Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1

Co-expression of both protein O-mannosyl-transferases 1 and 2 (POMT1 and POMT2; CAZy family GT39) is necessary for enzyme activity, that is mediating the transfer of mannosyl residues to the hydroxyl group of serine or threonine residues of proteins such as alpha-dystroglycan (DAG1; MIM:128239). 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 POMT1 (MIM:607423) results in defective glycosylation of DAG1 and can cause severe congenital muscular dystrophy-dystroglycanopathies ranging from a severe type A, MDDGA1 (brain and eye abnormalities; MIM:236670), through a less severe type B, MDDGB1 (congenital form with mental retardation; MIM:613155) to a milder type C, MDDGC1 (limb girdle form; MIM:609308) (Bertini et al. 2011, Wells 2013).

蛋白质O-甘露糖基转移酶1和2（POMT1和POMT2；属于CAZy家族GT39）的共表达对于酶活性至关重要，即介导甘露糖残基转移至蛋白质如α-肌联蛋白（DAG1；MIM：128239）的丝氨酸或苏氨酸残基的羟基。DAG1是一种细胞表面蛋白，通过将基膜与细胞骨架蛋白相连接，在肌肉、大脑和周围神经的细胞外基质组装中发挥重要作用。POMT1（MIM：607423）的缺陷会导致DAG1糖基化异常，并可引起从严重类型A（MDDGA1，大脑和眼部异常；MIM：236670）至较轻类型C（MDDGC1，肢体围裙型；MIM：609308）的严重先天性肌肉 dystroglycanopathies，其中包括从较轻类型B（MDDGB1，先天性智力障碍；MIM：613155）到各种程度的肌营养不良症（Bertini等，2011，Wells，2013）。