Abstract
Congenital disorders of glycosylation (CDG), an increasingly recognized group of diseases affecting glycosylation, comprise the largest known subgroup involving approximately 100 responsible genes related to N-glycosylation. This subgroup presents as various molecular abnormalities, of either the CDG-I or the CDG-II type, attributable to lack of glycans or abnormal glycoform profiles, respectively. The most effective approach to identifying N-glycosylation disorders is mass spectrometry (MS) using either released glycans, intact glycoproteins or proteolytic peptides as the analyte. Among these, MS of tryptic peptides of transferrin reliably identifies the signature peptides characteristic of CDG-I and II. In the present study, matrix-assisted laser desorption/ionization (MALDI) MS was applied to various N-glycosylation disorders including ALG1-CDG, B4GALT1-CDG, SLC35A2-CDG, ATP6V0A2-CDG, TRAPPC11-CDG and MAN1B1-CDG. This method does not require prior enrichment of glycopeptides or chromatographic separation, and thus serves as a practical alternative to liquid chromatography-electrospray ionization MS. The signature peptides are biomarkers of CDG.
