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Article
Nature Medicine  10, 518 - 523 (2004)
Published online: 25 April 2004; | doi:10.1038/nm1041

Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder

Xiaohua Wu1, 6, Richard A Steet2, 6, Ognian Bohorov1, Jaap Bakker3, John Newell1, 5, Monty Krieger4, Leo Spaapen3, Stuart Kornfeld2 & Hudson H Freeze1

1  The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, USA.

2  Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., Saint Louis, Missouri 63110, USA.

3  Department of Clinical Genetics, Academic Hospital Maastricht, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.

4  Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, Massachusetts 02139, USA.

5  Present address: Nestlé Research Center, Nestec Ltd., Vers−chez−les−Blanc, CH−1000 Lausanne 26, Switzerland.

6  These authors contributed equally to this work.

Correspondence should be addressed to Hudson H Freeze hudson@burnham.org
The congenital disorders of glycosylation (CDG) are characterized by defects in N-linked glycan biosynthesis that result from mutations in genes encoding proteins directly involved in the glycosylation pathway. Here we describe two siblings with a fatal form of CDG caused by a mutation in the gene encoding COG-7, a subunit of the conserved oligomeric Golgi (COG) complex. The mutation impairs integrity of the COG complex and alters Golgi trafficking, resulting in disruption of multiple glycosylation pathways. These cases represent a new type of CDG in which the molecular defect lies in a protein that affects the trafficking and function of the glycosylation machinery.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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