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J Clin Invest. Jul 1992; 90(1): 61–66.
PMCID: PMC443063

Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia.

Abstract

Multiple deletions of mitochondrial DNA (mtDNA) have recently been reported in familial progressive external ophthalmoplegia (PEO), in a case of progressive encephalomyopathy, and in inherited recurrent myoglobinuria. The inheritance of familial PEO has been autosomal dominant, which indicates that a mutation in an unknown nuclear gene results in several mtDNA deletions of different sizes in these patients. We report a patient with autosomal dominant PEO, whose major clinical symptom, however, was severe retarded depression. The morphological analyses of the tissue samples derived from autopsy showed various abnormalities in the mitochondria in all the tissues studied. The activities of the respiratory chain enzymes encoded by mtDNA were remarkably reduced in the skeletal muscle. The mtDNA analyses confirmed that besides myopathy, this patient had a multisystem disorder with widespread distribution of multiple deletions of mtDNA. The highest percentage of mutated mtDNA was found in the brain, skeletal muscle and the heart, the relative quantity of mutated mtDNA correlating to the severity of the clinical symptoms.

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Selected References

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  • Holt IJ, Harding AE, Morgan-Hughes JA. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature. 1988 Feb 25;331(6158):717–719. [PubMed]
  • Ozawa T, Yoneda M, Tanaka M, Ohno K, Sato W, Suzuki H, Nishikimi M, Yamamoto M, Nonaka I, Horai S. Maternal inheritance of deleted mitochondrial DNA in a family with mitochondrial myopathy. Biochem Biophys Res Commun. 1988 Aug 15;154(3):1240–1247. [PubMed]
  • Moraes CT, DiMauro S, Zeviani M, Lombes A, Shanske S, Miranda AF, Nakase H, Bonilla E, Werneck LC, Servidei S, et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med. 1989 May 18;320(20):1293–1299. [PubMed]
  • Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon EA, Rowland LP. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology. 1988 Sep;38(9):1339–1346. [PubMed]
  • Rotig A, Colonna M, Bonnefont JP, Blanche S, Fischer A, Saudubray JM, Munnich A. Mitochondrial DNA deletion in Pearson's marrow/pancreas syndrome. Lancet. 1989 Apr 22;1(8643):902–903. [PubMed]
  • Zeviani M, Servidei S, Gellera C, Bertini E, DiMauro S, DiDonato S. An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature. 1989 May 25;339(6222):309–311. [PubMed]
  • Zeviani M, Bresolin N, Gellera C, Bordoni A, Pannacci M, Amati P, Moggio M, Servidei S, Scarlato G, DiDonato S. Nucleus-driven multiple large-scale deletions of the human mitochondrial genome: a new autosomal dominant disease. Am J Hum Genet. 1990 Dec;47(6):904–914. [PMC free article] [PubMed]
  • Servidei S, Zeviani M, Manfredi G, Ricci E, Silvestri G, Bertini E, Gellera C, Di Mauro S, Di Donato S, Tonali P. Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies. Neurology. 1991 Jul;41(7):1053–1059. [PubMed]
  • Yuzaki M, Ohkoshi N, Kanazawa I, Kagawa Y, Ohta S. Multiple deletions in mitochondrial DNA at direct repeats of non-D-loop regions in cases of familial mitochondrial myopathy. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1352–1357. [PubMed]
  • Cormier V, Rotig A, Tardieu M, Colonna M, Saudubray JM, Munnich A. Autosomal dominant deletions of the mitochondrial genome in a case of progressive encephalomyopathy. Am J Hum Genet. 1991 Apr;48(4):643–648. [PMC free article] [PubMed]
  • Ohno K, Tanaka M, Sahashi K, Ibi T, Sato W, Yamamoto T, Takahashi A, Ozawa T. Mitochondrial DNA deletions in inherited recurrent myoglobinuria. Ann Neurol. 1991 Apr;29(4):364–369. [PubMed]
  • Poulton J, Deadman ME, Ramacharan S, Gardiner RM. Germ-line deletions of mtDNA in mitochondrial myopathy. Am J Hum Genet. 1991 Apr;48(4):649–653. [PMC free article] [PubMed]
  • Bookelman H, Trijbels JM, Sengers RC, Janssen AJ, Veerkamp JH, Stadhouders AM. Pyruvate oxidation in rat and human skeletal muscle mitochondria. Biochem Med. 1978 Dec;20(3):395–403. [PubMed]
  • Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM, Sengers RC, Janssen AJ. Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta. 1985 Nov 29;153(1):23–36. [PubMed]
  • Ackrell BA, Kearney EB, Singer TP. Mammalian succinate dehydrogenase. Methods Enzymol. 1978;53:466–483. [PubMed]
  • Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457–465. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Feinberg AP, Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Shoffner JM, Lott MT, Voljavec AS, Soueidan SA, Costigan DA, Wallace DC. Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7952–7956. [PMC free article] [PubMed]
  • Clayton DA. Replication of animal mitochondrial DNA. Cell. 1982 Apr;28(4):693–705. [PubMed]
  • Schon EA, Rizzuto R, Moraes CT, Nakase H, Zeviani M, DiMauro S. A direct repeat is a hotspot for large-scale deletion of human mitochondrial DNA. Science. 1989 Apr 21;244(4902):346–349. [PubMed]
  • Johns DR, Rutledge SL, Stine OC, Hurko O. Directly repeated sequences associated with pathogenic mitochondrial DNA deletions. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8059–8062. [PMC free article] [PubMed]
  • Mita S, Rizzuto R, Moraes CT, Shanske S, Arnaudo E, Fabrizi GM, Koga Y, DiMauro S, Schon EA. Recombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNA. Nucleic Acids Res. 1990 Feb 11;18(3):561–567. [PMC free article] [PubMed]
  • Cortopassi GA, Arnheim N. Detection of a specific mitochondrial DNA deletion in tissues of older humans. Nucleic Acids Res. 1990 Dec 11;18(23):6927–6933. [PMC free article] [PubMed]

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