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Serum N-glycomics of a novel CDG-IIb patient reveals aberrant IgG glycosylation.
Beimdiek, Julia; Hennig, René; Burock, Robert; Puk, Oliver; Biskup, Saskia; Rapp, Erdmann; Lesinski-Schiedat, Anke; Buettner, Falk F R; Das, Anibh M.
Affiliation
  • Beimdiek J; Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
  • Hennig R; glyXera GmbH, Brenneckestraße 20, 39120 Magdeburg, Germany.
  • Burock R; glyXera GmbH, Brenneckestraße 20, 39120 Magdeburg, Germany.
  • Puk O; Praxis für Humangenetik, Paul-Ehrlich-Str. 23, 72076 Tuebingen, Germany.
  • Biskup S; Praxis für Humangenetik, Paul-Ehrlich-Str. 23, 72076 Tuebingen, Germany.
  • Rapp E; glyXera GmbH, Brenneckestraße 20, 39120 Magdeburg, Germany.
  • Lesinski-Schiedat A; Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstraße, 39106 Magdeburg, Germany.
  • Buettner FFR; Otorhinolaryngology Department, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
  • Das AM; Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Glycobiology ; 32(5): 380-390, 2022 04 21.
Article in En | MEDLINE | ID: mdl-35137040
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Congenital Disorders of Glycosylation / Agammaglobulinemia Limits: Female / Humans Language: En Journal: Glycobiology Journal subject: BIOQUIMICA Year: 2022 Type: Article Affiliation country: Germany

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Congenital Disorders of Glycosylation / Agammaglobulinemia Limits: Female / Humans Language: En Journal: Glycobiology Journal subject: BIOQUIMICA Year: 2022 Type: Article Affiliation country: Germany