Myoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency

Neuropathology, biochemistry, and molecular genetics

A. Lombes, J. R. Mendell, H. Nakase, R. J. Barohn, E. Bonilla, M. Zeviani, A. J. Yates, J. Omerza, T. L. Gales, K. Nakahara, R. Rizzuto, W. K. Engel, S. DiMauro

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

A 36-year-old man with myoclonic epilepsy and ragged-red fibers (MERRF) died after more than 18 years of follow-up study. He was 1 of 3 affected siblings and the offspring of an affected mother, suggesting maternal transmission. At autopsy, there was neuronal loss and gliosis in the dentate nucleus of the cerebellum and in the inferior olivary nucleus. Skeletal muscle showed ragged-red fibers, and paracrystalline inclusions in mitochondria by electron microscopy. Biochemical analysis showed a generalized partial defect of cytochrome c oxidase (COX) in mitochondria isolated from all tissues, including brain, heart, skeletal muscle, kidney, and liver. The Michaelis constant (Km) for cytochrome c was abnormally low, suggesting a defect of the mitochondrially encoded subunit II of COX. Immunological studies (enzyme-linked immunosorbent assay, dot-blot, Western blot, and immunohistochemistry) showed that the holoenzyme was decreased but subunit II was decreased more than the holocomplex or the nuclearly encoded subunit IV. However, Northern and Southern blots showed that the gene for subunit II, as well as the genes for subunits I, III, IV, and VIII, were of normal size and were normally transcribed. A point mutation or a small deletion of mitochondrial DNA, probably affecting the COX-II gene, may be responsible for the COX deficiency in this case of MERRF.

Original languageEnglish
Pages (from-to)20-33
Number of pages14
JournalAnnals of Neurology
Volume26
Issue number1
Publication statusPublished - 1989

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MERRF Syndrome
Cytochrome-c Oxidase Deficiency
Biochemistry
Molecular Biology
Oxidoreductases
Mitochondria
Skeletal Muscle
Mothers
Olivary Nucleus
Genes
Cerebellar Nuclei
Holoenzymes
Gliosis
Electron Transport Complex IV
Southern Blotting
Cytochromes c
Mitochondrial DNA
Point Mutation
Northern Blotting
Cerebellum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lombes, A., Mendell, J. R., Nakase, H., Barohn, R. J., Bonilla, E., Zeviani, M., ... DiMauro, S. (1989). Myoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency: Neuropathology, biochemistry, and molecular genetics. Annals of Neurology, 26(1), 20-33.

Myoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency : Neuropathology, biochemistry, and molecular genetics. / Lombes, A.; Mendell, J. R.; Nakase, H.; Barohn, R. J.; Bonilla, E.; Zeviani, M.; Yates, A. J.; Omerza, J.; Gales, T. L.; Nakahara, K.; Rizzuto, R.; Engel, W. K.; DiMauro, S.

In: Annals of Neurology, Vol. 26, No. 1, 1989, p. 20-33.

Research output: Contribution to journalArticle

Lombes, A, Mendell, JR, Nakase, H, Barohn, RJ, Bonilla, E, Zeviani, M, Yates, AJ, Omerza, J, Gales, TL, Nakahara, K, Rizzuto, R, Engel, WK & DiMauro, S 1989, 'Myoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency: Neuropathology, biochemistry, and molecular genetics', Annals of Neurology, vol. 26, no. 1, pp. 20-33.
Lombes, A. ; Mendell, J. R. ; Nakase, H. ; Barohn, R. J. ; Bonilla, E. ; Zeviani, M. ; Yates, A. J. ; Omerza, J. ; Gales, T. L. ; Nakahara, K. ; Rizzuto, R. ; Engel, W. K. ; DiMauro, S. / Myoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency : Neuropathology, biochemistry, and molecular genetics. In: Annals of Neurology. 1989 ; Vol. 26, No. 1. pp. 20-33.
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