Titre :

Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype

Auteur(s) :

Blommaert, Eline [Auteur]
Péanne, Romain [Auteur]
Cherepanova, Natalia A. [Auteur]
Rymen, Daisy [Auteur]
Staels, Frederik [Auteur]
Jaeken, Jaak [Auteur]
Race, Valérie [Auteur]
Keldermans, Liesbeth [Auteur]
Souche, Erika [Auteur]
Corveleyn, Anniek [Auteur]
Sparkes, Rebecca [Auteur]
Bhattacharya, Kaustuv [Auteur]
Devalck, Christine [Auteur]
Schrijvers, Rik [Auteur]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Gilmore, Reid [Auteur]
Matthijs, Gert [Auteur]

Titre de la revue :

Proceedings of the National Academy of Sciences

Nom court de la revue :

Proc Natl Acad Sci USA

Numéro :

116

Pagination :

9865-9870

Éditeur :

Proceedings of the National Academy of Sciences

Date de publication :

2019-04-29

Mot(s)-clé(s) en anglais :

congenital disorders of glycosylation
CDG
XMEN
oligosaccharyltransferase complex

Discipline(s) HAL :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. We identified two patients with defective serum transferrin glycosylation and mutations ...
Lire la suite >Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. We identified two patients with defective serum transferrin glycosylation and mutations in the MAGT1 gene. These patients present with a phenotype that is mainly characterized by intellectual and developmental disability. MAGT1 has been described to be a subunit of the oligosaccharyltransferase (OST) complex and more specifically of the STT3B complex. However, it was also claimed that MAGT1 is a magnesium (Mg2+) transporter. So far, patients with mutations in MAGT1 were linked to a primary immunodeficiency, characterized by chronic EBV infections attributed to a Mg2+ homeostasis defect (XMEN). We compared the clinical and cellular phenotype of our two patients to that of an XMEN patient that we recently identified. All three patients have an N-glycosylation defect, as was shown by the study of different substrates, such as GLUT1 and SHBG, demonstrating that the posttranslational glycosylation carried out by the STT3B complex is dysfunctional in all three patients. Moreover, MAGT1 deficiency is associated with an enhanced expression of TUSC3, the homolog protein of MAGT1, pointing toward a compensatory mechanism. Hence, we delineate MAGT1-CDG as a disorder associated with two different clinical phenotypes caused by defects in glycosylation.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Mécanismes moléculaires de la N-glycosylation et pathologies associées

Date de dépôt :

2020-12-18T13:52:32Z
2021-01-04T10:46:06Z
2021-01-07T14:00:06Z