A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis.

N-glycosylation congenital disorders of glycosylation dolichal dolichol lipid droplets polyisoprenoids polyprenal polyprenol pseudoautosomal region

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
22 May 2024
Historique:
received: 12 07 2023
revised: 21 02 2024
accepted: 29 04 2024
medline: 1 6 2024
pubmed: 1 6 2024
entrez: 31 5 2024
Statut: aheadofprint

Résumé

Dolichol is a lipid critical for N-glycosylation as a carrier for activated sugars and nascent oligosaccharides. It is commonly thought to be directly produced from polyprenol by the enzyme SRD5A3. Instead, we found that dolichol synthesis requires a three-step detour involving additional metabolites, where SRD5A3 catalyzes only the second reaction. The first and third steps are performed by DHRSX, whose gene resides on the pseudoautosomal regions of the X and Y chromosomes. Accordingly, we report a pseudoautosomal-recessive disease presenting as a congenital disorder of glycosylation in patients with missense variants in DHRSX (DHRSX-CDG). Of note, DHRSX has a unique dual substrate and cofactor specificity, allowing it to act as a NAD

Identifiants

DOI: 10.1016/j.cell.2024.04.041 PMID: 38821050
pubmed: 38821050
pii: S0092-8674(24)00467-7
doi: 10.1016/j.cell.2024.04.041
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Matthew P Wilson (MP)

Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven, Leuven, Belgium.

Takfarinas Kentache (T)

Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium.

Charlotte R Althoff (CR)

Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven, Leuven, Belgium; Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.

Céline Schulz (C)

Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.

Geoffroy de Bettignies (G)

Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.

Gisèle Mateu Cabrera (G)

Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven, Leuven, Belgium.

Loreta Cimbalistiene (L)

Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.

Birute Burnyte (B)

Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.

Grace Yoon (G)

Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Canada; Division of Neurology, Hospital for Sick Children, Toronto, Canada; Department of Paediatrics, University of Toronto, Toronto, Canada.

Gregory Costain (G)

Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Canada; Department of Paediatrics, University of Toronto, Toronto, Canada; Program in Genetics and Genome Biology, SickKids Research Institute, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada.

Sandrine Vuillaumier-Barrot (S)

AP-HP, Biochimie Métabolique et Cellulaire and Département de Génétique, Hôpital Bichat-Claude Bernard, and Université de Paris, Faculté de Médecine Xavier Bichat, INSERM U1149, CRI, Paris, France.

David Cheillan (D)

Service Biochimie et Biologie Moléculaire - Hospices Civils de Lyon; Laboratoire Carmen - Inserm U1060, INRAE UMR1397, Université Claude Bernard Lyon 1, Lyon, France.

Daisy Rymen (D)

Department of Pediatrics, Center for Metabolic Diseases, University Hospitals Leuven, Leuven, Belgium.

Lucie Rychtarova (L)

Laboratory for Study of Mitochondrial Disorders, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czechia.

Hana Hansikova (H)

Laboratory for Study of Mitochondrial Disorders, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czechia.

Marina Bury (M)

Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium.

Joseph P Dewulf (JP)

Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium.

Francesco Caligiore (F)

Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium.

Jaak Jaeken (J)

Department of Pediatrics, Center for Metabolic Diseases, University Hospitals Leuven, Leuven, Belgium.

Vincent Cantagrel (V)

Developmental Brain Disorders Laboratory, Université Paris Cité, INSERM UMR1163, Imagine Institute, Paris, France.

Emile Van Schaftingen (E)

Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium. Electronic address: emile.vanschaftingen@uclouvain.be.

Gert Matthijs (G)

Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven, Leuven, Belgium. Electronic address: gert.matthijs@kuleuven.be.

François Foulquier (F)

Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France. Electronic address: francois.foulquier@univ-lille.fr.

Guido T Bommer (GT)

Metabolic Research Group, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium. Electronic address: guido.bommer@uclouvain.be.

Classifications MeSH