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<i>N</i>-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant
oleh: Rebeka Kodríková, Zuzana Pakanová, Maroš Krchňák, Mária Šedivá, Sergej Šesták, Filip Květoň, Gábor Beke, Anna Šalingová, Katarína Skalická, Katarína Brennerová, Emília Jančová, Peter Baráth, Ján Mucha, Marek Nemčovič
Format: | Article |
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Diterbitkan: | MDPI AG 2023-02-01 |
Deskripsi
Congenital disorders of glycosylation (CDG) are a group of rare inherited metabolic disorders caused by a defect in the process of protein glycosylation. In this work, we present a comprehensive glycoprofile analysis of a male patient with a novel missense variant in the <i>SLC35A2</i> gene, coding a galactose transporter that translocates UDP-galactose from the cytosol to the lumen of the endoplasmic reticulum and Golgi apparatus. Isoelectric focusing of serum transferrin, which resulted in a CDG type II pattern, was followed by structural analysis of transferrin and serum <i>N</i>-glycans, as well as the analysis of apolipoprotein CIII <i>O</i>-glycans by mass spectrometry. An abnormal serum <i>N</i>-glycoprofile with significantly increased levels of agalactosylated (Hex3HexNAc4-5 and Hex3HexNAc5Fuc1) and monogalactosylated (Hex4HexNAc4 ± NeuAc1) <i>N</i>-glycans was observed. Additionally, whole exome sequencing and Sanger sequencing revealed de novo hemizygous c.461T > C (p.Leu154Pro) mutation in the <i>SLC35A2</i> gene. Based on the combination of biochemical, analytical, and genomic approaches, the set of distinctive <i>N</i>-glycan biomarkers was characterized. Potentially, the set of identified aberrant <i>N</i>-glycans can be specific for other variants causing SLC35A2-CDG and can distinguish this disorder from the other CDGs or other defects in the galactose metabolism.