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 report a patient with mitochondrial diabetes mellitus associated with the A3243G mutation (MDM3243). The patient is a 77-year man with diabetes. At age 68, he noticed diplopia, due to superior rectus muscle palsy of the right eye. At age 70, he noticed lipoma on the right arm. The pathology of his muscle revealed some ragged-red fibers, and focal cytochrome c oxidase deficiency. Hence, he may have a pathogenetic mechanism in common with CPEO (chronic progressive external ophthalmoplegia) or mitochondria-related autoimmune disorder associated with mononeuropathy. He had the rate of 0.102% for heteroplasmy of 3243 mitochondrial DNA mutation in leukocytes. This case's heteroplasmy level is the smallest among the reported cases of MDM3243 in the literature. 3243 mitochondrial DNA mutation is known to induce a lack of uridine-modification in tRNA(Leu(UUR)) at the first letter of the anticodon, with which the third letter of the codon pairs, and decline of the pairing of the anticodon of tRNA with the codon of mRNA, suggesting the termination of polypeptide-elongation to generate premature proteins. Therefore, we speculate that these premature proteins may accumulate overtime, thereby affecting cells in target organs.
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PMID:Lipoma and opthalmoplegia in mitochondrial diabetes associated with small heteroplasmy level of 3243 tRNA(Leu(UUR)) mutation. 1475 94

We have sequenced all mitochondrial tRNA genes from a patient with chronic progressive external ophthalmoplegia (CPEO) and mitochondrial myopathy, who had no detectable large mtDNA deletions. Direct sequencing failed to detect previously reported mutations and showed a heteroplasmic mutation at nucleotide 12,276 in the tRNA(Leu(CUN)) gene, in the dihydrouridine stem, which is highly conserved through the species during evolution. RFLP analyses confirmed that 18% of muscle mtDNA harbored the mutation, while it was absent from DNA of fibroblasts and lymphocytes of the proband and in 110 patients with other encephalomyopathies. To date, besides large and single nucleotide deletions, several point mutations on mitochondrial tRNA genes have been reported in CPEO patients, but only three were in the gene coding for tRNA(Leu(CUN)).
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PMID:A novel heteroplasmic tRNA(Leu(CUN)) mtDNA point mutation associated with chronic progressive external ophthalmoplegia. 1564

In the present study we assessed the prevalence and nature of hearing loss in patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) due to single large-scale mitochondrial DNA (mtDNA) deletion or mtDNA tRNA (Leu (UUR)) A3243G point mutation (A3243G PM). 14 patients with mtDNA deletion and three patients with A3243G PM underwent audiological evaluation comprising pure-tone and speech audiometry as well as transient evoked otoacoustic emissions (OAE). Audiological evaluation revealed hearing impairment in 10/17 patients. Hearing loss was mild to moderate predominantly affecting high frequencies in five patients with subjective hearing problems (three patients with mtDNA deletions, two patients with A3243G PM). Subclinical hearing deficits restricted to high frequencies were seen in further five asymptomatic patients (four patients with mtDNA deletions, one patients with A3243G PM). Audiological findings suggested a cochlear origin of hearing loss in all subjects. Our results demonstrate that CPEO or KSS patients due to mtDNA deletion or A3243G PM are at high risk of developing sensorineural hearing deficits.
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PMID:Sensorineural hearing loss in patients with chronic progressive external ophthalmoplegia or Kearns-Sayre syndrome. 1582 67

We sequenced all genes of mitochondrial tRNAs of a patient with chronic progressive external ophthalmoplegia with 5% ragged red fibres and 15% COX-negative fibres but without macrorearrangements of mitochondrial DNA (mtDNA). Direct sequencing showed a novel heteroplasmic G>A substitution in position 12316 of tRNA(Leu(CUN)) gene. This change destroys a highly conserved G-C base coupling in tRNA TpsiC branch. By RFLP analysis we could demonstrate different degrees of heteroplasmy in different patient's tissues. This alteration, absent in a population of 110 patients with different encephalomyopathies, can be considered pathogenic: it is the tenth tRNA(Leu(CUN)) pathogenic mutation described up to date.
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PMID:Chronic progressive external ophthalmoplegia: a new heteroplasmic tRNA(Leu(CUN)) mutation of mitochondrial DNA. 1860 65

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome are caused mainly by the A3243G mutation of the mitochondrial genome. The A3243G substitution of mitochondrial DNA (mtDNA) is also responsible for various, other clinical phenotypes and syndromes. Here we report the case of a 33-year-old woman, with childhood onset ophthalmoplegia externa, progressive, generalised exercise intolerability, muscle weakness, hypacusis and diabetes mellitus as the symptoms of mitochondrial disease. Genetic analysis of the mitochondrial DNA revealed a heteroplasmic A to G substitution at position 3243 in the tRNS Leu(UUR) gene. In our case the classical MELAS phenotype has not yet appeared, however, some examples show in the literature that maternally inherited diabetes mellitus, progressive hypacusis, progressive ophthalmoplegia externa, exercise intolerance, and myopathy are often linked to as isolated symptoms of A3243G mutation. The phenotype in the family is consistent, the proband's daughter has ptosis, exercise intolerance, and myopathy, too. A brief summary of the different clinical phenotypes associated with A3243G mutation, and of the different mtDNA mutations which can cause chronic progressive ophthalmoplegia externa (CPEO) will also be reviewed in this case report.
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PMID:[Maternally inherited diabetes mellitus, deafness, chronic progressive external ophthalmoplegia and myopathy as the result of A3243G mutation of mtDNA]. 1870 13

We sequenced all mitochondrial tRNA genes in a 61-year-old man with chronic progressive external ophthalmoplegia and mitochondrial myopathy but without mtDNA rearrangements, and identified a heteroplasmic m.3244G>A mutation in the tRNA(Leu(UUR)) gene. This mutation had been previously associated with the MELAS phenotype, but not described in any detail. The mutation load in muscle was 84% and COX-negative fibers harbored greater levels of mutant genomes than COX-positive fibers. The m.3244G>A mutation affects a highly conserved nucleotide in the dihydrouridine loop and has been associated with a wobble modification deficiency of the mutant tRNA.
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PMID:The m.3244G>A mutation in mtDNA is another cause of progressive external ophthalmoplegia. 1928 65

Pathogenic mutations in the tRNA(Leu(UCN)) gene of mitochondrial DNA (mtDNA) have been invariably accompanied by skeletal myopathy with or without chronic progressive external ophthalmoplegia (CPEO). We report a young woman with a heteroplasmic m.12276G>A mutation in tRNA(Leu(UCN)), who had childhood-onset and slowly progressive encephalopathy with ataxia, cognitive impairment, and hearing loss. Sequencing of the 22 tRNA mitochondrial genes is indicated in all unusual neurological syndromes, even in the absence of maternal inheritance.
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PMID:Slowly progressive encephalopathy with hearing loss due to a mutation in the mtDNA tRNA(Leu(CUN)) gene. 2002 7

We describe a 62-year-old woman with chronic progressive external ophthalmoplegia (CPEO), multiple lipomas, diabetes mellitus, and a novel mitochondrial DNA (mtDNA) mutation at nucleotide 4302 (4302A>G) of the tRNA(Ile) gene (MTTI). This is the first mutation at position 44 in the variable loop (V loop) of any mitochondrial tRNA. The muscle biopsy revealed 10% ragged-red/ragged-blue fibers and 25% cytochrome c oxidase (COX)-deficient fibers. No deletions or duplications were detected by Southern blot analysis. The 4302A>G transition was present only in the patient's muscle and single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient than in normal fibers. Like tRNA(Leu(UUR)), tRNA(Ile) appears to be a "hot spot" for mtDNA mutations causing CPEO.
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PMID:A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO). 2014 59

Mitochondrial disorders are often associated with mutations in mitochondrial tRNA. Independent observation of the same molecular defect in unrelated subjects is a generally required proof of pathogenicity. A sporadic case of chronic external ophthalmoplegia (cPEO) with ragged red fibres (RRFs) has been previously related to an m.12316G>A substitution in tRNA(Leu(CUN)). Sequencing muscle-derived mtDNA, we found the m.12316G>A substitution in an adult woman with mitochondrial myopathy and respiratory impairment. Her muscle biopsy presented several cytochrome c oxidase-negative (COX-) fibres, and RRFs as signs of mitochondrial proliferation. Restriction-fragment length polymorphism (RFLP) analysis of the mutation in isolated muscle fibres showed a threshold of at least 60% of mutated mtDNA to determine a COX deficiency phenotype. This second report of the m.12316G>A mutation in a sporadic patient consolidates its pathogenic nature and provides further elements for genetic counselling.
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PMID:The m.12316G>A mutation in the mitochondrial tRNA Leu(CUN) gene is associated with mitochondrial myopathy and respiratory impairment. 2016 8

The m.3243A>G point mutation in the mitochondrial tRNA(Leu(UUR)) (MTTL1) gene is a common cause of mitochondrial DNA disease and is associated with a variety of clinical presentations. A different mutation occurring at the same site - an m.3243A>T transversion - is less prevalent, but has previously been observed in two patients with encephalopathy and lactic acidosis. We report the investigations of a further two patients with the m.3243A>T mutation who presented with either a chronic progressive external ophthalmoplegia (CPEO) phenotype or sensorineural hearing loss, with single fibre mutation studies confirming segregation of the m.3243A>T mutation with COX deficiency.
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PMID:The pathogenic m.3243A>T mitochondrial DNA mutation is associated with a variable neurological phenotype. 2047 Dec 62


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