Institute of Physiology, University of Zürich, Zürich, Switzerland.
Hum Mutat. 2009 Dec;30(12):1628-41. doi: 10.1002/humu.21126.
Defects in the biosynthesis of the oligosaccharide precursor for N-glycosylation lead to decreased occupancy of glycosylation sites and thereby to diseases known as congenital disorders of glycosylation (CDG). In the last 20 years, approximately 1,000 CDG patients have been identified presenting with multiple organ dysfunctions. This review sets the state of the art by listing all mutations identified in the 15 genes (PMM2, MPI, DPAGT1, ALG1, ALG2, ALG3, ALG9, ALG12, ALG6, ALG8, DOLK, DPM1, DPM3, MPDU1, and RFT1) that yield a deficiency of dolichol-linked oligosaccharide biosynthesis. The present analysis shows that most mutations lead to substitutions of strongly conserved amino acid residues across eukaryotes. Furthermore, the comparison between the different forms of CDG affecting dolichol-linked oligosaccharide biosynthesis shows that the severity of the disease does not relate to the position of the mutated gene along this biosynthetic pathway.
糖基化的寡糖前体生物合成缺陷会导致糖基化位点占有率降低，从而引发先天性糖基化障碍（CDG）等疾病。在过去的 20 年中，已经发现了约 1000 名患有多种器官功能障碍的 CDG 患者。本文列出了导致多萜醇连接寡糖生物合成缺陷的 15 个基因（PMM2、MPI、DPAGT1、ALG1、ALG2、ALG3、ALG9、ALG12、ALG6、ALG8、DOLK、DPM1、DPM3、MPDU1 和 RFT1）中所有已鉴定的突变，以此列出该领域的最新研究进展。目前的分析表明，大多数突变导致真核生物中强烈保守的氨基酸残基发生取代。此外，对影响多萜醇连接寡糖生物合成的不同形式的 CDG 的比较表明，疾病的严重程度与突变基因在该生物合成途径中的位置无关。
