2012-05-01
Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan
Publication
Publication
Nature Genetics , Volume 44 - Issue 5 p. 581- 585
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.
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| doi.org/10.1038/ng.2253, hdl.handle.net/1765/54326 | |
| Nature Genetics | |
| Organisation | Erasmus School of Economics |
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Roscioli, T., Kamsteeg, E.-J., Buysse, K., Maystadt, I., van Reeuwijk, J., van den Elzen, C., … van Bokhoven, H. (2012). Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan. Nature Genetics, 44(5), 581–585. doi:10.1038/ng.2253 |
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