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Progressive external ophthalmoplegia characterized by multiple deletions of mitochondrial DNA

Unraveling the pathogenesis of human mitochondrial DNA instability and the initiation of a genetic classification

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Abstract

Over the last decade, many sporadic and familial cases have been reported with multiple deletions of mitochondrial DNA (mtDNA) in postmitotic tissues. Most patients suffer from progressive external ophthalmoplegia (PEO) and may have a nuclear gene defect that predisposes to the accumulation of mtDNA deletions. Recently, positional cloning has led to the discovery of mutations in four such nuclear genes. Some mutations are dominant and others recessive. In all autosomal mutations, defective mtDNA replication and/or repair are probably responsible for the generation of secondary mtDNA deletions. There are also data suggestive of a prominent pathogenic role for disturbed nucleotide metabolism. We here present a tentative genotype-phenotype correlation. Since clinical presentations are heterogeneous and overlap with different previously described clinical syndromes, we advocate the use of a genetic, instead of a clinical, classification of disorders with multiple mtDNA deletions.

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Authors and Affiliations

  1. Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), Born-Bunge Foundation (BBS), University of Antwerp (UIA), Antwerpen, Belgium

    Gert Van Goethem & Christine Van Broeckhoven

  2. Division of Neurology, University Hospital of Antwerp (UZA), Antwerpen, Belgium

    Gert Van Goethem & Jean-Jacques Martin

  3. Department of Neuropathology, Born-Bunge Foundation (BBS), University of Antwerp (UIA), Antwerpen, Belgium

    Jean-Jacques Martin

Authors
  1. Gert Van Goethem
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  2. Jean-Jacques Martin
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  3. Christine Van Broeckhoven
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Correspondence to Christine Van Broeckhoven.

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Van Goethem, G., Martin, JJ. & Van Broeckhoven, C. Progressive external ophthalmoplegia characterized by multiple deletions of mitochondrial DNA. Neuromol Med 3, 129–146 (2003). https://doi.org/10.1385/NMM:3:3:129

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  • DOI: https://doi.org/10.1385/NMM:3:3:129

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