Manya Hiroshi, Sakai Keiwa, Kobayashi Kazuhiro, Taniguchi Kiyomi, Kawakita Masao, Toda Tatsushi, Endo Tamao
Glycobiology Research Group, Tokyo Metropolitan Institute of Gerontology, Foundation for Research on Aging and Promotion of Human Welfare, 35-2 Sakaecho, Itabashi-ku, 173-0015, Tokyo, Japan.
Biochem Biophys Res Commun. 2003 Jun 20;306(1):93-7. doi: 10.1016/s0006-291x(03)00924-0.
Muscle-eye-brain disease (MEB), an autosomal recessive disorder, is characterized by congenital muscular dystrophy, brain malformation, and ocular abnormalities. Previously, we found that MEB is caused by mutations in the gene encoding the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1), which is responsible for the formation of the GlcNAcbeta1-2Man linkage of O-mannosyl glycan. Although 13 mutations have been identified in patients with MEB, only the protein with the most frequently observed splicing site mutation has been studied. This protein was found to have no activity. Here, we expressed the remaining mutant POMGnT1s and found that none of them had any activity. These results clearly demonstrate that MEB is inherited as a loss-of-function of POMGnT1.
肌肉-眼-脑疾病（MEB）是一种常染色体隐性疾病，其特征为先天性肌肉萎缩、脑畸形和眼部异常。此前，我们发现MEB是由编码O-连接甘露糖β1,2-N-乙酰葡糖胺基转移酶1（POMGnT1）的基因突变所致，该酶负责O-甘露糖聚糖GlcNAcbeta1-2Man连接的形成。尽管已在MEB患者中鉴定出13种突变，但仅对最常观察到的剪接位点突变的蛋白进行了研究。该蛋白被发现无活性。在此，我们表达了其余的突变型POMGnT1，发现它们均无活性。这些结果清楚地表明，MEB是作为POMGnT1功能丧失而遗传的。
