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

• Published in: Nature medicine Vol. 10; no. 5; pp. 518 - 523
• Main Authors: Freeze, Hudson H, Wu, Xiaohua, Steet, Richard A, Bohorov, Ognian, Bakker, Jaap, Newell, John, Krieger, Monty, Spaapen, Leo, Kornfeld, Stuart
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.05.2004
• Subjects: Base Sequence; Biosynthesis; Carbohydrate Metabolism, Inborn Errors - genetics; Carbohydrate Metabolism, Inborn Errors - metabolism; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; DNA, Complementary - genetics; Female; Glycosylation; Golgi Apparatus - metabolism; Homozygote; Humans; Infant; Infant, Newborn; Male; Mutation; Siblings
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm1041

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.