Title: Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan
Authors: Roscioli, Tony ×
Kamsteeg, Erik-Jan
Buysse, Karen
Maystadt, Isabelle
van Reeuwijk, Jeroen
van den Elzen, Christa
van Beusekom, Ellen
Riemersma, Moniek
Pfundt, Rolph
Vissers, Lisenka E L M
Schraders, Margit
Altunoglu, Umut
Buckley, Michael F
Brunner, Han G
Grisart, Bernard
Zhou, Huiqing
Veltman, Joris A
Gilissen, Christian
Mancini, Grazia M S
Delrée, Paul
Willemsen, Michèl A
Ramadža, Danijela Petković
Chitayat, David
Bennett, Christopher
Sheridan, Eamonn
Peeters, Els A J
Tan-Sindhunata, Gita M B
de Die-Smulders, Christine E
Devriendt, Koenraad
Kayserili, Hülya
El-Hashash, Osama Abd El-Fattah
Stemple, Derek L
Lefeber, Dirk J
Lin, Yung-Yao
van Bokhoven, Hans #
Issue Date: May-2012
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:44 issue:5 pages:581-585
Article number: 10.1038/ng.2253
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 α-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 α-dystroglycan. These results implicate ISPD in α-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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