Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3

Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1; CAZy family GT61; MIM:606822) mediates the transfer of N-acetylglucosaminyl (GlcNAc) residues to mannosylated proteins such as mannose-O-serine-dystroglycan (man-O-Ser-DAG1). DAG1 is a cell surface protein that plays an important role in the assembly of the extracellular matrix in muscle, brain, and peripheral nerves by linking the basal lamina to cytoskeletal proteins. Defects in POMGNT1 (MIM:606822) result in disrupted glycosylation of DAG1 and can cause severe congenital muscular dystrophy-dystroglycanopathies ranging from a severe type A3 (MDDGA3; MIM:253280), through a less severe type B3 (MDDGB3; MIM:613151) to a milder type C3 (MDDGC3; MIM:613157) (Bertini et al. 2011, Wells 2013).

蛋白质O-连接甘露糖β-1,2-乙酰葡萄糖胺基转移酶1（POMGNT1；CAZy家族GT61；MIM:606822）介导N-乙酰葡萄糖胺基（GlcNAc）残基向甘露糖化蛋白如甘露糖-O-丝氨酸-肌萎缩蛋白（man-O-Ser-DAG1）的转移。DAG1是一种细胞表面蛋白，通过将基膜与细胞骨架蛋白连接起来，在肌肉、大脑和周围神经细胞外基质的组装中发挥着重要作用。POMGNT1（MIM:606822）的缺陷会导致DAG1糖基化破坏，并可能引发从严重类型A3（MDDGA3；MIM:253280）至较轻类型B3（MDDGB3；MIM:613151），乃至更轻微的类型C3（MDDGC3；MIM:613157）的严重先天性肌营养不良-肌萎缩蛋白病（Bertini等，2011年，Wells，2013年）。