Pulleyn L J, Reardon W, Wilkes D, Rutland P, Jones B M, Hayward R, Hall C M, Brueton L, Chun N, Lammer E, Malcolm S, Winter R M
Clinical Genetics Unit, Institute of Child Health, London, UK.
Eur J Hum Genet. 1996;4(5):283-91. doi: 10.1159/000472215.
The causative relationship between several of the syndromic forms of craniosynostosis and mutations in the fibroblast growth factor receptor (FGFR) loci is now well established. However, within the group of patients with craniosynostosis, there are several families and sporadic cases whose clinical features differ in variable degrees from the classically described syndromes of craniosynostosis. In this communication we present novel FGFR2 mutations associated with a spectrum of craniosyostosis phenotypes in 4 sporadic cases and in one family in which craniosynostosis segregates. The mutation and phenotype data presented emphasise the clinical variability of mutations at this locus and underline the plasticity of the phenotype-genotype relationship in this important group of congenital malformation syndromes. Mutations found were tyrosine 105 to cysteine, glycine 338 to glutamic acid, serine 351 to cysteine and glycine 384 to arginine. These are the first reported mutations in the first immunoglobulin-like loop (tyrosine 105 to cysteine) and the transmembrane domain (glycine 384 to arginine) of FGFR2, providing further insights into the mechanism of abnormal receptor function in FGFR2 mutations.
几种综合征型颅缝早闭与成纤维细胞生长因子受体（FGFR）基因座突变之间的因果关系现已明确。然而，在颅缝早闭患者群体中，有几个家族和散发病例，其临床特征与经典描述的颅缝早闭综合征存在不同程度的差异。在本报告中，我们展示了与4例散发病例及1个存在颅缝早闭遗传现象的家族中一系列颅缝早闭表型相关的新型FGFR2突变。所呈现的突变和表型数据强调了该基因座突变的临床变异性，并突显了在这一重要的先天性畸形综合征组中表型-基因型关系的可塑性。发现的突变包括酪氨酸105突变为半胱氨酸、甘氨酸338突变为谷氨酸、丝氨酸351突变为半胱氨酸以及甘氨酸384突变为精氨酸。这些是首次报道的FGFR2第一个免疫球蛋白样环（酪氨酸105突变为半胱氨酸）和跨膜结构域（甘氨酸384突变为精氨酸）中的突变，为深入了解FGFR2突变中受体功能异常的机制提供了更多见解。
