Serum N-glycomics of a novel CDG-IIb patient reveals aberrant IgG glycosylation

Glycobiology. 2022 Apr 21;32(5):380-390. doi: 10.1093/glycob/cwac003.


Rare genetic mutations of the mannosyl-oligosaccharide glucosidase (MOGS) gene affecting the function of the mannosyl-oligosaccharide glucosidase (glucosidase I) are the cause of the congenital disorder of glycosylation IIb (CDG-IIb). Glucosidase I specifically removes the distal α1,2-linked glucose from the protein bound precursor N-glycan Glc3Man9GlcNAc2, which is the initial step of N-glycan maturation. Here, we comparatively analyzed N-glycosylation of the whole serum proteome, serum-derived immunoglobulin G (IgG), transferrin (TF), and α-1-antitrypsin (AAT) of a female patient who is compound heterozygous for 2 novel missense mutations in the MOGS gene, her heterozygous parents, and a sibling with wildtype genotype by multiplexed capillary gel electrophoresis coupled to laser induced fluorescence detection (xCGE-LIF) at unprecedented depth. Thereby, we detected the CDG-IIb-characteristic non-de-glucosylated N-glycans Glc3Man7-9GlcNAc2 as well as the free tetrasaccharide Glc3-Man in whole serum of the patient but not in the other family members. The N-glycan analysis of the serum proteome further revealed that relative intensities of IgG-specific complex type di-antennary N-glycans with core-fucosylation were considerably reduced in the patient's serum whereas TF- and AAT-characteristic sialylated di- and tri-antennary N-glycans were increased. This finding reflected the hypogammaglobulinemia diagnosed in the patient. We further detected aberrant oligo-mannose (Glc3Man7GlcNAc2) and hybrid type N-glycans on patient-derived IgGs and we attributed this defective glycosylation to be the reason for an increased IgG clearance. This mechanism can explain the hypogammaglobulinemia that is associated with CDG-IIb.

Keywords: N-glycosylation; CDG-IIb; CGE-LIF; glycomics; immunoglobulin G (IgG).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinemia*
  • Congenital Disorders of Glycosylation* / genetics
  • Congenital Disorders of Glycosylation* / metabolism
  • Female
  • Glycomics
  • Glycosylation
  • Humans
  • Immunoglobulin G / metabolism
  • Polysaccharides / metabolism
  • Proteome / metabolism


  • Immunoglobulin G
  • Polysaccharides
  • Proteome