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Single deletions in mitochondrial DNA--molecular mechanisms and disease phenotypes in clinical practice.

Pitceathly, RD; Rahman, S; Hanna, MG; (2012) Single deletions in mitochondrial DNA--molecular mechanisms and disease phenotypes in clinical practice. Neuromuscular Disorders , 22 (7) 577 - 586. 10.1016/j.nmd.2012.03.009. Green open access

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Abstract

Over 20 years ago single clonal deletions were the first mitochondrial DNA (mtDNA) genetic defects described in association with human disease. Since then very large numbers of children and adults harbouring such deletions have been described and it is clear they are an important cause of human mitochondrial disease. However, there still remain many important challenges in relation to our understanding of mechanisms leading to deletion formation and propagation and in relation to the factors determining the complex and varying relationship between genotype and clinical phenotype. Although multidisciplinary team care is essential and can improve quality of life and outcomes for patients, a definitive molecular treatment for single mtDNA deletions remains an important translational research goal. Patients with mtDNA deletions exhibit a very wide range of different clinical phenotypes with marked variation in age at onset and disease severity. Single mtDNA deletions may enter into the differential diagnosis of many different paediatric and adult presentations across a wide range of medical specialties, although neurological presentations are amongst the most common. In this review, we examine the molecular mechanisms underpinning mtDNA replication and we consider the hypotheses proposed to explain the formation and propagation of single large-scale mtDNA deletions. We also describe the range of clinical features associated with single mtDNA deletions, outline a molecular diagnostic approach and discuss current management including the role of aerobic and resistance exercise training programmes.

Type: Article
Title: Single deletions in mitochondrial DNA--molecular mechanisms and disease phenotypes in clinical practice.
Location: UK
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.nmd.2012.03.009
Publisher version: http://dx.doi.org/10.1016/j.nmd.2012.03.009
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: DNA, Mitochondrial, Humans, Mitochondrial Diseases, Models, Molecular, Phenotype, Sequence Deletion
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1349925
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