NeuroMolecular Medicine

, Volume 3, Issue 3, pp 129–146

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
  • Gert Van Goethem
  • Jean-Jacques Martin
  • Christine Van Broeckhoven
Review Article

DOI: 10.1385/NMM:3:3:129

Cite this article as:
Van Goethem, G., Martin, JJ. & Van Broeckhoven, C. Neuromol Med (2003) 3: 129. doi:10.1385/NMM:3:3:129

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.

Index Entries

Progressive external ophthalmoplegia mitochondrial DNA polymerase gamma twinkle adenine nucleotide translocator 1 thymidine phosphorylase nucleotides 

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Gert Van Goethem
    • 1
    • 2
  • Jean-Jacques Martin
    • 2
    • 3
  • Christine Van Broeckhoven
    • 1
  1. 1.Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), Born-Bunge Foundation (BBS)University of Antwerp (UIA)AntwerpenBelgium
  2. 2.Division of NeurologyUniversity Hospital of Antwerp (UZA)AntwerpenBelgium
  3. 3.Department of Neuropathology, Born-Bunge Foundation (BBS)University of Antwerp (UIA)AntwerpenBelgium

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