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Query: UMLS:C0162671 (MELAS)
 587 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Instabilities and point mutations of the high molecular weight mitochondrial DNA (mtDNA) were shown to be correlated with various degenerative processes in both lower eukaryotes as well as in mammals. In filamentous fungi, circular and linear plasmids were demonstrated to be involved in mtDNA rearrangements and in the genetic control of senescence. In addition, in these eukaryotic microorganisms, which have proved to be ideal model systems in experimental gerontology, a number of nuclear genes were identified controlling the stability of the mitochondrial genome. Although the mitochondrial genome of mammals, including humans, appears to be quite stable in comparison to other species, mtDNA instabilities of the type described in fungi were observed in mitochondria of patients with different mitochondrial degenerative disorders (CPEO, KSS, Pearson syndrome, LHON, MERRF, MELAS). It was later demonstrated that such mtDNA rearrangements appear to accumulate progressively during aging in human subjects. These data suggest that instabilities of the mitochondrial genome may play an important role in the control of life span not only in lower eukaryotes, but also in humans.
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PMID:The role of mitochondrial DNA rearrangements in aging and human diseases. 848 27

Mitochondrial DNA is a unique, maternally inherited molecule encoding several subunits of the respiratory enzyme chain. In several mitochondrial cytopathies mutations have been described in this genome viz. large-scale heteroplasmic deletions in syndromes with progressive external ophthalmoplegia and point mutations in MELAS and MERRF encephalomyopathies. We here report Southern blot analyses in the cases of CPEO we have seen and describe the search for point mutations in MELAS and MERRF. Mitochondrial genetic sequencing in normal and disease controls as well as in patients has confirmed the pathogenic nature of a tRNA Lys point mutation in MERRF. We propose a novel mitochondrial structural gene mutation in a MELAS--like encephalomyopathy: an A-->G substitution at position 11084 leading to a Thr to Ala replacement in the ND4 subunit of complex I.
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PMID:The molecular genetics of mitochondrial cytopathies: the Melbourne experience. 134 60

Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products.
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PMID:Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. 175 69

During a 4-year period 1984 to 1988, 20 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were found to have a mitochondrial disease. Each diagnosis was based on the results of thorough biochemical and morphologic investigations. The patients were separated into one series with mainly encephalopathy (n = 14) and another with mainly myopathy (n = 6). The patients with encephalopathy had the following syndromes: Kearns-Sayre (n = 2), MERRF (myoclonus epilepsy and ragged red fibers; n = 2), MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes; n = 3), Alpers (n = 3), Leigh (n = 1), and other variants (n = 3). In patients with myopathy, three had hypertrophic nonobstructive cardiomyopathy. Ultrastructural abnormalities of mitochondria were the most common morphologic changes in the muscle biopsies. Complex I deficiency was most common in the patients with encephalopathy. All of the patients with myopathy had complex IV deficiency. Mutations of mitochondrial DNA were found in six patients with encephalopathy. We conclude that identification of defects at the DNA level and determination of the phenotypic expression with clinical, morphologic, and biochemical methods are fundamental for future rational classification of mitochondrial disorders.
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PMID:Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. 186 Dec 10

EEG was studied in 25 children and adolescents with mitochondrial encephalomyopathies, defined on the basis of clinical, biochemical and morphological criteria. Twenty cases conformed to well-known mitochondrial syndromes: Alpers syndrome [6], Leigh syndrome [2], MERRF (myoclonus epilepsy and ragged red fibers) syndrome [3], MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) syndrome [5] and Kearns-Sayre syndrome [4]. Many patients were followed for several years with repeated EEG. In all, 112 EEG records were included in the study. A common feature of all the mitochondrial encephalomyopathic syndromes was slowing of the alpha rhythm. Epileptic discharges were seen in most syndromes. In spite of the small number of cases in each group, in Alpers, MERRF and MELAS syndromes we found sequential EEG patterns which seemed to be typical of the respective syndromes. In contrast, in Kearns-Sayre syndrome, a slow background rhythm was the only consistent finding. We conclude that EEG, especially repeated recordings, may be of help in the diagnostic evaluation of mitochondrial encephalomyopathies.
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PMID:EEG findings in children and adolescents with mitochondrial encephalomyopathies: a study of 25 cases. 192 9

Biochemical results concerning 64 patients suspected of mitochondrial myopathies are presented. Four clinical groups were studied including 21 encephalomyopathies, 42 ocular myopathies, 8 isolated myopathies and 3 cardiomyopathies. In 26 cases, the coexistence of a normal mitochondrial DNA and a mutated mitochondrial DNA (heteroplasmy) was found (19 simple deletions, 4 multiple deletions and 3 punctual mutations) and all cases presented with ocular disorders (excepted 2 cases with MERRF). Furthermore, 1 complex I deficiency (1 ocular myopathy), 1 complex IV deficiency (1 adult encephalomyopathy type Leigh), 3 complexes I + IV deficiencies (2 cases with a cardiomyopathy and 1 familial MELAS) and 2 pyruvate (1 adult from of Leigh's encephalomyopathy) dehydrogenase deficiencies (clinically and genetically different) did not show evidence of mitochondrial DNA mutation.
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PMID:[Mitochondrial function and mitochondrial DNA in a series of 64 patients suspected of having mitochondrial myopathy]. 196 51

Among 40 patients with ragged red fibers in muscle biopsy, all but two met criteria for one of the recognized mitochondrial myopathies: Kearns-Sayre syndrome (6 patients); other ophthalmoplegias (17): MELAS (3); MERRF (2); limb myopathy (5); and exercise intolerance (3). Two patients had MNGIE (mitochondrial myopathy with neuropathy, gastrointestinal symptoms and encephalopathy) and one had spinal muscular atrophy. The myopathy had features of facioscapulohumeral dystrophy in 4 patients. This analysis provides 4 lines of evidence to reinforce the view that, despite occasional "overlap" cases, distinct syndromes can be recognized. First, there are clinical differences. Second, KSS is almost never familial but MELAS and MERRF are often familial. Third, in this series, as in others, all deletions of mtDNA were found in patients with either KSS or non-familial PEO. With a possible single exception, none of the familial cases had KSS and no familial cases included a deletion of mtDNA. Others have found evidence of mtDNA point mutations in MERRF, and maternal inheritance suggests that point mutations will be found in MELAS. Finally, postmortem findings differ in KSS, MELAS, and MERRF. For all of these reasons, we believe it is useful to separate cases on clinical grounds. Deletions and point mutations of mtDNA are becoming defining characteristics of these syndromes.
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PMID:Clinical syndromes associated with ragged red fibers. 196 52

Two 30-year old twins, one male, the other female, were followed up for 20 years for predominantly proximal muscular deficit without increase of muscle enzymes. The lactic acid level was elevated at rest and further increased during exercise. Muscle biopsy revealed mitochondrial abnormalities. Encephalopathy was also present. The female patient had been treated, at the age of 10 years, for myoclonic attacks which regressed when she was over 18 years. None of the two patients had dementia. CT and MRI showed very extensive and symmetrical lesions of the white matter which did not involve the basal ganglia. These two cases are interesting on three scores: (1) clinically, the woman exhibited symptoms of the MELAS syndrome (without cerebral vascular accidents) and symptoms of the MERRF syndrome, which suggests the existence of borderline cases; (2) genetically, our cases were in favour of a so-called "maternal" heredity (boys are affected in all cases): here both sexes were involved but the phenotype varied; (3) biochemically, we found no enzyme activity deficit likely to explain the clinical features. The significance of a selective increase of cytochrome c oxidase in both mother and daughter is unclear.
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PMID:[Mitochondrial myopathy and leukoencephalopathy in twins of different sexes]. 196 56

According to present knowledge, mutations of mitochondrial DNA (mtDNA), implicated in the mitochondrial theory of carcinogenesis that had been inaugurated 50 years ago by Graffi, appear to be involved in malignant transformation of cells, although no definite evidence has been provided, as yet. However, as very recently elucidated, a clear-cut association exists between different classes of mutations of mtDNA (among them point mutations, deletions and duplications) and some human mitochondriopathies, particularly neuromuscular diseases. These include Leber's hereditary optic neuropathy, the Kearns-Sayre syndrome and two encephalomyopathies known by the acronyms MERRF and MELAS syndrome. The different alterations of mtDNA, though variable, can be assigned to defined positions on the genetic map of mtDNA. Point mutations of mtDNA seem to occur preferentially in conjunction with maternally inherited disorders. Although the results obtained so far are of interest mainly in terms of cognitive theory they provide new stimuli for the development of molecular diagnosis, genetic counselling and possibly for more effective treatment of the above diseases.
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PMID:[Mutations of mitochondrial DNA and their relation to neuromuscular diseases]. 220 92

Autoantibodies present in the autoimmune disease primary biliary cirrhosis react by immunoblotting with four human skeletal muscle mitochondrial antigens of 70 kDa, 52 kDa, 50 kDa and 45 kDa, identified as the lipoate acetyl transferases (E2) of the pyruvate dehydrogenase, component X of E2 pyruvate dehydrogenase, E2 of 2-oxo glutarate dehydrogenase and E2 of branched-chain 2-oxo acid dehydrogenase complexes respectively. These autoantibodies have been employed as a novel probe to study whether there is a defect in the synthesis of the 2-oxo acid dehydrogenase complexes in patients with mitochondrial respiratory chain disorders. The reactive antigens are present normally in four patients with oculomyopathy in whom partial deletions of the mtDNA have been detected, and in two patients with MERRF and MELAS encephalomyopathy. Thus, unlike in the yeast Saccharomyces cerevisiae, there appear to be no regulatory interactions which coordinate the assembly of the mitochondrial respiratory chain with the development of the pyruvate dehydrogenase complex, which plays an important role in regulating the flow of metabolic intermediates to oxidative energy metabolism.
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PMID:Antimitochondrial autoantibodies of primary biliary cirrhosis as a novel probe in the study of 2-oxo acid dehydrogenases in patients with mitochondrial myopathies. 224 28


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