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A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation

Foulquier, F., Ungar, D., Reynders, E., Zeevaert, R., Mills, P., García-Silva, M.T., Briones, P., Winchester, B., Morelle, W., Krieger, M., Annaert, W. and Matthijs, G. (2007) A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation. Human Molecular Genetics, 16 (7). pp. 717-730. ISSN 0964-6906

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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 ß1,4-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).

Item Type: Article
Institution: The University of York
Academic Units: The University of York > Biology (York)
Depositing User: York RAE Import
Date Deposited: 28 May 2009 08:56
Last Modified: 28 May 2009 08:56
Published Version: http://dx.doi.org/10.1093/hmg/ddl476
Status: Published
Publisher: Oxford University Press
Identification Number: 10.1093/hmg/ddl476
URI: http://eprints.whiterose.ac.uk/id/eprint/6272

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