Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation
Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation
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DOI：
10.1086/427956
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发表时间：
2005-02-01
影响因子：
9.8
通讯作者：
Econs, MJ
中科院分区：
文献类型：
--
作者：
White, KE;Cabral, JM;Econs, MJ
成纤维细胞生长因子受体 1-3 (FGFR1-3) 基因的激活突变导致多种骨骼疾病。一般来说，FGFR1和FGFR2的突变导致大多数涉及颅缝早闭的综合征，而侏儒综合征主要与FGFR3突变相关。骨发育不良 (OD) 是一种“交叉”疾病，其骨骼表型与 FGFR1、FGFR2 和 FGFR3 突变相关。事实上，OD 患者表现为颅缝早闭、眶上嵴突出、鼻梁凹陷，以及根茎侏儒症和非骨化性骨病变，这些都是该疾病的特征。我们在此证明，OD 是由包含 FGFR1 配体结合和跨膜结构域的高度保守残基的错义突变引起的，从而确定了该受体作为长骨生长负调节因子的新作用。
Activating mutations in the genes for fibroblast growth factor receptors 1-3 (FGFR1-3) are responsible for a diverse group of skeletal disorders. In general, mutations in FGFR1 and FGFR2 cause the majority of syndromes involving craniosynostosis, whereas the dwarfing syndromes are largely associated with FGFR3 mutations. Osteoglophonic dysplasia (OD) is a "crossover" disorder that has skeletal phenotypes associated with FGFR1, FGFR2, and FGFR3 mutations. Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder. We demonstrate here that OD is caused by missense mutations in highly conserved residues comprising the ligand-binding and transmembrane domains of FGFR1, thus defining novel roles for this receptor as a negative regulator of long-bone growth.