Insights Into the Pathological Glycosylation Associated With COG6-CDG.

Background and Aims: Congenital disorders of glycosylation (CDG) are rare diseases caused by defects in protein glycosylation. We present an infant with multisystemic clinical involvement, diagnosed with COG6-CDG. Methods: Serum and transferrin-linked N-glycans, as well as serum and apolipoprotein CIII-linked O-glycans, were analyzed by MALDI mass spectrometry. Mutation analysis was performed by next-generation sequencing. Functional studies assessed COG6 subunit expression, cooperating subunits, and retrograde transport. GlycoWorks RapiFluor-MS-based N-glycan labeling with HPLC-FLD and ESI-Orbitrap mass spectrometry enabled further comprehensive glycoprofile analysis. Results: Aberrant glycosylation typical of combined N- and O-glycosylation defects was detected. Mutation analysis identified a novel homozygous variant in the Conclusion: This study describes a novel COG6 variant leading to complete loss of protein function and major glycosylation abnormalities. Multiomics analysis provided deeper insights into the molecular mechanisms of this rare disease and the function of the