MAN1B1 Deficiency: An Unexpected CDG-II

• Autores: Rymen, Daisy; Peanne, Romain; Millón, María Beatriz; Race, Valérie; Sturiale, Luisa; Garozzo, Domenico; Mills, Philippa; Clayton, Peter; Asteggiano, Carla Gabriela; Quelhas, Dulce; Cansu, Ali; Martins, Esmeralda; Nassogne, Marie-Cécile; Gonçalves-Rocha, Miguel; Topaloglu, Haluk; Jaeken, Jaak; Foulquier, François; Matthijs, Gert
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Glycosylation; Congenital Disorders of Glycosylation; MAN1B1 gene; CDG Type II
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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 CDGII 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.
Fil: Rymen, Daisy. Center for Human Genetics. Katholikie Universiteit Leuven; Bélgica; University Hospital Gasthuisberg . Center for Metabolic Diseases; Bélgica;
Fil: Peanne, Romain. Center for Human Genetics. Katholikie Universiteit Leuven; Bélgica;
Fil: Millón, María Beatriz. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina;
Fil: Race, Valérie. Center for Human Genetics. Katholikie Universiteit Leuven; Bélgica;
Fil: Sturiale, Luisa. Institute of Chemistry and Technology of Polymers, CNR, Italia;
Fil: Garozzo, Domenico. Institute of Chemistry and Technology of Polymers, CNR, Italia;
Fil: Mills, Philippa. Hospital for Children NHS Trust. Clinical & Molecular Genetics Unit. Institute of Child Health; United Kingdom;
Fil: Clayton, Peter. Hospital for Children NHS Trust. Clinical & Molecular Genetics Unit. Institute of Child Health; United Kingdom;
Fil: Asteggiano, Carla Gabriela. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina;
Fil: Quelhas, Dulce. Centro de Genética Medica - Dr. Jacinto Magalhaes - INSA. Unidad de Genética Médica. Departamento de Genética Humana; Portugal;
Fil: Cansu, Ali. Gazi University Faculty of Medicine, Department of Paediatric Neurology; Turkey;
Fil: Martins, Esmeralda. Hospital de Criancas Maria Pia. Unidade de Doencas Metabólicas; Portugal;
Fil: Nassogne, Marie-Cécile. Cliniques Universitaires Saint-Luc. Universite Catholique de Louvain; Bélgica;
Fil: Gonçalves-Rocha, Miguel. Centro de Genética Medica - Dr. Jacinto Magalhaes - INSA. Unidad de Genética Médica. Departamento de Genética Humana; Portugal;
Fil: Topaloglu, Haluk. Hacettepe University Children’s Hospital . Department of Child Neurology. AnkarA: Turquía;
Fil: Jaeken, Jaak. University Hospital Gasthuisberg . Center for Metabolic Diseases; Bélgica;
Fil: Foulquier, François. University of Lille 1. Structural and Functional Glycobiology Unit.; Francia;
Fil: Matthijs, Gert. Center for Human Genetics. Katholikie Universiteit Leuven; Bélgica;