Published in

Nature Research, Nature Genetics, 5(44), p. 581-585, 2012

DOI: 10.1038/ng.2253

Links

Tools

Export citation

Search in Google Scholar

Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan

Journal article published in 2012 by Tony Roscioli, Erik-Jan Kamsteeg, Karen Buysse, Isabelle Maystadt, Jeroen van Reeuwijk ORCID, Christa van den Elzen, Ellen van Beusekom, Moniek Riemersma, J. van Reeuwijk, C. van den Elzen, Rolph Pfundt, Lisenka E. L. M. Vissers ORCID, Margit Schraders, Umut Altunoglu, E. van Beusekom and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Orange circle
Postprint: archiving restricted
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

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.