MALDI‐MS profiling of serum O‐glycosylation and N‐glycosylation in COG5‐CDG

• Published in: Journal of mass spectrometry. 2017-06, Vol.52 (6), p.372-377
• Main Authors: Palmigiano, A., Bua, R. O., Barone, R., Rymen, D., Régal, L., Deconinck, N., Dionisi‐Vici, C., Fung, C.‐W., Garozzo, D., Jaeken, J., Sturiale, L.
• Format: Article
• Language: English
• Subjects: Abnormalities; Abundance; Adaptor Proteins, Vesicular Transport - blood; apoC‐III IEF; Apolipoprotein C-III; Autism; Biomarkers - blood; Case-Control Studies; Child; COG5‐CDG; Congenital Disorders of Glycosylation - blood; Congenital Disorders of Glycosylation - diagnosis; Defects; Desorption; Diagnosis; Diseases; Disorders; Glycan; Glycoconjugates; Glycosylation; Golgi apparatus; High-throughput screening; High-Throughput Screening Assays - methods; Humans; Impairment; Ionization; Ions; Isoelectric focusing; Lasers; MALDI‐TOF; Malformations; Mannose; Microencephaly; N‐glycosylation; O‐glycosylation; Patients; Polysaccharides; Polysaccharides - blood; Profiling; Relative abundance; Screening; Seizing; Seizures; Separation; Serum; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structures; Transferrin; Transferrins
• ISSN: 1076-5174; 1096-9888
• DOI: 10.1002/jms.3936

Congenital disorders of glycosylation (CDG) are due to defective glycosylation of glycoconjugates. Conserved oligomeric Golgi (COG)‐CDG are genetic diseases due to defects of the COG complex subunits 1–8 causing N‐glycan and O‐glycan processing abnormalities. In COG‐CDG, isoelectric focusing separation of undersialylated glycoforms of serum transferrin and apolipoprotein C‐III (apoC‐III) allows to detect N‐glycosylation and O‐glycosylation defects, respectively. COG5‐CDG (COG5 subunit deficiency) is a multisystem disease with dysmorphic features, intellectual disability of variable degree, seizures, acquired microcephaly, sensory defects and autistic behavior. We applied matrix‐assisted laser desorption/ionization‐MS for a high‐throughput screening of differential serum O‐glycoform and N‐glycoform in five patients with COG5‐CDG. When compared with age‐matched controls, COG5‐CDG showed a significant increase of apoC‐III0a (aglycosylated glycoform), whereas apoC‐III1 (mono‐sialylated glycoform) decreased significantly. Serum N‐glycome of COG5‐CDG patients was characterized by the relative abundance of undersialylated and undergalactosylated biantennary and triantennary glycans as well as slight increase of high‐mannose structures and hybrid glycans. Using advanced and well‐established MS‐based approaches, the present findings reveal novel aspects on O‐glycan and N‐glycan profiling in COG5‐CDG patients, thus providing an increase of current knowledge on glycosylation defects caused by impairment of COG subunits, in support of clinical diagnosis. Copyright © 2017 John Wiley & Sons, Ltd.