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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Ophthalmoplegia, Chronic Progressive External

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Disease relevance of Ophthalmoplegia, Chronic Progressive External


High impact information on Ophthalmoplegia, Chronic Progressive External

  • Screening of the gene encoding Twinkle in individuals with autosomal dominant progressive external ophthalmoplegia (adPEO), associated with multiple mtDNA deletions, identified 11 different coding-region mutations co-segregating with the disorder in 12 adPEO pedigrees of various ethnic origins [6].
  • One of three loci previously associated with autosomal dominant progressive external ophthalmoplegia (adPEO) encodes ANT1, a mitochondrial nucleotide transporter [7].
  • The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested [8].
  • Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively [8].
  • Previously, we have shown that different mutations in this same gene cause autosomal dominant progressive external ophthalmoplegia (adPEO) with multiple mtDNA deletions (MIM 606075), a neuromuscular disorder sharing a spectrum of symptoms with IOSCA [9].

Chemical compound and disease context of Ophthalmoplegia, Chronic Progressive External

  • Exercise-induced increases in plasma lactate correlated with muscle mutation load in CPEO patients (r = 0.95; p < 0.005) [10].
  • These findings suggest that evolutionarily conserved regions in mitochondrial tRNA genes can exhibit a significant polymorphism in humans, and that the mutation at np 12,308 in the tRNA(Leu(CUN)) gene is unlikely to be associated with CPEO and Wolfram syndrome [11].
  • Mutation of Tyr955 in pol gamma causes the degenerative disease progressive external ophthalmoplegia in humans, and we show that this residue partially accounts for the ability of pol gamma to incorporate D4T-MP and carbovir [12].
  • In the present study free, phosphorylated and total creatine concentrations as well as Mi-CK activity were determined in muscle samples of six patients with chronic progressive external ophthalmoplegia (CPEO) [13].
  • The aim of the present investigation was to study insulin sensitivity index (SI), insulin secretion (AIR(Glucose)), and glucose effectiveness (Sg) in patients with CPEO [14].

Biological context of Ophthalmoplegia, Chronic Progressive External


Anatomical context of Ophthalmoplegia, Chronic Progressive External


Gene context of Ophthalmoplegia, Chronic Progressive External

  • Mean complex I polymorphic frequencies in cytopathic (CPEO, MERRF, MELAS and LHON collectively) patients and in LHON patients differed significantly from controls (P < or = 0.05, t) [22].
  • Twinkle is a nuclear-encoded mtDNA helicase, dominant mutations of which cause adult-onset progressive external ophthalmoplegia (PEO) with multiple mtDNA deletions [23].
  • Eliminating the Ant1 isoform produces a mouse with CPEO pathology but normal ocular motility [24].
  • In the light of these findings, we suggest that the increase in expression of Mn-SOD, ROS production and oxidative damage in affected tissues may play an important role in the pathogenesis and progression of the CPEO syndrome [20].
  • Of the patients referred for KSS and CPEO, 17.72% had deletions/rearrangements [25].

Analytical, diagnostic and therapeutic context of Ophthalmoplegia, Chronic Progressive External

  • In patients with CPEO/KSS, stainings of Mb, SOD, CAT, and GSH-Px in nonatrophic ragged-red fibers (RRFs) were more intense than those in non-RRFs [26].


  1. Clinical and biochemical correlations in mitochondrial myopathies treated with coenzyme Q10. Bresolin, N., Bet, L., Binda, A., Moggio, M., Comi, G., Nador, F., Ferrante, C., Carenzi, A., Scarlato, G. Neurology (1988) [Pubmed]
  2. CPEO associated with a single nucleotide deletion in the mitochondrial tRNA(Tyr) gene. Raffelsberger, T., Rossmanith, W., Thaller-Antlanger, H., Bittner, R.E. Neurology (2001) [Pubmed]
  3. Cricopharyngeal achalasia is a common cause of dysphagia in patients with mtDNA deletions. Kornblum, C., Broicher, R., Walther, E., Seibel, P., Reichmann, H., Klockgether, T., Herberhold, C., Schröder, R. Neurology (2001) [Pubmed]
  4. Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNA. Mariotti, C., Savarese, N., Suomalainen, A., Rimoldi, M., Comi, G., Prelle, A., Antozzi, C., Servidei, S., Jarre, L., DiDonato, S. J. Neurol. (1995) [Pubmed]
  5. Apoptosis is suspended in muscle of mitochondrial encephalomyopathies. Ikezoe, K., Nakagawa, M., Yan, C., Kira, J., Goto, Y., Nonaka, I. Acta Neuropathol. (2002) [Pubmed]
  6. Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Spelbrink, J.N., Li, F.Y., Tiranti, V., Nikali, K., Yuan, Q.P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L., Santoro, L., Toscano, A., Fabrizi, G.M., Somer, H., Croxen, R., Beeson, D., Poulton, J., Suomalainen, A., Jacobs, H.T., Zeviani, M., Larsson, C. Nat. Genet. (2001) [Pubmed]
  7. A helicase is born. Moraes, C.T. Nat. Genet. (2001) [Pubmed]
  8. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Goto, Y., Nonaka, I., Horai, S. Nature (1990) [Pubmed]
  9. Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. Nikali, K., Suomalainen, A., Saharinen, J., Kuokkanen, M., Spelbrink, J.N., Lönnqvist, T., Peltonen, L. Hum. Mol. Genet. (2005) [Pubmed]
  10. Oxidative capacity correlates with muscle mutation load in mitochondrial myopathy. Jeppesen, T.D., Schwartz, M., Olsen, D.B., Vissing, J. Ann. Neurol. (2003) [Pubmed]
  11. Mutations in mitochondrial tRNA genes: non-linkage with syndromes of Wolfram and chronic progressive external ophthalmoplegia. van den Ouweland, J.M., Bruining, G.J., Lindhout, D., Wit, J.M., Veldhuyzen, B.F., Maassen, J.A. Nucleic Acids Res. (1992) [Pubmed]
  12. Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs. Lim, S.E., Ponamarev, M.V., Longley, M.J., Copeland, W.C. J. Mol. Biol. (2003) [Pubmed]
  13. Mitochondrial creatine kinase containing crystals, creatine content and mitochondrial creatine kinase activity in chronic progressive external ophthalmoplegia. Smeitink, J., Stadhouders, A., Sengers, R., Ruitenbeek, W., Wevers, R., ter Laak, H., Trijbels, F. Neuromuscul. Disord. (1992) [Pubmed]
  14. Impaired glucose effectiveness in chronic progressive external ophthalmoplegia. Becker, R., Laube, H., Laube, H., Linn, T., Pabst, W., Damian, M.S. Metab. Clin. Exp. (2002) [Pubmed]
  15. Human extraocular muscles in mitochondrial diseases: comparing chronic progressive external ophthalmoplegia with Leber's hereditary optic neuropathy. Carta, A., Carelli, V., D'Adda, T., Ross-Cisneros, F.N., Sadun, A.A. The British journal of ophthalmology. (2005) [Pubmed]
  16. Clinical and molecular features of adPEO due to mutations in the Twinkle gene. Lewis, S., Hutchison, W., Thyagarajan, D., Dahl, H.H. J. Neurol. Sci. (2002) [Pubmed]
  17. The role of mitochondrial DNA rearrangements in aging and human diseases. Osiewacz, H.D., Hermanns, J. Aging (Milan, Italy) (1992) [Pubmed]
  18. "All-or-none" cytochrome c oxidase positivity in mitochondria in chronic progressive external ophthalmoplegia: an ultrastructural--cytochemical study. Matsuoka, T., Goto, Y., Nonaka, I. Muscle Nerve (1993) [Pubmed]
  19. Apoptosis-related changes in skeletal muscles of patients with mitochondrial diseases. Umaki, Y., Mitsui, T., Endo, I., Akaike, M., Matsumoto, T. Acta Neuropathol. (2002) [Pubmed]
  20. Increased expression of manganese-superoxide dismutase in fibroblasts of patients with CPEO syndrome. Lu, C.Y., Wang, E.K., Lee, H.C., Tsay, H.J., Wei, Y.H. Mol. Genet. Metab. (2003) [Pubmed]
  21. Reduced brain stem excitability in mitochondrial myopathy: evidence for early detection with blink reflex habituation studies. Koutroumanidis, M., Papadimitriou, A., Bouzas, E., Avramidis, T., Papathanassopoulos, P., Howard, R.S., Papapetropoulos, T. Muscle Nerve (1996) [Pubmed]
  22. Mitochondrial DNA polymorphism in disease: a possible contributor to respiratory dysfunction. Lertrit, P., Kapsa, R.M., Jean-Francois, M.J., Thyagarajan, D., Noer, A.S., Marzuki, S., Byrne, E. Hum. Mol. Genet. (1994) [Pubmed]
  23. Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Tyynismaa, H., Mjosund, K.P., Wanrooij, S., Lappalainen, I., Ylikallio, E., Jalanko, A., Spelbrink, J.N., Paetau, A., Suomalainen, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  24. Eliminating the Ant1 isoform produces a mouse with CPEO pathology but normal ocular motility. Yin, H., Stahl, J.S., Andrade, F.H., McMullen, C.A., Webb-Wood, S., Newman, N.J., Biousse, V., Wallace, D.C., Pardue, M.T. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  25. Diagnostic screening of mitochondrial DNA mutations in Australian adults 1990-2001. Marotta, R., Chin, J., Quigley, A., Katsabanis, S., Kapsa, R., Byrne, E., Collins, S. Internal medicine journal. (2004) [Pubmed]
  26. Overexpressions of myoglobin and antioxidant enzymes in ragged-red fibers of skeletal muscle from patients with mitochondrial encephalomyopathy. Kunishige, M., Mitsui, T., Akaike, M., Kawajiri, M., Shono, M., Kawai, H., Matsumoto, T. Muscle Nerve (2003) [Pubmed]
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