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

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• 作者：Akasaka-Manya ; Keiko ; Manya ; Hiroshi ; Endo ; Tamao
• 关键词：Walker??????Warburg syndrome ; Muscular dystrophy ; Glycosyltransferase ; Mutation ; POMT1
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：December 3, 2004
• 年：2004
• 卷：325
• 期：1
• 页码：75-79
• 全文大小：375 K

文摘

WalkeraaaWarburg 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 aa-dystroglycan and laminin or other molecules in the extracellular matrix and interrupt normal muscular function and migration of neurons in developing brain.