Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation
Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation
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DOI：
10.1016/j.bbrc.2004.10.001
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发表时间：
2004-12-03
影响因子：
3.1
通讯作者：
Endo, T
中科院分区：
文献类型：
--
作者：
Akasaka-Manya, K;Manya, H;Endo, T
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 SO 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. (C) 2004 Elsevier Inc. All rights reserved.
