Tartaglia M, Valeri S, Velardi F, Di Rocco C, Battaglia P A
Laboratorio di Biologia Cellulare, Istituto Superiore di Sanità, Rome, Italy.
Hum Genet. 1997 May;99(5):602-6. doi: 10.1007/s004390050413.
Pfeiffer syndrome is a skeletal disorder characterized by craniosynostosis associated with foot and hand anomalies. Mutations in the genes encoding fibroblast growth factor receptors 1 and 2 (FGFR1 and FGFR2) have recently been implicated in the aetiology of such a syndrome, as well as of other craniosynostotic conditions. We now report a novel missense mutation, a G to C transversion at position 1049 (exon IIIa) of FGFR2, detected in a patient with severe Pfeiffer clinical features. The mutation results in the substitution of a cysteine for tryptophan-290 in the third immunoglobulin-like domain and affects both spliceoforms of FGFR2. Mutations causing replacement of tryptophan-290 have also been reported previously in Crouzon syndrome, a similar but clinically distinct craniosynostotic disorder. This finding confirms the involvement of mutations of FGFR2 exon IIIa in Pfeiffer syndrome, and emphasizes both the extensive heterogeneity of the FGFR2 mutations that result in the Pfeiffer phenotype and the perturbations caused by unpaired cysteine residues in receptor dimerization and transduction of the FGFs signal.
法伊弗综合征是一种骨骼疾病，其特征为颅缝早闭并伴有手足异常。最近，编码成纤维细胞生长因子受体1和2（FGFR1和FGFR2）的基因突变被认为与此类综合征以及其他颅缝早闭病症的病因有关。我们现在报告在一名具有严重法伊弗临床特征的患者中检测到一种新的错义突变，即FGFR2第1049位（外显子IIIa）的G到C颠换。该突变导致在第三个免疫球蛋白样结构域中色氨酸-290被半胱氨酸取代，并影响FGFR2的两种剪接形式。先前在克鲁宗综合征（一种类似但临床不同的颅缝早闭疾病）中也报道过导致色氨酸-290被取代的突变。这一发现证实了FGFR2外显子IIIa的突变与法伊弗综合征有关，并强调了导致法伊弗表型的FGFR2突变的广泛异质性以及未配对半胱氨酸残基在受体二聚化和FGF信号转导中所引起的扰动。
