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Biochem Biophys Res Commun. 2004 Dec 3;325(1):75-9.

Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation.

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  • 1Glycobiology Research Group, Tokyo Metropolitan Institute of Gerontology, Foundation for Research on Aging and Promotion of Human Welfare, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan.

Abstract

Walker-Warburg syndrome (WWS) is an autosomal recessive developmental disorder characterized by congenital muscular dystrophy, brain malformation, and structural eye abnormalities. WWS is due to defects in protein O-mannosyltransferase 1 (POMT1), which catalyzes the transfer of mannose to protein to form O-mannosyl glycans. POMT1 has been shown to require co-expression of another homologue, POMT2, to have activity. In the present study, mutations in POMT1 genes observed in patients with WWS were duplicated by site-directed mutagenesis. The mutant genes were co-expressed with POMT2 in Sf9 cells and assayed for protein O-mannosyltransferase activity. Expression of all mutant proteins was confirmed by Western blot, but the recombinant proteins did not show any protein O-mannosyltransferase activity. The results indicate that mutations in the POMT1 gene result in a defect of protein O-mannosylation in WWS patients. This may cause failure of binding between alpha-dystroglycan and laminin or other molecules in the extracellular matrix and interrupt normal muscular function and migration of neurons in developing brain.

PMID:
15522202
[PubMed - indexed for MEDLINE]
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