Wilkie A O, Slaney S F, Oldridge M, Poole M D, Ashworth G J, Hockley A D, Hayward R D, David D J, Pulleyn L J, Rutland P
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Nat Genet. 1995 Feb;9(2):165-72. doi: 10.1038/ng0295-165.
Apert syndrome is a distinctive human malformation comprising craniosynostosis and severe syndactyly of the hands and feet. We have identified specific missense substitutions involving adjacent amino acids (Ser252Trp and Pro253Arg) in the linker between the second and third extracellular immunoglobulin (Ig) domains of fibroblast growth factor receptor 2 (FGFR2) in all 40 unrelated cases of Apert syndrome studied. Crouzon syndrome, characterized by craniosynostosis but normal limbs, was previously shown to result from allelic mutations of the third Ig domain of FGFR2. The contrasting effects of these mutations provide a genetic resource for dissecting the complex effects of signal transduction through FGFRs in cranial and limb morphogenesis.
Apert综合征是一种独特的人类畸形疾病，包括颅缝早闭以及手足严重并指（趾）畸形。在我们研究的40例无亲缘关系的Apert综合征病例中，均发现成纤维细胞生长因子受体2（FGFR2）的第二和第三细胞外免疫球蛋白（Ig）结构域之间的连接区存在涉及相邻氨基酸的特定错义替换（Ser252Trp和Pro253Arg）。以前已表明，以颅缝早闭但四肢正常为特征的Crouzon综合征是由FGFR2第三Ig结构域的等位基因突变所致。这些突变的不同效应为剖析FGFR信号转导在颅骨和肢体形态发生中的复杂作用提供了一种遗传资源。
