N-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant

Author:

Kodríková Rebeka1ORCID,Pakanová Zuzana1,Krchňák Maroš1,Šedivá Mária1,Šesták Sergej1ORCID,Květoň Filip1ORCID,Beke Gábor12,Šalingová Anna3,Skalická Katarína4,Brennerová Katarína5,Jančová Emília5,Baráth Peter1ORCID,Mucha Ján1,Nemčovič Marek1

Affiliation:

1. Institute of Chemistry, Centre of Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, Slovakia

2. Department of Genomics and Biotechnology, Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava, Slovakia

3. National Institute of Children’s Diseases, Center for Inherited Metabolic Disorders, Limbová 1, 833 40 Bratislava, Slovakia

4. Laboratory of Clinical and Molecular Genetics, National Institute of Children’s Diseases, Limbová 1, 833 40 Bratislava, Slovakia

5. Department of Paediatrics, Faculty of Medicine of Comenius University and National Institute for Children’s Diseases, Limbová 1, 833 40 Bratislava, Slovakia

Abstract

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 SLC35A2 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 N-glycans, as well as the analysis of apolipoprotein CIII O-glycans by mass spectrometry. An abnormal serum N-glycoprofile with significantly increased levels of agalactosylated (Hex3HexNAc4-5 and Hex3HexNAc5Fuc1) and monogalactosylated (Hex4HexNAc4 ± NeuAc1) N-glycans was observed. Additionally, whole exome sequencing and Sanger sequencing revealed de novo hemizygous c.461T > C (p.Leu154Pro) mutation in the SLC35A2 gene. Based on the combination of biochemical, analytical, and genomic approaches, the set of distinctive N-glycan biomarkers was characterized. Potentially, the set of identified aberrant N-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.

Funder

Ministry of Health of the Slovak Republic

European Regional Development Fund

MetabERN

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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