor Receptor‐2 Mutations in Craniosynostosis a
Fibroblast Growth Factor Receptor‐2 Mutations in Craniosynostosis a
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DOI：
10.1111/j.1749-6632.1996.tb56255.x
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发表时间：
1996-06
影响因子：
5.2
通讯作者：
S. Malcolm;W. Reardon
中科院分区：
文献类型：
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作者：
S. Malcolm;W. Reardon
人类成纤维细胞生长因子受体 2 (FGFR2) 基因突变会导致多种不同的基因综合征；克鲁宗、菲佛、阿佩尔和杰克逊-韦斯。所有这些显性遗传综合征均涉及颅缝早闭或颅骨缝过早融合。然而，手指受累的情况各不相同，从克鲁宗综合征的正常手指和脚趾到阿佩尔综合征的严重手脚并指。成纤维细胞生长因子受体是具有三个细胞外免疫球蛋白 (Ig) 样结构域的跨膜信号分子。两个令人费解的特征是，在Crouzon和Pfeiffer综合征中发现了相同的核苷酸变化，其次，Pfeiffer综合征的非常相似的表型可以由FGFR1和FGFR2中的突变引起。在 IgII-IgIII 连接子（Pfeiffer、Apert）中发现了突变，但主要发生在第三个 IgIII 结构域中。在克鲁宗综合征中，已报道了许多突变，但它们通常是复发性的，并且有四种主要类型：从 IgIII 环中去除一个半胱氨酸、半胱氨酸附近高度保守残基的错义突变、新半胱氨酸的产生和剪接突变。遗传学方法在阐明这些分子的作用方面非常具有启发性。
Mutations in the human fibroblast growth factor receptor 2 (FGFR2) gene result in several different genetically defined syndromes; Crouzon, Pfeiffer, Apert, and Jackson-Weiss. All these syndromes, which are dominantly inherited, involve craniosynostosis, or premature fusion of the cranial sutures. However, there is variable involvement of digits, from normal fingers and toes in Crouzon syndrome to severe syndactyly of the hands and feet in Apert syndrome. Fibroblast growth factor receptors are transmembrane signaling molecules with three extracellular immunoglobulin (Ig)-like domains. Two puzzling features are that identical nucleotide changes have been found in Crouzon and Pfeiffer syndromes and, secondly, that a very similar phenotype of Pfeiffer syndrome can be caused by mutations in either FGFRl and FGFR2. Mutations are found in the IgII-IgIII linker (Pfeiffer, Apert), but predominantly in the third IgIII domain. In Crouzon syndrome many mutations have been reported, but they are often recurrent and of four major types: removal of one of the cysteines from the IgIII loop, missense mutations of highly conserved residues near the cysteine, creation of new cysteines, and splice mutations. A genetic approach has been very revealing in elucidating the role of these molecules.