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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we comparatively analysed deltoid histochemistry, biochemistry and mitochondrial DNA (mtDNA) in two groups of ten sporadic ocular mitochondrial myopathies (OMM), respectively with and without ragged red fibres (RRF). (1) All but one RRF--patients presented the mild form of OMM with blepharoptosis but without ophthalmoplegia; (2) the occurrence of cytochrome c oxidase deficient (COX-) fibres was significantly higher in the RRF+ group, but four RRF- cases also showed COX- fibres; (3) no difference was observed in biochemical findings between the groups; (4) two RRF- patients without COX- fibres showed mtDNA heteroplasmy; (5) in two RRF- patients without deltoid mtDNA deletion, biopsy of an eyelid muscle showed significant mitochondrial alterations. These results suggest that the expression of a mitochondrial defect can vary and that the absence of RRF in a skeletal muscle biopsy does not necessarily rule out the diagnosis of OMM, if other data support that.
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PMID:Variability of the expression of muscle mitochondrial damage in ocular mitochondrial myopathy. 130 Jan 88

Defects of the mitochondrial respiratory chain form a clinically and biochemically heterogeneous group of diseases. Mitochondrial diseases include myopathies and multisystem disorders that are defined either by biochemical abnormalities of the mitochondria or by the presence of "ragged red fibers" in muscle-biopsy specimens stained with modified Gomori's trichrome stain. Several syndromes have been identified. Typical Kearns-Sayre syndrome is a sporadic condition that is characterized by an onset before the age of 20, progressive external ophthalmoplegia, pigmentary retinopathy and cardiac disorders. Mitochondrial DNA deletions were found in patient with Kearns-Sayre syndrome. We report the case of a 33 year-old woman, with neuromuscular syndrome of the Kearns-Sayre type, insulin-sensitive diabetes and complete heart block, who was implanted a pacemaker.
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PMID:[Mitochondrial disease and complete heart block. Kearns-Sayre syndrome. Description of a case]. 130 Apr 76

In an attempt to elucidate the pathogenesis of focal cytochrome c-oxidase (COX) deficiency in skeletal muscle from patients with chronic progressive external ophthalmoplegia (CPEO), we examined the longitudinal distribution of COX activity in single muscle fibers from 6 CPEO patients with muscle mitochondrial DNA (mtDNA) deletions. A new method for teasing single muscle fibers, recently developed in our laboratory, revealed fibers with COX-positive and -negative segments in all 6 patients. The borders between the enzyme-positive and -negative segments in these fibers were sharply delineated, so that the length of each COX-negative segments could be accurately measured. The proportion of the sum of the lengths of the enzyme-negative segments to the total length of the muscle fibers correlated well with the proportion of deleted mtDNA, suggesting that abnormal mitochondria harboring mutant mtDNA may be responsible for the focal loss of COX activity.
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PMID:Segmental cytochrome c-oxidase deficiency in CPEO: teased muscle fiber analysis. 131 76

In the past few years several syndromes have been associated with lesions of the human mitochondrial DNA. MtDNA is a small, circular extra-nuclear chromosome encoding essential components of the respiratory chain. MtDNA-related syndromes can be divided into two groups: mitochondrial encephalomyopathies, characterized by the presence of ragged-red fibres (RRF) as the morphological hallmark, or "pure" encephalopathies with no gross morphological abnormalities in muscle. The first group includes myoclonic epilepsy with ragged-red fibres (MERRF), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO) and a new entity, maternally inherited myopathy and cardiomyopathy. The second group includes Leber's Hereditary Optic Neuroretinopathy (LHON) and the newly described ataxia-retinitis pigmentosa-dementia complex. Three kinds of molecular lesions have been identified: point mutations of protein encoding mtDNA-genes (similar to yeast mit- mutations); point mutations of mtDNA-tRNA genes (similar to yeast syn- mutations); and large-scale rearrangements of mtDNA (similar to yeast rho- mutations). In general, "mit-" mutations are responsible for non-RRF encephalopathies, while "syn-" and "rho-" mutations are associated with mitochondrial encephalomyopathies with RRF. Furthermore, point mutations (mit- and syn-) are usually maternally- inherited, while large-scale mtDNA rearrangements are either sporadic or inherited as mendelian traits. In most cases, the molecular detection of the known defects of mtDNA can be carried out by non-invasive techniques, thus making it an easy and relatively inexpensive procedure in the differential diagnosis of the mitochondrial disorders, a rapidly expanding area of clinical neurology.
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PMID:Defects of mitochondrial DNA. 134 53

Multiple deletions of mitochondrial DNA (mtDNA) have recently been described in a number of patients with neurological disorders. Most cases have been clinically characterized by autosomal dominant inheritance, adult onset, and a slowly progressive course with external ophthalmoplegia and muscle weakness. Some patients have had evidence of central or peripheral nervous system involvement or episodes of myoglobinuria. Muscle biopsy findings include ragged-red fibres (RRF), muscle fibres with absent COX-activity and abundant abnormal mitochondria with paracrystalline inclusions. Biochemically, a generalized reduction in the activities of mtDNA-encoded enzymes is observed in skeletal muscle. Southern blotting or PCR analysis reveal multiple populations of deleted mtDNA. The deletions occur at multiple sites between the replication initiation sites, involving a large portion of mtDNA, and most deletions seem to be flanked by direct sequence repeats, shown to be "hot spots" in the case of single large deletions. Apparently, a defect in a nuclear gene results in multiple deletions of mtDNA. Both clinical, genetic and molecular genetic observations indicate heterogeneity of this new disease category, apparently based on a disturbance in the "cross-talk" between the nuclear and the mitochondrial genomes.
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PMID:Disorders associated with multiple deletions of mitochondrial DNA. 134 54

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

With the discovery of mitochondrial DNA (mtDNA) mutations in different neuromuscular disorders, investigations now seek to clarify how the mutant mtDNA induces biochemical and morphologic defects. In one of the most important approaches human mutant mtDNA is transferred into cells that lack mtDNA to examine the relationship between the amount of mutant mtDNA and defects in cell growth, respiration and enzyme activities. The resulting cells are 'cybrids'; these clonal cells contain the heteroplasmic mutant and normal mtDNA from patients with mitochondrial diseases. The mitochondria become functionally defective when the amount of mutant mtDNA exceeds a certain threshold, which differs from mutation to mutation: 60 to 70% in chronic progressive external ophthalmoplegia (CPEO) and probably 95% in the syndromes of mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes (MELAS), and myoclonic epilepsy with ragged red fibers (MERRF). This threshold effect may explain the tissue-specific patterns of clinical expression.
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PMID:Mitochondrial diseases. 139 36

Myoclonus epilepsy with ragged-red fibers (MERRF) has been shown to be associated with a specific point mutation at the nucleotide 8344 in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). We screened 6 patients with clinically diagnosed MERRF and 1 patient with ocular myopathy for point mutations in the tRNA(Lys) gene, using single strand conformation polymorphism (SSCP) analysis, which can detect even a 1-basepair difference between 2 DNA sequences. Using SSCP and consequent DNA sequencing, we identified the known MERRF mutation in 4 out of 6 MERRF patients, as well as in 1 patient with a new clinical phenotype associated with this mutation: progressive external ophthalmoplegia, muscle weakness and a lipoma, but no myoclonus or epilepsy. Two of the patients with clinical MERRF had neither the MERRF-mutation nor any other mutations in the tRNA(Lys) gene. Using SSCP analysis, we also detected a new polymorphism in 1 patient. Thus, SSCP analysis can be applied to search effectively and rapidly for point mutations or polymorphisms in mitochondrial DNA.
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PMID:Use of single strand conformation polymorphism analysis to detect point mutations in human mitochondrial DNA. 143 90

Two sisters in the first year of life presented with a proximal tubulopathy of unknown etiology. They subsequently developed a pluritissular disorder including diabetes mellitus, skin abnormalities, mitochondrial myopathy with ragged-red fibers, and cerebellar ataxia. Their mother had ptosis, ophthalmoplegia, and muscle weakness. Analysis of the mitochondrial respiratory chain showed a complex III deficiency in both skeletal muscle and lymphocytes of the second girl. Southern blot analysis provided evidence for a heteroplasmic partial duplication of the mtDNA (26 kb), involving one full-length and one partly deleted mitochondrial genome and with one single abnormal junction between the genes for ATPase 6 and cytochrome b. Using PCR amplification of lymphocyte DNA, we were able to detect minute amounts of duplicated molecules in the mother, which provided evidence for maternal inheritance of the partial duplication. While maternal transmission of point mutations have been reported in Leber disease, retinitis pigmentosa, and MERRF disease, this observation is, to our knowledge, the first example of a maternally inherited duplication of the mitochondrial genome in man.
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PMID:Maternally inherited duplication of the mitochondrial genome in a syndrome of proximal tubulopathy, diabetes mellitus, and cerebellar ataxia. 153 Nov 67

Among various mitochondrial encephalomyopathies, there are three distinct clinical entities, including chronic progressive external ophthalmoplegia (CPEO), myoclonus epilepsy associated with ragged-red fibers (MERRF), and mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS). They are now clearly demonstrated to have the respective specific mitochondrial (mt) DNA mutations, which facilitate us to analyse mtDNA for practical diagnosis. With molecular analysis on 40 CPEO, 6 MERRF and 40 MELAS patients, most patients in the individual disorders had the disease-specific mutations. In CPEO, 31 of 40 patients had deleted mtDNA in a heteroplasmic distribution; the mutant mtDNA were present in a large amount in the skeletal muscle and other symptomatically affected organs as observed on Southern blotting and polymerase chain reaction (PCR). In MERRF (6 out of 6 patients) and MELAS (32 out of 40 patients), mutant mtDNA was easily detectable with PCR not only in skeletal muscle but also in blood cells from several patients examined. The results lead us to conclude that molecular analysis helps to obtain definite diagnosis of the diseases without loss of time.
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PMID:[Clinical application of molecular diagnosis for mitochondrial encephalomyopathies]. 155 59


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