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DC Field | Value | Language |
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dc.contributor.author | Seyda, A | - |
dc.contributor.author | Newbold, RF | - |
dc.contributor.author | Hudson, TJ | - |
dc.contributor.author | Verner, A | - |
dc.contributor.author | MacKay, N | - |
dc.contributor.author | Winter, S | - |
dc.contributor.author | Feigenbaum, A | - |
dc.contributor.author | Malaney, S | - |
dc.contributor.author | Gonzalez-Halphen, D | - |
dc.contributor.author | Cuthbert, AP | - |
dc.coverage.spatial | 11 | en |
dc.date.accessioned | 2009-03-19T13:56:56Z | - |
dc.date.available | 2009-03-19T13:56:56Z | - |
dc.date.issued | 2001 | - |
dc.identifier.citation | American Journal of Human Genetics. 68 (2) 386-396 | en |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/3114 | - |
dc.description.abstract | We have studied cultured skin fibroblasts from three siblings and one unrelated individual, all of whom had fatal mitochondrial disease manifesting soon after birth. After incubation with 1 mM glucose, these four cell strains exhibited lactate/pyruvate ratios that were six times greater than those of controls. On further analysis, enzymatic activities of the pyruvate dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, NADH cytochrome c reductase, succinate dehydrogenase, and succinate cytochrome c reductase were severely deficient. In two of the siblings the enzymatic activity of cytochrome oxidase was mildly decreased (by approximately 50%). Metabolite analysis performed on urine samples taken from these patients revealed high levels of glycine, leucine, valine, and isoleucine, indicating abnormalities of both the glycine-cleavage system and branched-chain alpha-ketoacid dehydrogenase. In contrast, the activities of fibroblast pyruvate carboxylase, mitochondrial aconitase, and citrate synthase were normal. Immunoblot analysis of selected complex III subunits (core 1, cyt c(1), and iron-sulfur protein) and of the pyruvate dehydrogenase complex subunits revealed no visible changes in the levels of all examined proteins, decreasing the possibility that an import and/or assembly factor is involved. To elucidate the underlying molecular defect, analysis of microcell-mediated chromosome-fusion was performed between the present study's fibroblasts (recipients) and a panel of A9 mouse:human hybrids (donors) developed by Cuthbert et al. (1995). Complementation was observed between the recipient cells from both families and the mouse:human hybrid clone carrying human chromosome 2. These results indicate that the underlying defect in our patients is under the control of a nuclear gene, the locus of which is on chromosome 2. A 5-cM interval has been identified as potentially containing the critical region for the unknown gene. This interval maps to region 2p14-2p13. | en |
dc.format.extent | 500007 bytes | - |
dc.format.mimetype | application/txt | - |
dc.language.iso | en | - |
dc.publisher | Elsevier | en |
dc.subject | Amino acids/blood | en |
dc.subject | Animals | en |
dc.subject | Cells Cultured | en |
dc.subject | Chromosome Deletion | en |
dc.subject | Chromosomes, Human, Pair 2/*genetics | en |
dc.subject | Fatal outcome | en |
dc.title | A novel syndrome affecting multiple mitochondrial functions, located by microcell-mediated transfer to chromosome 2p14-2p13 | en |
dc.type | Research Paper | en |
Appears in Collections: | Biological Sciences Dept of Life Sciences Research Papers |
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Embargoed Paper.txt | 204 B | Text | View/Open |
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