dc.contributor.author | Roscioli, T | en_US |
dc.contributor.author | Kamsteeg, E-J | en_US |
dc.contributor.author | Buysse, K | en_US |
dc.contributor.author | Maystadt, I | en_US |
dc.contributor.author | van Reeuwijk, J | en_US |
dc.contributor.author | van den Elzen, C | en_US |
dc.contributor.author | van Beusekom, E | en_US |
dc.contributor.author | Riemersma, M | en_US |
dc.contributor.author | Pfundt, R | en_US |
dc.contributor.author | Vissers, LELM | en_US |
dc.contributor.author | Schraders, M | en_US |
dc.contributor.author | Altunoglu, U | en_US |
dc.contributor.author | Buckley, MF | en_US |
dc.contributor.author | Brunner, HG | en_US |
dc.contributor.author | Grisart, B | en_US |
dc.contributor.author | Zhou, H | en_US |
dc.contributor.author | Veltman, JA | en_US |
dc.contributor.author | Gilissen, C | en_US |
dc.contributor.author | Mancini, GMS | en_US |
dc.contributor.author | Delrée, P | en_US |
dc.contributor.author | Willemsen, MA | en_US |
dc.contributor.author | Ramadža, DP | en_US |
dc.contributor.author | Chitayat, D | en_US |
dc.contributor.author | Bennett, C | en_US |
dc.contributor.author | Sheridan, E | en_US |
dc.contributor.author | Peeters, EAJ | en_US |
dc.contributor.author | Tan-Sindhunata, GMB | en_US |
dc.contributor.author | de Die-Smulders, CE | en_US |
dc.contributor.author | Devriendt, K | en_US |
dc.contributor.author | Kayserili, H | en_US |
dc.contributor.author | El-Hashash, OAE-F | en_US |
dc.contributor.author | Stemple, DL | en_US |
dc.contributor.author | Lefeber, DJ | en_US |
dc.contributor.author | Lin, Y-Y | en_US |
dc.contributor.author | van Bokhoven, H | en_US |
dc.date.accessioned | 2016-07-22T12:33:58Z | |
dc.date.available | 2012-03-21 | en_US |
dc.date.issued | 2012-05 | en_US |
dc.date.submitted | 2016-05-09T10:49:20.000Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/13623 | |
dc.description.abstract | Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates. | en_US |
dc.description.sponsorship | This project was supported by the Large-Scale Integrating Project GENCODYS-Genetic and Epigenetic Networks in Cognitive DYSfunction (241995), which is funded by the EU FP7 Health program (HvB), the Australian NHMRC with an overseas post-doctoral fellowship (TR), The Prinses Beatrix Fund (grant W.OR09-15 to DL and HvB), the Hersenstichting Nederland (HvB), and an EMBO Long-Term Fellowship (ALTF 805-2009 to KB). All zebrafish work was sponsored by the Wellcome Trust [grant number WT 077047/Z/05/Z] and [grant number WT 077037/Z/05/Z]. NGS experiments were financially supported by the Department of Human Genetics, Nijmegen, The Netherlands, as well as by the Netherlands Organization for Health Research and Development (ZonMW grant 916-86-016 to LELMV). | en_US |
dc.format.extent | 581 - 585 | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Nat Genet | en_US |
dc.rights | “The final publication is available at http://www.nature.com/ng/journal/v44/n5/full/ng.2253.html” | |
dc.subject | Animals | en_US |
dc.subject | Brain | en_US |
dc.subject | Child, Preschool | en_US |
dc.subject | Dystroglycans | en_US |
dc.subject | Embryo, Nonmammalian | en_US |
dc.subject | Eye | en_US |
dc.subject | Glycosylation | en_US |
dc.subject | Humans | en_US |
dc.subject | Mannosyltransferases | en_US |
dc.subject | Muscle Fibers, Skeletal | en_US |
dc.subject | Mutation | en_US |
dc.subject | Walker-Warburg Syndrome | en_US |
dc.subject | Zebrafish | en_US |
dc.title | Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1038/ng.2253 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/22522421 | en_US |
pubs.issue | 5 | en_US |
pubs.notes | Not known | en_US |
pubs.notes | Initial upload not completed by author, 09/05/2016; completed on behalf of the author, 14/07/2016, SM Author manuscript uploaded (not published version as originally identified). | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 44 | en_US |
dcterms.dateAccepted | 2012-03-21 | en_US |