Unit of Molecular Medicine, Departement of Neurosciences, Bambino Gesù Pediatric Hospital, 4 Piazza S. Onofrio, 00165 Rome, Italy.
Neurogenetics. 2011 Aug;12(3):241-5. doi: 10.1007/s10048-011-0283-8. Epub 2011 Apr 12.
Fibroblast growth factors (FGFs) are important signaling molecules which act during early vertebrate central nervous system development. FGF17, together with FGF8, is a key factor in the patterning of the mid-hindbrain region with a complex picture of spatiotemporal gene expression during the various stages of cerebellar development. Disruption or reduced expression of fgf17 in mice has been associated with cerebellar vermis abnormalities. We have identified a de novo 2.3-Mb deletion of chromosome 8p21.2-p21.3 in a girl with severe growth retardation, seizures, and classical Dandy-Walker malformation. Analysis of gene expression in blood lymphocytes and skin fibroblasts revealed markedly reduced levels of FGF17, which is located 1 Mb from the proximal deletion breakpoint. This is the first report of a human cerebellar malformation associated with transcriptional downregulation of the FGF17 gene.
成纤维细胞生长因子（FGFs）是重要的信号分子，在早期脊椎动物中枢神经系统发育过程中发挥作用。FGF17 与 FGF8 一起，是中后脑区域模式形成的关键因素，在小脑发育的各个阶段具有复杂的时空基因表达图谱。在小鼠中，fgf17 的破坏或表达减少与小脑蚓部异常有关。我们在一名患有严重生长迟缓、癫痫和经典的 Dandy-Walker 畸形的女孩中鉴定出 8p21.2-p21.3 染色体的一个 2.3-Mb 缺失。对血液淋巴细胞和皮肤成纤维细胞中的基因表达分析显示，FGF17 的水平明显降低，FGF17 位于近端缺失断点 1Mb 处。这是首例与 FGF17 基因转录下调相关的人类小脑畸形的报告。
