Deficiency in COG5 causes a moderate form of congenital disorders of glycosylation
| Autor: | Thierry Hennet, Siegrun Schnabel, Patricie Paesold-Burda, Heinz Troxler, Matthias R. Baumgartner, Peter Kleinert, Charlotte Maag, François Foulquier |
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| Přispěvatelé: | University of Zurich, Paesold-Burda, P, University Children's Hospital, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Department of General Pediatrics, Münster University Children Hospital, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
2716 Genetics (clinical)
Glycosylation Adolescent RNA Splicing 610 Medicine & health Biology medicine.disease_cause 10052 Institute of Physiology 03 medical and health sciences chemistry.chemical_compound Exon symbols.namesake 0302 clinical medicine Cog 1311 Genetics Genetics medicine 1312 Molecular Biology Humans [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Child Molecular Biology Genetics (clinical) Secretory pathway Cells Cultured 030304 developmental biology 0303 health sciences Mutation Conserved oligomeric Golgi complex General Medicine Golgi apparatus Fibroblasts Exon skipping [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Cell biology Adaptor Proteins Vesicular Transport chemistry 10036 Medical Clinic 10076 Center for Integrative Human Physiology symbols 570 Life sciences biology Female 030217 neurology & neurosurgery Metabolism Inborn Errors |
| Zdroj: | Human Molecular Genetics Human Molecular Genetics, Oxford University Press (OUP), 2009, epub ahead of print. ⟨10.1093/hmg/ddp389⟩ Human Molecular Genetics, 2009, epub ahead of print. ⟨10.1093/hmg/ddp389⟩ |
| ISSN: | 0964-6906 1460-2083 |
| DOI: | 10.5167/uzh-25739 |
| Popis: | International audience; The conserved oligomeric Golgi (COG) complex is a tethering factor composed of eight subunits that is involved in the retrograde transport of intra-Golgi components. Deficient biosynthesis of COG subunits leads to alterations of protein trafficking along the secretory pathway and thereby to severe diseases in humans. Since the COG complex affects the localization of several Golgi glycosyltransferase enzymes, COG deficiency also leads to defective protein glycosylation, thereby explaining the classification of COG deficiencies as forms of congenital disorder of glycosylation (CDG). To date, mutations in COG1, COG4, COG7 and COG8 genes have been associated with diseases, which range from severe multi-organ disorders to moderate forms of neurological impairment. In the present study, we describe a new type of COG deficiency related to a splicing mutation in the COG5 gene. Sequence analysis in the patient identified a homozygous intronic substitution (c.1669-15T>C) leading to exon skipping and severely reduced expression of the COG5 protein. This defect was associated with a mild psychomotor retardation with delayed motor and language development. Analysis of different serum glycoproteins revealed a CDG phenotype with typical undersialylation of N- and O-glycans. Retrograde Golgi-to-endoplasmic reticulum trafficking was markedly delayed in the patient's fibroblast upon brefeldin-A treatment, which is a hallmark of COG deficiency. This trafficking delay could be restored to normal values by expressing a wildtype COG5 cDNA in the patient cells. This case demonstrates that COG deficiency and thereby CDG must be taken into consideration even in children presenting mild neurological impairments. |
| Databáze: | OpenAIRE |
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