Mitochondrial DNA deletions in mitochondrial cytopathies: Observations in 19 patients

M. Yamamoto, P. R. Clemens, Andrew G Engel

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Among 56 patients with mitochondrial myopathies or cytopathies, 19 had large-scale deletions of mitochondrial DNA (mtDNA). Consistent with previous observations, all 19 had progressive external ophthalmoplegia and 12 had complete or partial Kearns-Sayre syndrome. One of two patients in whom mitochondrial rather than whole muscle DNA was analyzed had multiple populations of deleted mtDNA (dmtDNA). In all patients, the length of dmtDNA was inversely related to age of onset, but was not related to multiplicity of organ involvement. Patients with >50% dmtDNA tended to have an earlier onset of symptoms and a higher proportion of ragged-red fibers and cytochrome c oxidase (CCO)-negative fibers than patients with <50% dmtDNA, but these differences did not reach statistical significance. In some patients, CCO- negative fibers were more abundant than ragged-red fibers, indicating that the distribution of abnormal mitochondria can be more widespread than suggested by the frequency of ragged-red fibers. In biochemical assays, citrate synthase activity was a better reference for detecting defects in the respiratory complexes than the wet weight of muscle. Using this reference, 10 of 14 patients had one or more respiratory complex defects, and 74% of the observed defects could be correlated with an appropriate mtDNA deletion.

Original languageEnglish (US)
Pages (from-to)1822-1828
Number of pages7
JournalNeurology
Volume41
Issue number11
StatePublished - 1991

Fingerprint

Mitochondrial DNA
Electron Transport Complex IV
Kearns-Sayre Syndrome
Chronic Progressive External Ophthalmoplegia
Mitochondrial Myopathies
Citrate (si)-Synthase
Muscles
Mitochondrial cytopathy
Age of Onset
Mitochondria
Weights and Measures
DNA
Population

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mitochondrial DNA deletions in mitochondrial cytopathies : Observations in 19 patients. / Yamamoto, M.; Clemens, P. R.; Engel, Andrew G.

In: Neurology, Vol. 41, No. 11, 1991, p. 1822-1828.

Research output: Contribution to journalArticle

Yamamoto, M. ; Clemens, P. R. ; Engel, Andrew G. / Mitochondrial DNA deletions in mitochondrial cytopathies : Observations in 19 patients. In: Neurology. 1991 ; Vol. 41, No. 11. pp. 1822-1828.
@article{7ea910df10a541dc9f8cabd06ffbd636,
title = "Mitochondrial DNA deletions in mitochondrial cytopathies: Observations in 19 patients",
abstract = "Among 56 patients with mitochondrial myopathies or cytopathies, 19 had large-scale deletions of mitochondrial DNA (mtDNA). Consistent with previous observations, all 19 had progressive external ophthalmoplegia and 12 had complete or partial Kearns-Sayre syndrome. One of two patients in whom mitochondrial rather than whole muscle DNA was analyzed had multiple populations of deleted mtDNA (dmtDNA). In all patients, the length of dmtDNA was inversely related to age of onset, but was not related to multiplicity of organ involvement. Patients with >50{\%} dmtDNA tended to have an earlier onset of symptoms and a higher proportion of ragged-red fibers and cytochrome c oxidase (CCO)-negative fibers than patients with <50{\%} dmtDNA, but these differences did not reach statistical significance. In some patients, CCO- negative fibers were more abundant than ragged-red fibers, indicating that the distribution of abnormal mitochondria can be more widespread than suggested by the frequency of ragged-red fibers. In biochemical assays, citrate synthase activity was a better reference for detecting defects in the respiratory complexes than the wet weight of muscle. Using this reference, 10 of 14 patients had one or more respiratory complex defects, and 74{\%} of the observed defects could be correlated with an appropriate mtDNA deletion.",
author = "M. Yamamoto and Clemens, {P. R.} and Engel, {Andrew G}",
year = "1991",
language = "English (US)",
volume = "41",
pages = "1822--1828",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Mitochondrial DNA deletions in mitochondrial cytopathies

T2 - Observations in 19 patients

AU - Yamamoto, M.

AU - Clemens, P. R.

AU - Engel, Andrew G

PY - 1991

Y1 - 1991

N2 - Among 56 patients with mitochondrial myopathies or cytopathies, 19 had large-scale deletions of mitochondrial DNA (mtDNA). Consistent with previous observations, all 19 had progressive external ophthalmoplegia and 12 had complete or partial Kearns-Sayre syndrome. One of two patients in whom mitochondrial rather than whole muscle DNA was analyzed had multiple populations of deleted mtDNA (dmtDNA). In all patients, the length of dmtDNA was inversely related to age of onset, but was not related to multiplicity of organ involvement. Patients with >50% dmtDNA tended to have an earlier onset of symptoms and a higher proportion of ragged-red fibers and cytochrome c oxidase (CCO)-negative fibers than patients with <50% dmtDNA, but these differences did not reach statistical significance. In some patients, CCO- negative fibers were more abundant than ragged-red fibers, indicating that the distribution of abnormal mitochondria can be more widespread than suggested by the frequency of ragged-red fibers. In biochemical assays, citrate synthase activity was a better reference for detecting defects in the respiratory complexes than the wet weight of muscle. Using this reference, 10 of 14 patients had one or more respiratory complex defects, and 74% of the observed defects could be correlated with an appropriate mtDNA deletion.

AB - Among 56 patients with mitochondrial myopathies or cytopathies, 19 had large-scale deletions of mitochondrial DNA (mtDNA). Consistent with previous observations, all 19 had progressive external ophthalmoplegia and 12 had complete or partial Kearns-Sayre syndrome. One of two patients in whom mitochondrial rather than whole muscle DNA was analyzed had multiple populations of deleted mtDNA (dmtDNA). In all patients, the length of dmtDNA was inversely related to age of onset, but was not related to multiplicity of organ involvement. Patients with >50% dmtDNA tended to have an earlier onset of symptoms and a higher proportion of ragged-red fibers and cytochrome c oxidase (CCO)-negative fibers than patients with <50% dmtDNA, but these differences did not reach statistical significance. In some patients, CCO- negative fibers were more abundant than ragged-red fibers, indicating that the distribution of abnormal mitochondria can be more widespread than suggested by the frequency of ragged-red fibers. In biochemical assays, citrate synthase activity was a better reference for detecting defects in the respiratory complexes than the wet weight of muscle. Using this reference, 10 of 14 patients had one or more respiratory complex defects, and 74% of the observed defects could be correlated with an appropriate mtDNA deletion.

UR - http://www.scopus.com/inward/record.url?scp=0025986459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025986459&partnerID=8YFLogxK

M3 - Article

C2 - 1682853

AN - SCOPUS:0025986459

VL - 41

SP - 1822

EP - 1828

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 11

ER -