MAN1B1-CDG: Three new individuals and associated biochemical profiles.
Soraya Sakhi, Sophie Cholet, Samer Wehbi, Bertrand Isidor, Benjamin Cogne, Sandrine Vuillaumier-Barrot, Thierry Dupré, Trost Detleft, Emmanuelle Schmitt, Bruno Leheup, Céline Bonnet, François Feillet, Christine Muti, François Fenaille, Arnaud Bruneel
Author Information
Soraya Sakhi: AP-HP, Biochimie Métabolique et Cellulaire, Hôpital Bichat-Claude Bernard, Paris, France.
Sophie Cholet: Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB, F-91191 Gif sur Yvette, France.
Samer Wehbi: Service de Pédiatrie, Centre hospitalier de Versailles, Le Chesnay, France.
Bertrand Isidor: Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 44093 Nantes, France.
Benjamin Cogne: Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 44093 Nantes, France.
Sandrine Vuillaumier-Barrot: AP-HP, Biochimie Métabolique et Cellulaire, Hôpital Bichat-Claude Bernard, Paris, France.
Thierry Dupré: AP-HP, Biochimie Métabolique et Cellulaire, Hôpital Bichat-Claude Bernard, Paris, France.
Trost Detleft: Laboratoire CERBA, 95310 Saint-Ouen l'Aumone, France.
Emmanuelle Schmitt: Service de Neuroradiologie Diagnostique et Thérapeutique, Centre Hospitalier Universitaire de Nancy, Nancy, France.
Bruno Leheup: Centre de Référence Syndromes Malformatifs et Anomalies du Développement - Service de Génétique Clinique, Centre Hospitalier Universitaire de Nancy, F-54000 Nancy, France.
Céline Bonnet: Laboratoire de Génétique, Centre Hospitalier Universitaire de Nancy, F-54000 Nancy, France.
François Feillet: Reference Center for Inborn Errors of Metabolism, University Hospital of Nancy, F-54000 Nancy, France.
Christine Muti: Unité de Génétique Constitutionnelle, Service de Biologie, Centre Hospitalier de Versailles, Le Chesnay, France.
François Fenaille: Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB, F-91191 Gif sur Yvette, France.
Arnaud Bruneel: AP-HP, Biochimie Métabolique et Cellulaire, Hôpital Bichat-Claude Bernard, Paris, France.
Congenital disorders of glycosylation (CDG) constitute an ever-growing group of genetic diseases affecting the glycosylation of proteins. CDG individuals usually present with severe multisystem disorders. MAN1B1-CDG is a CDG with nonspecific clinical symptoms such as intellectual deficiency and developmental delay. Although up to 40 affected individuals were described so far, its final diagnosis is not straightforward using common biochemical methods due to the trace-level accumulation of defective glycan structures. In this study, we present three unreported MAN1B1-CDG individuals and propose a decision tree to reach diagnosis using a panel of techniques ranging from exome sequencing to gel electrophoresis and mass spectrometry. The occurrence of MAN1B1-CDG in patients showing unexplained intellectual disability and development delay, as well as a particular transferrin glycosylation profile, can be ascertained notably using matrix assisted laser desorption/ionization - time of flight (MALDI-TOF) mass spectrometry analysis of -β-acetylglucosaminidase H-released serum N-glycans. In addition to reporting new pathogenic variants and additional clinical signs such as hypersialorrhea, we highlight particular biochemical features of MAN1B1-CDG with potential glycoprotein-specific glycosylation defects.
