Titre :

MAN1B1 deficiency: an unexpected CDG-II

Auteur(s) :

Rymen, Daisy [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Péanne, Romain [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Millón, María B. [Auteur]
Universidad Nacional de Córdoba [Argentina]
Race, Valérie [Auteur]
Center for Human Genetics, University of Leuven School of Medicine
Sturiale, Luisa [Auteur]

Garozzo, Domenico [Auteur]

Mills, Philippa [Auteur]
Institute of Child Health [London]
Clayton, Peter [Auteur]
Institute of Child Health [London]
Asteggiano, Carla G. [Auteur]
Universidad Nacional de Córdoba [Argentina]
Quelhas, Dulce [Auteur]
Faculdade de Medicina da Universidade do Porto [FMUP]
Cansu, Ali [Auteur]
Ankara University School of Medicine [Turkey]
Martins, Esmeralda [Auteur]
Faculdade de Medicina da Universidade do Porto [FMUP]
Nassogne, Marie-Cécile [Auteur]
Cliniques Universitaires Saint-Luc [Bruxelles]
Gonçalves-Rocha, Miguel [Auteur]
Faculdade de Medicina da Universidade do Porto [FMUP]
Topaloglu, Haluk [Auteur]
Hacettepe University = Hacettepe Üniversitesi
Jaeken, Jaak [Auteur]
University Hospital Gasthuisberg [Leuven]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Matthijs, Gert [Auteur]
Center for Human Genetics, University of Leuven School of Medicine

Titre de la revue :

PLoS genetics

Nom court de la revue :

PLoS Genet.

Numéro :

9

Pagination :

e1003989

Date de publication :

2013

ISSN :

1553-7404

Mot(s)-clé(s) en anglais :

Amino Acid Sequence
Genetic Association Studies
Mannosidases
Humans
Male
Infant
Glycosylation
Exome
Golgi Apparatus
Congenital Disorders of Glycosylation
Adolescent
Female
High-Throughput Nucleotide Sequencing
Mutation
Child
Intellectual Disability

Discipline(s) HAL :

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. In the present study, exome sequencing was used to identify MAN1B1 as the culprit gene ...
Lire la suite >Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. In the present study, exome sequencing was used to identify MAN1B1 as the culprit gene in an unsolved CDG-II patient. Subsequently, 6 additional cases with MAN1B1-CDG were found. All individuals presented slight facial dysmorphism, psychomotor retardation and truncal obesity. Generally, MAN1B1 is believed to be an ER resident alpha-1,2-mannosidase acting as a key factor in glycoprotein quality control by targeting misfolded proteins for ER-associated degradation (ERAD). However, recent studies indicated a Golgi localization of the endogenous MAN1B1, suggesting a more complex role for MAN1B1 in quality control. We were able to confirm that MAN1B1 is indeed localized to the Golgi complex instead of the ER. Furthermore, we observed an altered Golgi morphology in all patients' cells, with marked dilatation and fragmentation. We hypothesize that part of the phenotype is associated to this Golgi disruption. In conclusion, we linked mutations in MAN1B1 to a Golgi glycosylation disorder. Additionally, our results support the recent findings on MAN1B1 localization. However, more work is needed to pinpoint the exact function of MAN1B1 in glycoprotein quality control, and to understand the pathophysiology of its deficiency.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

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 :

2020-02-12T15:12:07Z
2021-03-04T14:06:15Z