Autosomal dominant chronic progressive external ophthalmoplegia: A tale of two genomes

1996 ◽  
Vol 40 (5) ◽  
pp. 693-694 ◽  
Author(s):  
Eric A. Shoubridge
Keyword(s):  
Autosomal Dominant ◽  
Progressive External Ophthalmoplegia ◽  
Chronic Progressive External Ophthalmoplegia

Autosomal Dominant Optic Atrophy

2019 ◽  
pp. 29-34
Author(s):  
Matthew J. Thurtell ◽  
Robert L. Tomsak
Keyword(s):  
Differential Diagnosis ◽  
Optic Atrophy ◽  
Autosomal Dominant ◽  
Spastic Paraparesis ◽  
Progressive External Ophthalmoplegia ◽  
Management Approach ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Autosomal Dominant Optic Atrophy ◽  
Dominant Optic Atrophy ◽  
History Of

There is a broad differential diagnosis for bilateral optic neuropathies, including inflammatory, ischemic, compressive, traumatic, nutritional, toxic, and inherited causes. In this chapter, we begin by discussing the approach to the patient who has bilateral symmetric optic neuropathies. We next review the genetic basis, clinical features, and natural history of autosomal dominant optic atrophy. We list other deficits that can occur in up to 20% of patients with this condition, which can include sensorineural hearing loss, ataxia, myopathy, peripheral neuropathy, spastic paraparesis, and chronic progressive external ophthalmoplegia. Lastly, we discuss the evaluation and management approach for autosomal dominant optic atrophy.

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.

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