Abstract
Inclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is based on clinical features and distinctive morphological findings by both light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged-red fibers are common in patients with sporadic inclusion body myositis, and multiple mitochondrial DNA (mtDNA) deletions have been reported in 3 such patients, suggesting that mtDNA mutations may have a pathogenetic role. We studied 56 patients with sporadic inclusion body myositis, using a combination of clinical, morphological, biochemical, and molecular genetic analyses to determine the frequency and the distribution of mtDNA deletions. Using the polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients, compared to 40% of normal age-matched control subjects and 47% of disease control subjects. The presence of deletions correlated with morphological evidence of ragged-red, cytochrome c oxidase-negative fibers, and with defects of complexes I and IV of the electron transport chain. Although aging may account for a proportion of mtDNA deletions in patients with sporadic inclusion body myositis and control subjects, mtDNA alterations may be accelerated in sporadic inclusion body myositis.
| Original language | English |
|---|---|
| Pages (from-to) | 789-795 |
| Number of pages | 7 |
| Journal | Annals of Neurology |
| Volume | 39 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1996 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Multiple mitochondrial DNA deletions in sporadic inclusion body myositis : A study of 56 patients. / Santorelli, F. M.; Sciacco, M.; Tanji, K.; Shanske, S.; Vu, T. H.; Golzi, V.; Griggs, R. C.; Mendell, J. R.; Hays, A. P.; Bertorini, T. E.; Pestronk, A.; Bonilla, E.; DiMauro, S.
In: Annals of Neurology, Vol. 39, No. 6, 06.1996, p. 789-795.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Multiple mitochondrial DNA deletions in sporadic inclusion body myositis
T2 - A study of 56 patients
AU - Santorelli, F. M.
AU - Sciacco, M.
AU - Tanji, K.
AU - Shanske, S.
AU - Vu, T. H.
AU - Golzi, V.
AU - Griggs, R. C.
AU - Mendell, J. R.
AU - Hays, A. P.
AU - Bertorini, T. E.
AU - Pestronk, A.
AU - Bonilla, E.
AU - DiMauro, S.
PY - 1996/6
Y1 - 1996/6
N2 - Inclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is based on clinical features and distinctive morphological findings by both light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged-red fibers are common in patients with sporadic inclusion body myositis, and multiple mitochondrial DNA (mtDNA) deletions have been reported in 3 such patients, suggesting that mtDNA mutations may have a pathogenetic role. We studied 56 patients with sporadic inclusion body myositis, using a combination of clinical, morphological, biochemical, and molecular genetic analyses to determine the frequency and the distribution of mtDNA deletions. Using the polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients, compared to 40% of normal age-matched control subjects and 47% of disease control subjects. The presence of deletions correlated with morphological evidence of ragged-red, cytochrome c oxidase-negative fibers, and with defects of complexes I and IV of the electron transport chain. Although aging may account for a proportion of mtDNA deletions in patients with sporadic inclusion body myositis and control subjects, mtDNA alterations may be accelerated in sporadic inclusion body myositis.
AB - Inclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is based on clinical features and distinctive morphological findings by both light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged-red fibers are common in patients with sporadic inclusion body myositis, and multiple mitochondrial DNA (mtDNA) deletions have been reported in 3 such patients, suggesting that mtDNA mutations may have a pathogenetic role. We studied 56 patients with sporadic inclusion body myositis, using a combination of clinical, morphological, biochemical, and molecular genetic analyses to determine the frequency and the distribution of mtDNA deletions. Using the polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients, compared to 40% of normal age-matched control subjects and 47% of disease control subjects. The presence of deletions correlated with morphological evidence of ragged-red, cytochrome c oxidase-negative fibers, and with defects of complexes I and IV of the electron transport chain. Although aging may account for a proportion of mtDNA deletions in patients with sporadic inclusion body myositis and control subjects, mtDNA alterations may be accelerated in sporadic inclusion body myositis.
UR - http://www.scopus.com/inward/record.url?scp=8944243541&partnerID=8YFLogxK
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U2 - 10.1002/ana.410390615
DO - 10.1002/ana.410390615
M3 - Article
C2 - 8651651
AN - SCOPUS:8944243541
VL - 39
SP - 789
EP - 795
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 6
ER -