Abstract
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.
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Acknowledgments
We are grateful to the patient and her family. This work was supported by grants from Telethon (project GGP08145), the Fondazione Pierfranco e Luisa Mariani ONLUS, and the Italian Ministry of Health. We are grateful to Dr. Rosalba Carrozzo (Unit of Molecular Medicine) and Dr. Andrea Masotti (Gene Expression–Microarrays Laboratory) of the Bambino Gesù Pediatric Hospital for their precious help.
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Zanni, G., Barresi, S., Travaglini, L. et al. FGF17, a gene involved in cerebellar development, is downregulated in a patient with Dandy–Walker malformation carrying a de novo 8p deletion. Neurogenetics 12, 241–245 (2011). https://doi.org/10.1007/s10048-011-0283-8
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DOI: https://doi.org/10.1007/s10048-011-0283-8