Serum N-glycan and O-glycan analysis by mass spectrometry for diagnosis of congenital disorders of glycosylation
Serum N-glycan and O-glycan analysis by mass spectrometry for diagnosis of congenital disorders of glycosylation
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DOI：
10.1016/j.ab.2013.07.037
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发表时间：
2013-11-15
影响因子：
2.9
通讯作者：
He, Miao
中科院分区：
文献类型：
--
作者：
Xia, Baoyun;Zhang, Wenyue;He, Miao
先天性糖基化紊乱(CDGs)是由参与生物合成糖基化途径的基因缺陷引起的。到目前为止，已知19种不同的N-糖基化基因缺陷，17种O-糖基化基因缺陷，21种多重糖基化基因缺陷。目前CDGS的诊断主要依赖于血清转铁蛋白糖基化的间接分析。仅靠这种分析不足以诊断许多已知的糖基化疾病。为了提高对这些CDG组的诊断，我们开发了结合使用MALDI-TOF/MS和LC-MS/MS技术的血清或血浆N-和O-葡聚糖图谱。使用这种方法，我们分析了9例不同已知的多发性糖基化障碍患者的样本，包括3例COG缺陷，1例TMEM165-CDG，2例PGM1-CDG，3例SLC35A2-CDG，以及1例分子病因不明的I型和II型混合型患者。对各种N-和O-糖链相对数量的测量可以清楚地区分患者和对照组。我们的研究表明，N-和O-葡聚糖组合图谱的结构分析和定量是CDGs的可靠诊断工具。(C)2013 Elsevier Inc.保留所有权利。
Congenital disorders of glycosylation (CDGs) are caused by defects in genes that participate in biosynthetic glycosylation pathways. To date, 19 different genetic defects in N-glycosylation, 17 in O-glycosylation, and 21 in multiple glycosylation are known. Current diagnostic testing of CDGs largely relies on indirect analysis of glycosylation of serum transferrin. Such analysis alone is insufficient to diagnose many of the known glycosylation disorders. To improve the diagnosis of these groups of CDGs, we have developed serum or plasma N- and O-glycan profiling using a combination of MALDI-TOF/MS and LC-MS/MS technologies. Using this approach, we analyzed samples from nine patients with different known multiple glycosylation disorders, including three with COG deficiencies, one with TMEM165-CDG, two with PGM1-CDG, and three with SLC35A2-CDG, and one patient with combined type I and type II of unknown molecular etiology. Measurement of the relative quantities of various N- and O-glycan species clearly differentiates patients and controls. Our study demonstrates that structural analysis and quantitation of combined N- and O-glycan profiles are reliable diagnostic tools for CDGs. (C) 2013 Elsevier Inc. All rights reserved.