DPM3 缺陷导致 DPM3-CDG
中文名称
通路描述
DPM3 缺陷导致 DPM3-CDG。DPM 是一种嵌入内质网膜的多亚基蛋白，介导从胞质 GDP-甘露糖向 DOLP 转移甘露糖，形成 DOLPman。DPM1 亚基似乎是该异三聚体的实际催化剂，而 DPM2 和 DPM3 亚基似乎起到稳定作用（Maeda 等，2000）。DPM3 缺陷可导致糖基化发育障碍 1 型（DPM3-CDG，CDG1o；MIM:612937），这是一种多系统疾病，由糖蛋白生物合成缺陷引起，其特征是血清糖蛋白糖基化不足。CDG 1 型疾病导致一系列临床特征，如神经系统发育缺陷、运动发育迟缓、形态异常、低张力、凝血障碍和免疫缺陷（Lefeber 等，2009）。四个生物合成途径依赖 DOLPman；DPM3 缺陷显著降低α- dystroglycan 的 O-甘露糖化，解释了肌营养不良的临床表型，并将糖基化发育障碍与 dystroglycan 疾病联系起来（Lefeber 等，2009）。
英文描述
Defective DPM3 causes DPM3-CDG Dolichyl-phosphate mannosyltransferase (DPM), a heterotrimeric protein embedded in the endoplasmic reticulum membrane, mediates the transfer of mannose (from cytosolic GDP-mannose) to dolichyl phosphate (DOLP) to form dolichyl-phosphate-mannose (DOLPman). The first subunit of the heterotrimer (DPM1) appears to be the actual catalyst, and the other two subunits (DPM2 and 3) appear to stabilise it (Maeda et al. 2000). Defects in DPM3 can cause congenital disorder of glycosylation 1o (DPM3-CDG, CDG1o; MIM:612937), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins. CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency (Lefeber et al. 2009).
Four biosynthetic pathways depend on DOLPman; N-glycosylation, O-mannosylation, C-Mannosylation and GPI-anchor biosynthesis. A defect in DPM3 strongly reduces O-mannosylation of alpha-dystroglycan, explaining the clinical phenotype of muscular dystrophy and linking the congenital disorders of glycosylation with the dystroglycanopathies (Lefeber et al. 2009).
Four biosynthetic pathways depend on DOLPman; N-glycosylation, O-mannosylation, C-Mannosylation and GPI-anchor biosynthesis. A defect in DPM3 strongly reduces O-mannosylation of alpha-dystroglycan, explaining the clinical phenotype of muscular dystrophy and linking the congenital disorders of glycosylation with the dystroglycanopathies (Lefeber et al. 2009).
所含基因
2 个基因