Mass spectrometry glycophenotype characterization of ALG2-CDG in Argentinean patients with a new genetic variant in homozygosis
| Autor: | Belén Pérez, Marisa Cubilla, Gabriela Magali Papazoglu, Raquel Dodelson de Kremer, Luisa Sturiale, Marcela Pereyra, C. G. Asteggiano |
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| Přispěvatelé: | Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Universidad Católica de Córdoba, Ministerio de Salud de la Nación (Argentina) |
| Rok vydání: | 2021 |
| Předmět: |
Glycan
congenital hereditary and neonatal diseases and abnormalities Glycosylation Alpha-1 3-mannosyltransferase Biochemistry 3-mannosyltransferase ALG2-CDG 03 medical and health sciences chemistry.chemical_compound Alpha-1 Glycophenotype medicine Missense mutation Congenital disorders of glycosylation Molecular Biology Exome sequencing 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Mass spectrometry 030302 biochemistry & molecular biology Cell Biology medicine.disease Molecular biology Phenotype Congenital myasthenic syndromes carbohydrates (lipids) chemistry Transferrin Mannosylation biology.protein Congenital disorder of glycosylation |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Glycoconjugate journal 38 (2021): 191–200. doi:10.1007/s10719-021-09976-w info:cnr-pdr/source/autori:Magali Papazoglu, Gabriela; Cubilla, Marisa; Pereyra, Marcela; de Kremer, Raquel Dodelson; Perez, Belen; Sturiale, Luisa; Gabriela Asteggiano, Carla/titolo:Mass spectrometry glycophenotype characterization of ALG2-CDG in Argentinean patients with a new genetic variant in homozygosis/doi:10.1007%2Fs10719-021-09976-w/rivista:Glycoconjugate journal/anno:2021/pagina_da:191/pagina_a:200/intervallo_pagine:191–200/volume:38 |
| DOI: | 10.1007/s10719-021-09976-w |
| Popis: | Human ALG2 encodes an α 1,3mannosyltransferase that catalyzes the first steps in the synthesis of N-glycans in the endoplasmic reticulum. Variants in ALG2cause a congenital disorder of glycosylation (CDG) known as ALG2-CDG. Up to date, nine ALG2-CDG patients have been reported worldwide. ALG2-CDG is a rare autosomal recessive inherited disorder characterized by neurological involvement, convulsive syndrome of unknown origin, axial hypotonia, and mental and motor regression. In this study, we used MALDI-TOF MS to define both total serum protein and transferrin (Tf) N-glycan phenotypes in three ALG2-CDG patients carrying a c.752G > T, p.Arg251Leu ALG2 missense variant in homozygous state, as determined by exome sequencing. Comparing it to control samples, we have observed Tf under-occupancy of glycosylation site(s) typical of a defective N-glycan assembly and the occurrence of oligomannose and hybrid type N-glycans. Moreover, we have observed a slight oligomannose accumulation in total serum glyco-profiles. The increased heterogeneity of serum N-glycome in the studied patients suggests a marginal disarrangement of the glycan processing in ALG2-CDG. Previous studies reported on slightly increased concentrations of abnormal serum N-glycans in CDG-I due to defects in the mannosylation steps of dolichol-linked oligosaccharide biosynthesis. This preliminary work aims at considering serum N-glycan accumulation of high mannosylated glycoforms, such as oligomannose and hybrid type N-glycans, as potential diagnostic signals for ALG2-CDG patients. CONICET 2017–2021 (RD: 2191), MinCyT FONCyT PICT2010–2824/PID Clinic 2018; Universidad Católica de Córdoba 2015–2019, and the National Health Department of Argentina |
| Databáze: | OpenAIRE |
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