Increased mitochondrial DNA deletions in the skeletal muscle of myotonic dystrophy.

Abstract:

:Mitochondrial abnormality in the skeletal muscles of 13 patients with myotonic dystrophy was analyzed by both histochemical and molecular biologic methods. Nine of 13 patients had ragged-red fibers (50 +/- 116 per 10,000 muscle fibers, mean +/- SD), and 10 patients had cytochrome c oxidase-negative fibers (41 +/- 90 per 10,000 muscle fibers). Southern blot analysis detected no mitochondrial DNA deletions, while PCR revealed multiple mitochondrial DNA deletions in all the specimens. Direct sequencing of one of the deleted mitochondrial DNAs disclosed that the junctional sequence of a 3,460-bp deletion involved a 6-bp directly repeated sequence (5'-TAGAAG-3') flanked by C-rich regions located on the CO3 gene and the ND5 gene. Quantitative analysis of PCR amplified deleted mitochondrial DNAs revealed that the amount of deleted mitochondrial DNAs had positive correlation both with the frequencies of ragged-red fibers and cytochrome c oxidase-negative fibers. Although deleted mitochondrial DNAs were observed even in controls above age 30, the mean amount of deleted mitochondrial DNAs in patients with myotonic dystrophy was significantly higher than in controls. Moreover, the increase of deleted mitochondrial DNAs with aging was more marked in myotonic dystrophy than in controls. These results suggest that increased mitochondrial DNA deletions and consequent impairment of mitochondrial function contribute to the pathophysiology of myotonic dystrophy.

journal_name

Gerontology

journal_title

Gerontology

authors

Sahashi K,Tanaka M,Tashiro M,Ohno K,Ibi T,Takahashi A,Ozawa T

doi

10.1159/000213303

keywords:

subject

Has Abstract

pub_date

1992-01-01 00:00:00

pages

18-29

issue

1-2

eissn

0304-324X

issn

1423-0003

journal_volume

38

pub_type

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