Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 22 subjects carrying the A3243G point mutation of human mitochondrial DNA (mtDNA). In 14 cases the clinical phenotype was characterized by mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), while 8 patients had chronic progressive external ophthalmoplegia (CPEO). The proportion of A3243G heteroplasmy in muscle was determined by two methods; densitometry on a diagnostic restriction-fragment length polymorphism and solid-phase mini-sequencing. We found a highly significant inverse correlation between the percentage of A3243G mutation and the specific activity of complex I, the respiratory complex with the highest number of mtDNA-encoded subunits, suggesting a direct effect of the mutation on mtDNA translation. No correlation was observed between the percentage of mutated mtDNA and the presence or absence of specific clinical features, such as stroke, ophthalmoplegia and diabetes mellitus. However, in the MELAS group the percentage of mutated mtDNA molecules was strongly correlated with the age of onset, while no such correlation was found in the CPEO group, suggesting a different time-dependent evolution of the mutation in the two groups. Finally, in contrast with other mtDNA mutations associated with ragged-red fibres (RRF), in both MELAS3243 and CPEO3243 we observed a high proportion of RRF that were positive to the histochemical reaction to cytochrome c oxidase, a morphological feature that seems to be specific for the neuromuscular phenotypes associated with mutations affecting the tRNA(Leu(UUR)) gene.
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PMID:Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNA. 764 39

We present a case of Kearns-Sayre syndrome diagnosed in a boy with retinitis pigmentosa ophthalmoplegia, ancephalomyopathy and cardiomyopathy. A single large-scale mtDNA deletion at very low level in the blood sample using Southern blot analyses and multiprimer DNA amplification was detected. This case demonstrates that retinitis pigmentosa may be due to genetic mitochondrial disturbances.
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PMID:[Retinitis pigmentosa in Kearns-Sayre syndrome resulting from mutation of mitochondrial DNA "de novo"]. 764 65

Using in situ hybridization, we studied muscle biopsy specimens from 4 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Three of the 4 patients with MELAS had a mutation at position 3243 of mitochondrial DNA (mtDNA) in the transfer RNALeu(UUR) gene, and the other patient had a mutation at position 3271 in the same transfer RNALeu(UUR) gene. Quantitative analysis using Southern blot hybridization and polymerase chain reaction showed 80 to 90% mutant mtDNA in muscle. In situ hybridization analysis showed that total mtDNAs (both normal and mutant) were extremely increased in blood vessels with high succinate dehydrogenase activity (strongly succinate dehydrogenase-reactive blood vessels) and ragged-red fibers. Cytochrome c oxidase activity in most of these reactive blood vessels and ragged-red fibers was positive. The similar morphological behavior in these vessels and fibers suggests that an increase in mutant mtDNA is responsible for mitochondrial proliferation and dysfunction in both tissues where cytochrome c oxidase is not a primarily defective enzyme. The pattern of expression of genes for mtDNA-encoded ribosomal RNA and the protein-coding region cytochrome c oxidase subunit II were similar in muscle specimens of patients with MELAS, patients with chronic progressive external ophthalmoplegia, and normal control subjects, and also between the two MELAS mutations. These results do not support the hypothesis that impaired transcription termination is a molecular defect in MELAS.
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PMID:Increased mitochondrial DNA in blood vessels and ragged-red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). 768 81

The molecular mechanisms by which the nuclear genome regulates the biosynthesis of mitochondrial DNA (mtDNA) are only beginning to be unravelled. A naturally occurring in vivo model for a defect in this cross-talk of two physically separate genomes is a human disease, an autosomal dominant progressive external ophthalmoplegia, in which multiple deletions of mtDNA accumulate in the patients' tissues. The assignment of this disease locus to 10q 23.3-24.3 is the first direct evidence for involvement of both nuclear and mitochondrial genomes in a single disorder.
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PMID:An autosomal locus predisposing to deletions of mitochondrial DNA. 771 41

The mode of inheritance of Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) have not yet been established, since most cases are sporadic. We studied skeletal muscle pathology and mitochondrial DNA (mtDNA) in a sporadic KSS patient (proband) and examined mitochondrial function of the muscle in his asymptomatic family members. The proband was a 56-year-old male with bilateral ptosis, external ophthalmoplegia, retinal degeneration and cardiac conduction disturbance. Biopsied deltoid muscle showed 9.7% of ragged red fibers without cytochrome oxidase (COX) activity and abnormal mitochondria on electron microscopy. Analysis of muscle mtDNA revealed a 4,977 bp deletion between nt. 8,483 and 13,459. None of the family members had symptoms similar to those of the proband. However, an aerobic exercise test of 15W for 15 minutes with an ergometer induced a marked increase in serum lactate levels in the proband's mother. Histology of her biopsied deltoid muscle showed 0.3% of ragged red fibers without COX activity and morphologically abnormal mitochondria. These findings indicate that the abnormal mitochondria of the proband were transmitted from his asymptomatic mother. This also suggests that some of the sporadic KSS/CPEO cases are inherited one.
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PMID:[A case of Kearns-Sayre syndrome whose asymptomatic mother had abnormal mitochondria in skeletal muscle]. 778 Dec 38

The investigation of pathogenic mitochondrial DNA (mtDNA) mutations has revealed a complex relation between patient genotype and phenotype. For unknown reasons, some mtDNA mutations produce specific clinical manifestations such as chronic progressive external ophthalmoplegia; myoclonic epilepsy and ragged-red fiber disease (MERRF); and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). To enhance our understanding of the association between genotype and phenotype, we investigated a patient with mitochondrial encephalomyopathy and severe cerebral calcifications for a mtDNA mutation. There was a deletion of one of three T:A nucleotide pairs in the tRNALeu(UUR) gene of the mtDNA involving positions 3271 to 3273. Pedigree analysis suggested that this mutation may have occurred spontaneously in the proband. This analysis represents the smallest mtDNA deletion observed to date and is the first deletion identified within a mitochondrial tRNA. This observation emphasizes the importance of delineating the precise mutation responsible for an oxidative phosphorylation disease for patient diagnosis as well as for genetic counseling of maternal lineage relatives.
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PMID:Mitochondrial encephalomyopathy associated with a single nucleotide pair deletion in the mitochondrial tRNALeu(UUR) gene. 785 27

The phenotypes of Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) are closely associated with deletions of mitochondrial DNA (mtDNA). Recent evidence suggesting that more than one type of rearrangement may be present in KSS led us to reinvestigate 18 patients with KSS or CPEO for the presence of mtDNA rearrangements other than deletion. mtDNA duplication was detectable in 10 of 10 patients with KSS, while deletion monomers were the only recombinant mtDNA easily detectable in eight of eight patients with CPEO. Deletion dimers were found only in cases having duplications. Thus, duplications of mtDNA seem to be a hallmark of KSS, including a patient where Pearson's syndrome was the first manifestation. We suggest that duplication of mtDNA is characteristic of the early-onset disease KSS, and that the balance of mtDNA rearrangements may be central to the pathogenesis of this unique group of disorders.
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PMID:Are duplications of mitochondrial DNA characteristic of Kearns-Sayre syndrome? 795 Dec 43

We report extensive deletion of muscle mitochondrial DNA and ophthalmological findings in a patient with progressive external ophthalmoplegia. The patient was a twenty-nine-year-old female who had suffered from slowly progressive external ophthalmoplegia for ten years. No abnormal finding was observed in the funduscopic examination, but fluorescein angiography showed mottled hyperfluorescence. The final rod threshold for the dark adaptation testing was slightly elevated. The flash electroretinogram showed a slightly attenuated b wave. Ragged-red fibers were observed in muscle biopsies. A biochemical and histochemical study showed that cytochrome c oxydase activity was reduced. The length of deletion of the mitochondrial DNA, determined by polymerase chain reaction, was 4977 base pairs, flanked by a 13-base pair direct repeat.
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PMID:[Progressive external ophthalmoplegia with extensive mitochondrial DNA deletion]. 797 25

We report a patient with mitochondrial encephalomyopathy presenting parkinsonism, as well as her brother who had ataxia but not parkinsonism. Both patients had myopathy, deafness, and insulin-dependent diabetes mellitus. The proband was a 55-year-old woman, who has developed progressive difficulty in walking and slowness of movement since 53 years of age, becoming bed-ridden at 55. Neurological examination revealed mental impairment, a masked face, Myerson's sign, vertical supranuclear ophthalmoplegia, and severe sensorineural deafness, hypokinesia, rigidospasticity, and weakness of the extremities. But tremor and cerebellar ataxia were absent. Her 48-year-old brother gradually developed weakness of the lower extremities and drunken gait over a few years. On neurologic examination, vertical supranuclear ophthalmoplegia, moderate sensorineural deafness, and cerebellar ataxia were present, but parkinsonism was absent. Three other siblings were reported to have died in early childhood. Cranial MR imaging showed cerebral atrophy and mild atrophy of the cerebellar vermis as well as mild periventricular hyperintensities in T2-weighted images in both patients. However, no infarcts were seen. Laboratory investigations revealed slightly elevated lactate and pyruvate levels in the proband and elevation of pyruvate in her brother. A biopsy specimen obtained from the quadriceps muscle showed ragged-red fibers with modified Gomori trichrome staining, and a decrease of complex I+III and complex II+III activity in the proband. Mitochondrial DNA (mtDNA) analysis using the polymerase chain reaction and restriction enzyme Apa I showed a point mutation in the tRNA(Leu)(UUR)) gene (an A to G transition at nucleotide 3243) in both patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mitochondrial encephalomyopathy associated with parkinsonism and a point mutation in the mitochondrial tRNA(Leu)(UUR)) gene]. 802 31

A 17-year-old girl was admitted to our hospital because of drowsiness, diplopia and gait difficulty. She had been well until ten days before admission when fever, drowsiness, headache and general fatigue developed. On admission, there were drowsiness, ophthalmoplegia, ataxia and hyporeflexia. CSF cells and anti-CMV antibody titers increased. CMV-DNA was detected in the CSF by the polymerase chain reaction (PCR). Serum anti-GQ1b antibody was positive. During recovery, forced laughing temporarily appeared. The neurological symptoms disappeared completely. CSF anti-CMV antibody titers became normalized and CSF CMV-DNA-PCR became negative. This is the first case report of Bickerstaff's brainstem encephalitis associated with CMV infection.
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PMID:[Bickerstaff's brainstem encephalitis associated with cytomegalovirus infection]. 802 40


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