The mitochondrial DNA transfer RNA(Lys)A-->G(8344) mutation and the syndrome of myoclonic epilepsy with ragged red fibres (MERRF). Relationship of clinical phenotype to proportion of mutant mitochondrial DNA.
| Autoři: | Hammans SR; University Department of Clinical Neurology, Institute of Neurology, London, UK., Sweeney MG, Brockington M, Lennox GG, Lawton NF, Kennedy CR, Morgan-Hughes JA, Harding AE |
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| Zdroj: | Brain : a journal of neurology [Brain] 1993 Jun; Vol. 116 ( Pt 3), pp. 617-32. |
| Způsob vydávání: | Journal Article; Research Support, Non-U.S. Gov't |
| Jazyk: | English |
| Informace o časopise: | Publisher: Oxford University Press Country of Publication: England NLM ID: 0372537 Publication Model: Print Cited Medium: Print ISSN: 0006-8950 (Print) Linking ISSN: 00068950 NLM ISO Abbreviation: Brain Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Oxford University Press Original Publication: London. |
| Výrazy ze slovníku MeSH: | Mutation*, DNA, Mitochondrial/*genetics , MERRF Syndrome/*genetics , RNA, Transfer, Lys/*genetics, Adult ; Aged ; Amino Acid Sequence ; Child ; DNA, Mitochondrial/analysis ; DNA, Mitochondrial/blood ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Muscles/chemistry ; Pedigree ; Phenotype |
| Abstrakt: | The mitochondrial DNA (mtDNA) transfer RNA (tRNA)Lys A-->G(8344) mutation was identified in seven patients. These patients and their relatives were assessed clinically; in one family the mutation was deduced to be present in four generations. The phenotype in index cases was consistent with the syndrome of myoclonic epilepsy with ragged red fibres, with the core clinical features of myoclonus, ataxia and seizures. Amongst other features, progressive external ophthalmoplegia, Leigh's syndrome and stroke-like episodes were observed, well recognized in mitochondrial myopathies but novel manifestations of this genotype. Samples of blood and muscle were analysed for the proportion of mutant mtDNA using an oligonucleotide hybridization technique. The proportion of mutant mtDNA in blood was significantly greater in symptomatic than asymptomatic cases. Furthermore, the proportion of mutant mtDNA in blood correlated with age of onset of disease and clinical severity assessed by a simple scale. Study of disease associated with the tRNA(Lys) A-->G(8344) mutation provides further insight into the pathogenesis and transmission of mitochondrial diseases. Quantification of the proportion of mtDNA in tissues demonstrates that this is a major factor determining the course of disease, but other, as yet unidentified factors are also likely to play a role. |
| Substance Nomenclature: | 0 (DNA, Mitochondrial) 0 (RNA, Transfer, Lys) |
| Entry Date(s): | Date Created: 19930601 Date Completed: 19930721 Latest Revision: 20190512 |
| Update Code: | 20240829 |
| DOI: | 10.1093/brain/116.3.617 |
| PMID: | 8513395 |
| Autor: | Hammans SR; University Department of Clinical Neurology, Institute of Neurology, London, UK., Sweeney MG, Brockington M, Lennox GG, Lawton NF, Kennedy CR, Morgan-Hughes JA, Harding AE |
| Jazyk: | angličtina |
| Zdroj: | Brain : a journal of neurology [Brain] 1993 Jun; Vol. 116 ( Pt 3), pp. 617-32. |
| DOI: | 10.1093/brain/116.3.617 |
| Abstrakt: | The mitochondrial DNA (mtDNA) transfer RNA (tRNA)Lys A-->G(8344) mutation was identified in seven patients. These patients and their relatives were assessed clinically; in one family the mutation was deduced to be present in four generations. The phenotype in index cases was consistent with the syndrome of myoclonic epilepsy with ragged red fibres, with the core clinical features of myoclonus, ataxia and seizures. Amongst other features, progressive external ophthalmoplegia, Leigh's syndrome and stroke-like episodes were observed, well recognized in mitochondrial myopathies but novel manifestations of this genotype. Samples of blood and muscle were analysed for the proportion of mutant mtDNA using an oligonucleotide hybridization technique. The proportion of mutant mtDNA in blood was significantly greater in symptomatic than asymptomatic cases. Furthermore, the proportion of mutant mtDNA in blood correlated with age of onset of disease and clinical severity assessed by a simple scale. Study of disease associated with the tRNA(Lys) A-->G(8344) mutation provides further insight into the pathogenesis and transmission of mitochondrial diseases. Quantification of the proportion of mtDNA in tissues demonstrates that this is a major factor determining the course of disease, but other, as yet unidentified factors are also likely to play a role. |
| Databáze: | MEDLINE |
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