MAN1B1 Deficiency: An Unexpected CDG-II

• DOI: 10.1371/journal.pgen.1003989
• Publication Date: 2013-12-12T21:31:51Z
• Authors: Daisy Rymen; Romain Peanne; María B. Millón; Valérie Race; Luisa Sturiale; Domenico Garozzo; Philippa Mills; Peter Clayton; Carla G. Asteggiano; Dulce Quelhas; Ali Cansu; Esmeralda Martins; Marie-Cécile Nass...; Miguel Gonçalves-...; Haluk Topaloglu; Jaak Jaeken; François Foulquier; Gert Matthijs
• Keywords: Endoplasmic-reticulum-associated protein degradation

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