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Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of ?-dystroglycan.
- Source :
- Nature Genetics; May2012, Vol. 44 Issue 5, p581-585, 5p
- Publication Year :
- 2012
-
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 ?-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 ?-dystroglycan. These results implicate ISPD in ?-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10614036
- Volume :
- 44
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Nature Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 74604499
- Full Text :
- https://doi.org/10.1038/ng.2253