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

Authors :
Kodríková R
Pakanová Z
Krchňák M
Šedivá M
Šesták S
Květoň F
Beke G
Šalingová A
Skalická K
Brennerová K
Jančová E
Baráth P
Mucha J
Nemčovič M
Source :
Biomedicines [Biomedicines] 2023 Feb 16; Vol. 11 (2). Date of Electronic Publication: 2023 Feb 16.
Publication Year :
2023

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.

Details

Language :
English
ISSN :
2227-9059
Volume :
11
Issue :
2
Database :
MEDLINE
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
36831116
Full Text :
https://doi.org/10.3390/biomedicines11020580