Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearne-Sayre syndrome

C. T. Moraes, S. DiMauro, M. Zeviani, A. Lombes, S. Shanske, A. F. Miranda, H. Nakase, E. Bonilla, L. C. Werneck, S. Servidei, I. Nonaka, Y. Koga, A. J. Spiro, A. K W Brownell, B. Schmidt, D. L. Schotland, M. Zupanc, D. C. DeVivo

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Abstract

We investigated the correlations of deletions of mitochondrial DNA in skeletal muscle with clinical manifestations of mitochondrial myopathies, a group of disorders defined either by biochemical abnormalities of mitochondria or by morphologic changes causing a ragged red appearance of the muscle fibers histochemically. We performed genomic Southern blot analysis of muscle mitochondrial DNA from 123 patients with different mitochondrial myopathies or encephalomyopathies. Deletions were found in the mitochondrial DNA of 32 patients, all of whom had progressive external ophthalmoplegia. Some patients had only ocular myopathy, whereas others had Kearns-Sayre syndrome, a multisystem disorder characterized by ophthalmoplegia, pigmentary retinopathy, heart block, and cerebral ataxia. The deletions ranged in size from 1.3 to 7.6 kilobases and were mapped to different sites in the mitochondrial DNA, but an identical 4.9-kilobase deletion was found in the same location in 11 patients. Biochemical analysis showed decreased activities of NADH dehydrogenase, rotenone-sensitive NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase, four enzymes of the mitochondrial respiratory chain containing subunits encoded by mitochondrial DNA. We conclude that deletions of muscle mitochondrial DNA are associated with ophthalmoplegia and may result in impaired mitochondrial function. However, the precise relation between clinical and biochemical phenotypes and deletions remains to be defined.

Original languageEnglish (US)
Pages (from-to)1293-1299
Number of pages7
JournalNew England Journal of Medicine
Volume320
Issue number20
StatePublished - 1989
Externally publishedYes

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Chronic Progressive External Ophthalmoplegia
Mitochondrial DNA
Mitochondrial Myopathies
NADH Dehydrogenase
Ophthalmoplegia
Succinate Cytochrome c Oxidoreductase
Kearns-Sayre Syndrome
Mitochondrial Encephalomyopathies
Slow-Twitch Muscle Fibers
Rotenone
Muscles
Heart Block
Retinitis Pigmentosa
Muscular Diseases
Electron Transport Complex IV
Ataxia
Electron Transport
Southern Blotting
Mitochondria
Skeletal Muscle

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Moraes, C. T., DiMauro, S., Zeviani, M., Lombes, A., Shanske, S., Miranda, A. F., ... DeVivo, D. C. (1989). Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearne-Sayre syndrome. New England Journal of Medicine, 320(20), 1293-1299.

Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearne-Sayre syndrome. / Moraes, C. T.; DiMauro, S.; Zeviani, M.; Lombes, A.; Shanske, S.; Miranda, A. F.; Nakase, H.; Bonilla, E.; Werneck, L. C.; Servidei, S.; Nonaka, I.; Koga, Y.; Spiro, A. J.; Brownell, A. K W; Schmidt, B.; Schotland, D. L.; Zupanc, M.; DeVivo, D. C.

In: New England Journal of Medicine, Vol. 320, No. 20, 1989, p. 1293-1299.

Research output: Contribution to journalArticle

Moraes, CT, DiMauro, S, Zeviani, M, Lombes, A, Shanske, S, Miranda, AF, Nakase, H, Bonilla, E, Werneck, LC, Servidei, S, Nonaka, I, Koga, Y, Spiro, AJ, Brownell, AKW, Schmidt, B, Schotland, DL, Zupanc, M & DeVivo, DC 1989, 'Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearne-Sayre syndrome', New England Journal of Medicine, vol. 320, no. 20, pp. 1293-1299.
Moraes CT, DiMauro S, Zeviani M, Lombes A, Shanske S, Miranda AF et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearne-Sayre syndrome. New England Journal of Medicine. 1989;320(20):1293-1299.
Moraes, C. T. ; DiMauro, S. ; Zeviani, M. ; Lombes, A. ; Shanske, S. ; Miranda, A. F. ; Nakase, H. ; Bonilla, E. ; Werneck, L. C. ; Servidei, S. ; Nonaka, I. ; Koga, Y. ; Spiro, A. J. ; Brownell, A. K W ; Schmidt, B. ; Schotland, D. L. ; Zupanc, M. ; DeVivo, D. C. / Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearne-Sayre syndrome. In: New England Journal of Medicine. 1989 ; Vol. 320, No. 20. pp. 1293-1299.
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abstract = "We investigated the correlations of deletions of mitochondrial DNA in skeletal muscle with clinical manifestations of mitochondrial myopathies, a group of disorders defined either by biochemical abnormalities of mitochondria or by morphologic changes causing a ragged red appearance of the muscle fibers histochemically. We performed genomic Southern blot analysis of muscle mitochondrial DNA from 123 patients with different mitochondrial myopathies or encephalomyopathies. Deletions were found in the mitochondrial DNA of 32 patients, all of whom had progressive external ophthalmoplegia. Some patients had only ocular myopathy, whereas others had Kearns-Sayre syndrome, a multisystem disorder characterized by ophthalmoplegia, pigmentary retinopathy, heart block, and cerebral ataxia. The deletions ranged in size from 1.3 to 7.6 kilobases and were mapped to different sites in the mitochondrial DNA, but an identical 4.9-kilobase deletion was found in the same location in 11 patients. Biochemical analysis showed decreased activities of NADH dehydrogenase, rotenone-sensitive NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase, four enzymes of the mitochondrial respiratory chain containing subunits encoded by mitochondrial DNA. We conclude that deletions of muscle mitochondrial DNA are associated with ophthalmoplegia and may result in impaired mitochondrial function. However, the precise relation between clinical and biochemical phenotypes and deletions remains to be defined.",
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AU - Moraes, C. T.

AU - DiMauro, S.

AU - Zeviani, M.

AU - Lombes, A.

AU - Shanske, S.

AU - Miranda, A. F.

AU - Nakase, H.

AU - Bonilla, E.

AU - Werneck, L. C.

AU - Servidei, S.

AU - Nonaka, I.

AU - Koga, Y.

AU - Spiro, A. J.

AU - Brownell, A. K W

AU - Schmidt, B.

AU - Schotland, D. L.

AU - Zupanc, M.

AU - DeVivo, D. C.

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N2 - We investigated the correlations of deletions of mitochondrial DNA in skeletal muscle with clinical manifestations of mitochondrial myopathies, a group of disorders defined either by biochemical abnormalities of mitochondria or by morphologic changes causing a ragged red appearance of the muscle fibers histochemically. We performed genomic Southern blot analysis of muscle mitochondrial DNA from 123 patients with different mitochondrial myopathies or encephalomyopathies. Deletions were found in the mitochondrial DNA of 32 patients, all of whom had progressive external ophthalmoplegia. Some patients had only ocular myopathy, whereas others had Kearns-Sayre syndrome, a multisystem disorder characterized by ophthalmoplegia, pigmentary retinopathy, heart block, and cerebral ataxia. The deletions ranged in size from 1.3 to 7.6 kilobases and were mapped to different sites in the mitochondrial DNA, but an identical 4.9-kilobase deletion was found in the same location in 11 patients. Biochemical analysis showed decreased activities of NADH dehydrogenase, rotenone-sensitive NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase, four enzymes of the mitochondrial respiratory chain containing subunits encoded by mitochondrial DNA. We conclude that deletions of muscle mitochondrial DNA are associated with ophthalmoplegia and may result in impaired mitochondrial function. However, the precise relation between clinical and biochemical phenotypes and deletions remains to be defined.

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