Mass spectrometry glycophenotype characterization of ALG2-CDG in Argentinean patients with a new genetic variant in homozygosis.
Glycoconj J
; 38(2): 191-200, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33644825
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos
/
Defeitos Congênitos da Glicosilação
/
Manosiltransferases
Limite:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
País/Região como assunto:
America do sul
/
Argentina
Idioma:
En
Revista:
Glycoconj J
Assunto da revista:
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Argentina