title: FGF17, a gene involved in cerebellar development, is downregulated in a patient with Dandy-Walker malformation carrying a de novo 8p deletion.
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.
authors.affiliation: Unit of Molecular Medicine, Departement of Neurosciences, Bambino Gesù Pediatric Hospital, 4 Piazza S. Onofrio, 00165 Rome, Italy. ginevra.zanni@opbg.net
authors.forename: Ginevra
authors.initials: G
authors.lastname: Zanni
authors.forename: Sabina
authors.initials: S
authors.lastname: Barresi
authors.forename: Lorena
authors.initials: L
authors.lastname: Travaglini
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Teresa
authors.initials: T
authors.lastname: Rizza
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.forename: Stefano
authors.initials: S
authors.lastname: Cianfarani
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Valeriani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: Letizia
authors.initials: L
authors.lastname: Da Sacco
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Enrico Silvio
authors.initials: ES
authors.lastname: Bertini
mesh_terms: D002531:Cerebellum / Q000196:embryology / Q000254:growth & development; D002675:Child, Preschool; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D003616:Dandy-Walker Syndrome / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans
chemical_list: C496456:FGF8 protein, human; D051524:Fibroblast Growth Factor 8