Life with too much polyprenol: polyprenol reductase deficiency
| Autor: | Sabine Rudnik-Schöneborn, Martin Häusler, B. Müller, J.E.H. Gründahl, I. Du Chesne, N. Ortiz-Brüchle, Stephan Rust, Ewa Swiezewska, Thorsten Marquardt, J. Siedlecka, Ziqiang Guan, Janine Reunert, Christian R. H. Raetz, Klaus Zerres |
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| Rok vydání: | 2012 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Glycan Glycosylation Polyprenol reductase Endocrinology Diabetes and Metabolism Biology Biochemistry Article chemistry.chemical_compound Polyprenol Congenital Disorders of Glycosylation Pentanols Endocrinology Dolichol 3-Oxo-5-alpha-Steroid 4-Dehydrogenase Biosynthesis Dolichols Genetics Humans Immunoprecipitation Molecular Biology Cells Cultured Chromatography High Pressure Liquid chemistry.chemical_classification Genetic Complementation Test Homozygote Infant Newborn Membrane Proteins Fibroblasts Pedigree carbohydrates (lipids) chemistry Transferrin Mutation biology.protein Electrophoresis Polyacrylamide Gel Female lipids (amino acids peptides and proteins) Isoelectric Focusing Glycoprotein |
| Zdroj: | Molecular Genetics and Metabolism. 105:642-651 |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2011.12.017 |
| Popis: | Congenital disorders of glycosylation (CDG) are caused by a dysfunction of glycosylation, an essential step in the manufacturing process of glycoproteins. This paper focuses on a 6-year-old patient with a new type of CDG-I caused by a defect of the steroid 5α reductase type 3 gene (SRD5A3). The clinical features were psychomotor retardation, pathological nystagmus, slight muscular hypotonia and microcephaly. SRD5A3 was recently identified encoding the polyprenol reductase, an enzyme catalyzing the final step of the biosynthesis of dolichol, which is required for the assembly of the glycans needed for N-glycosylation. Although an early homozygous stop-codon (c.57G>A [W19X]) with no functional protein was found in the patient, about 70% of transferrin (Tf) was correctly glycosylated. Quantification of dolichol and unreduced polyprenol in the patient's fibroblasts demonstrated a high polyprenol/dolichol ratio with normal amounts of dolichol, indicating that high polyprenol levels might compete with dolichol for the initiation of N-glycan assembly but without supporting normal glycosylation and that there must be an alternative pathway for dolichol biosynthesis. |
| Databáze: | OpenAIRE |
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