scholarly journals Chronic progressive external ophthalmoplegia in a Saudi patient with a mutation in the POLG gene successfully managed with bilateral frontalis sling

2021 ◽  
Vol 18 (2) ◽  
pp. 121-126
Author(s):  
Hussein Algahtani ◽  
Bader Shirah ◽  
Khalid Alsaggaf ◽  
Mohammad H. Al-Qahtani ◽  
Angham Abdulrahman Abdulkareem ◽  
...  
Keyword(s):  
Progressive External Ophthalmoplegia ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Polg Gene

Multiple sclerosis and chronic progressive external ophthalmoplegia associated with a large scale mitochondrial DNA single deletion

2016 ◽  
Vol 263 (7) ◽  
pp. 1449-1451 ◽  
Author(s):  
Lorenzo Gaetani ◽  
Andrea Mignarri ◽  
Maria Di Gregorio ◽  
Paola Sarchielli ◽  
Alessandro Malandrini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mitochondrial Dna ◽  
Large Scale ◽  
Progressive External Ophthalmoplegia ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Single Deletion

scholarly journals Concerted action of two novel tRNA mtDNA point mutations in chronic progressive external ophthalmoplegia

2008 ◽  
Vol 28 (2) ◽  
pp. 89-96 ◽  
Author(s):  
Cornelia Kornblum ◽  
Gábor Zsurka ◽  
Rudolf J. Wiesner ◽  
Rolf Schröder ◽  
Wolfram S. Kunz
Keyword(s):  
Skeletal Muscle ◽  
Northern Blot ◽  
Phenotypic Expression ◽  
Point Mutations ◽  
Skeletal Muscle Fibre ◽  
Progressive External Ophthalmoplegia ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Mtdna Mutations ◽  
Mtdna Sequence ◽  
Functional Consequences

CPEO (chronic progressive external ophthalmoplegia) is a common mitochondrial disease phenotype in adults which is due to mtDNA (mitochondrial DNA) point mutations in a subset of patients. Attributing pathogenicity to novel tRNA mtDNA mutations still poses a challenge, particularly when several mtDNA sequence variants are present. In the present study we report a CPEO patient for whom sequencing of the mitochondrial genome revealed three novel tRNA mtDNA mutations: G5835A, del4315A, T1658C in tRNATyr, tRNAIle and tRNAVal genes. In skeletal muscle, the tRNAVal and tRNAIle mutations were homoplasmic, whereas the tRNATyr mutation was heteroplasmic. To address the pathogenic relevance, we performed two types of functional tests: (i) single skeletal muscle fibre analysis comparing G5835A mutation loads and biochemical phenotypes of corresponding fibres, and (ii) Northern-blot analyses of mitochondrial tRNATyr, tRNAIle and tRNAVal. We demonstrated that both the G5835A tRNATyr and del4315A tRNAIle mutation have serious functional consequences. Single-fibre analyses displayed a high threshold of the tRNATyr mutation load for biochemical phenotypic expression at the single-cell level, indicating a rather mild pathogenic effect. In contrast, skeletal muscle tissue showed a severe decrease in respiratory-chain activities, a reduced overall COX (cytochrome c oxidase) staining intensity and abundant COX-negative fibres. Northern-blot analyses showed a dramatic reduction of tRNATyr and tRNAIle levels in muscle, with impaired charging of tRNAIle, whereas tRNAVal levels were only slightly decreased, with amino-acylation unaffected. Our findings suggest that the heteroplasmic tRNATyr and homoplasmic tRNAIle mutation act together, resulting in a concerted effect on the biochemical and histological phenotype. Thus homoplasmic mutations may influence the functional consequences of pathogenic heteroplasmic mtDNA mutations.

scholarly journals Chronic progressive external ophthalmoplegia: I. A quantitative histochemical study of skeletal muscles

1988 ◽  
Vol 46 (2) ◽  
pp. 133-142 ◽  
Author(s):  
Elza Dias-Tosta
Keyword(s):  
Enzyme Activity ◽  
Muscle Weakness ◽  
Positive Family History ◽  
Oxidative Enzyme ◽  
Progressive External Ophthalmoplegia ◽  
Muscle Fibres ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Limb Muscle ◽  
Oxidative Enzyme Activity ◽  
Group 2

This study quantitates the major morphological and cytochemical changes in limb muscle biopsies from 37 patients with the, syndrome of chronic progressive external ophthalmoplegia (CPEO). The aim was to assess the value of limb muscle biopsy in the diagnosis of this syndrome; to define the myopathological changes and to determine whether there were any specific clinico-pathological correlations. Patients were divided into three clinical groups - 11 patients with CPEO with facial and/or limb muscle weakness; 10 with CPEO with facial and/or limb muscle weakness and a positive family history; 16 with CPEO with one or more of the following: pigmentary retinopathy, cerebellar ataxia, pyramidal signs and peripheral neuropathy. The following parameters were measured: the proportions of histochemical fibre types, the muscle fibre areas and the percentage of muscle fibres showing increased oxidative enzyme activity. Pooled results for each of the clinical categories were compared. Statistical analysis of fibre areas and the percentage of fibres with increased oxidative enzyme activity, showed that group 2 differed from the others (p < 0.05). Patients in group 2 showed the highest incidence of type 1 fibre hypertrophy, type 2A atrophy and the lowest incidence of fibres with increased oxidative activity. Fibre type disproportions occurred in all three groups but the differences were not significant.

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