Abstract
BackgroundThe Conserved Oligomeric Golgi (COG) complex is involved in the retrograde trafficking of Golgi components, thereby affecting the localization of Golgi glycosyltransferases. Deficiency of a COG-subunit leads to defective protein glycosylation, and thus Congenital Disorders of Glycosylation (CDG). Mutations in subunits 1, 4, 5, 6, 7 and 8 have been associated with CDG-II. The first patient with COG5-CDG was recently described (Paesold-Burda et al. Hum Mol Genet 2009; 18:4350–6). Contrary to most other COG-CDG cases, the patient presented a mild/moderate phenotype, i.e. moderate psychomotor retardation with language delay, truncal ataxia and slight hypotonia.MethodsCDG-IIx patients from our database were screened for mutations in COG5. Clinical data were compared. Brefeldin A treatment of fibroblasts and immunoblotting experiments were performed to support the diagnosis.Results and conclusionWe identified five new patients with proven COG5 deficiency. We conclude that the clinical picture is not always as mild as previously described. It rather comprises a broad spectrum with phenotypes ranging from mild to very severe. Interestingly, on a clinical basis some of the patients present a significant overlap with COG7-CDG, a finding which can probably be explained by subunit interactions at the protein level.
Highlights
The Conserved Oligomeric Golgi (COG) complex is involved in the retrograde trafficking of Golgi components, thereby affecting the localization of Golgi glycosyltransferases
Since at least 200–300 genes are known to be involved in glycosylation (~1% of the human genome), one expects that the knowledge of Congenital Disorders of Glycosylation (CDG) and diagnosis today represents only the tip of the iceberg
General developmental delay and hypotonia was noted after the age of 1 year, with subsequent delays in fine motor and language development
Summary
The Conserved Oligomeric Golgi (COG) complex is involved in the retrograde trafficking of Golgi components, thereby affecting the localization of Golgi glycosyltransferases. Deficiency of a COG-subunit leads to defective protein glycosylation, and Congenital Disorders of Glycosylation (CDG). Contrary to most other COG-CDG cases, the patient presented a mild/moderate phenotype, i.e. moderate psychomotor retardation with language delay, truncal ataxia and slight hypotonia. The importance of the glycosylation pathway is illustrated by a group of diseases termed Congenital Disorders of Glycosylation (CDG). Many types of CDG involving defects in the biosynthesis, transfer and remodelling of the N-glycan have been discovered. Since at least 200–300 genes are known to be involved in glycosylation (~1% of the human genome), one expects that the knowledge of CDG and diagnosis today represents only the tip of the iceberg. Most types of CDG are caused by mutations in genes directly involved in the glycosylation pathway, i.e. glycosyltransferases, glycosidases or nucleotide
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