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Title: A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation
Authors: Foulquier, Fran├žois
Ungar, Daniel
Reynders, Ellen
Zeevaert, Renate
Mills, Philippa
García-Silva, Maria Teresa
Briones, Paz
Winchester, Bryan
Morelle, Willy
Krieger, Monty
Annaert, Wim ×
Matthijs, Gert #
Issue Date: Apr-2007
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:16 issue:7 pages:717-730
Abstract: The hetero-octameric conserved oligomeric Golgi (COG) complex is essential for the structure/function of the Golgi apparatus through regulation of membrane trafficking. Here, we describe a patient with a mild form of a congenital disorder of glycosylation type II (CDG-II), which is caused by a homozygous nonsense mutation in the hCOG8 gene. This leads to a premature stop codon resulting in a truncated Cog8 subunit lacking the 76 C-terminal amino acids. Mass spectrometric analysis of the N- and O-glycan structures identified a mild sialylation deficiency. We showed that the molecular basis of this defect in N- and O-glycosylation is caused by the disruption of the Cog1-Cog8 interaction due to truncation. As a result, Cog1 deficiency accompanies the Cog8 deficiency, preventing assembly of the intact, stable complex and resulting in the appearance of smaller subcomplexes. Moreover, levels of beta1,4-galactosytransferase were significantly reduced. The defects in O-glycosylation could be fully restored by transfecting the patient's fibroblasts with full-length Cog8. The Cog8 defect described here represents a novel type of CDG-II, which we propose to name as CDG-IIh or CDG caused by Cog8 deficiency (CDG-II/Cog8).
URI: 
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Section Child - Miscellaneous (-)
Clinical Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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