scholarly journals Differential Phenotypes of Active Site and Human Autosomal Dominant Progressive External Ophthalmoplegia Mutations in Drosophila Mitochondrial DNA Helicase Expressed in Schneider Cells

2007 ◽  
Vol 282 (13) ◽  
pp. 9436-9444 ◽  
Author(s):  
Yuichi Matsushima ◽  
Laurie S. Kaguni
Keyword(s):  
Mitochondrial Dna ◽  
Active Site ◽  
Autosomal Dominant ◽  
Dna Helicase ◽  
Progressive External Ophthalmoplegia

Mutations of mitochondrial DNA polymerase ?A are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia

2002 ◽  
Vol 52 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Eleonora Lamantea ◽  
Valeria Tiranti ◽  
Andreina Bordoni ◽  
Antonio Toscano ◽  
Francesco Bono ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Dna Polymerase ◽  
Autosomal Dominant ◽  
Progressive External Ophthalmoplegia ◽  
Mitochondrial Dna Polymerase

scholarly journals Clinical, Histological, and Genetic Features of 25 Patients with Autosomal Dominant Progressive External Ophthalmoplegia (ad-PEO)/PEO-Plus Due to TWNK Mutations

2021 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Laura Bermejo-Guerrero ◽  
Carlos Pablo de Fuenmayor-Fernández de la Hoz ◽  
Pablo Serrano-Lorenzo ◽  
Alberto Blázquez-Encinar ◽  
Gerardo Gutiérrez-Gutiérrez ◽  
...  
Keyword(s):  
Family History ◽  
Autosomal Dominant ◽  
Positive Family History ◽  
Dna Helicase ◽  
Exercise Intolerance ◽  
Progressive External Ophthalmoplegia ◽  
Muscle Dystrophy ◽  
Genetic Features ◽  
The Mean ◽  
Muscle Biopsies

Autosomal dominant mutations in the TWNK gene, which encodes a mitochondrial DNA helicase, cause adult-onset progressive external ophthalmoplegia (PEO) and PEO-plus presentations. In this retrospective observational study, we describe clinical and complementary data from 25 PEO patients with mutations in TWNK recruited from the Hospital 12 de Octubre Mitochondrial Disorders Laboratory Database. The mean ages of onset and diagnosis were 43 and 63 years, respectively. Family history was positive in 22 patients. Ptosis and PEO (92% and 80%) were the most common findings. Weakness was present in 48%, affecting proximal limbs, neck, and bulbar muscles. Exercise intolerance was present in 28%. Less frequent manifestations were cardiac (24%) and respiratory (4%) involvement, neuropathy (8%), ataxia (4%), and parkinsonism (4%). Only 28% had mild hyperCKemia. All 19 available muscle biopsies showed signs of mitochondrial dysfunction. Ten different TWNK mutations were identified, with c.1361T>G (p.Val454Gly) and c.1070G>C (p.Arg357Pro) being the most common. Before definitive genetic confirmation, 56% of patients were misdiagnosed (36% with myasthenia, 20% with oculopharyngeal muscle dystrophy). Accurate differential diagnosis and early confirmation with appropriately chosen complementary studies allow genetic counseling and the avoidance of unnecessary treatments. Thus, mitochondrial myopathies must be considered in PEO/PEO-plus presentations, and particularly, TWNK is an important cause when positive family history is present.

scholarly journals Suppression of Mitochondrial DNA Instability of Autosomal Dominant Forms of Progressive External Ophthalmoplegia-Associated ANT1 Mutations in Podospora anserina

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 861-871 ◽  
Author(s):  
Riyad El-Khoury ◽  
Annie Sainsard-Chanet
Keyword(s):  
Mitochondrial Dna ◽  
Membrane Potential ◽  
Large Scale ◽  
Autosomal Dominant ◽  
Adenine Nucleotide ◽  
Podospora Anserina ◽  
Progressive External Ophthalmoplegia ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Mtdna Deletions

Maintenance and expression of mitochondrial DNA (mtDNA) are essential for the cell and the organism. In humans, several mutations in the adenine nucleotide translocase gene ANT1 are associated with multiple mtDNA deletions and autosomal dominant forms of progressive external ophthalmoplegia (adPEO). The mechanisms underlying the mtDNA instability are still obscure. A current hypothesis proposes that these pathogenic mutations primarily uncouple the mitochondrial inner membrane, which secondarily causes mtDNA instability. Here we show that the three adPEO-associated mutations equivalent to A114P, L98P, and V289M introduced into the Podospora anserina ANT1 ortholog dominantly cause severe growth defects, decreased reactive oxygen species production (ROS), decreased mitochondrial inner membrane potential (Δψ), and accumulation of large-scale mtDNA deletions leading to premature death. Interestingly, we show that, at least for the adPEO-type M106P and A121P mutant alleles, the associated mtDNA instability cannot be attributed only to a reduced membrane potential or to an increased ROS level since it can be suppressed without restoration of the Δψ or modification of the ROS production. Suppression of mtDNA instability due to the M106P and A121P mutations was obtained by an allele of the rmp1 gene involved in nucleo-mitochondrial cross- talk and also by an allele of the AS1 gene encoding a cytosolic ribosomal protein. In contrast, the mtDNA instability caused by the S296M mutation was not suppressed by these alleles.

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
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