mtDNA depletion and impairment of mitochondrial function in a case of a multisystem disorder including severe myopathy.
The ratio of mtDNA and a nuclear reference gene was estimated by Southern blotting in the skeletal muscle DNA of a 3-year-old girl who suffered from congenital brain damage, focal epilepsy, hepatomegaly, malabsorption syndrome and severe myopathy. The signal ratio of mtDNA versus 18S rDNA was 22% of the mean value obtained from controls. No major deletions or insertions were found and the MERRF, MELAS and NARP mutations were ruled out. Mitochondrial DNA-encoded enzyme activities and mitochondrial respiration were reduced. The analysis of the NAD(P)H and flavoprotein redox states of intact fibres revealed the presence of mitochondrial dysfunction. In tissue sections a moderate elevation of type I and type II fibre diameter variation was detected, aberrant NADH- and succinate dehydrogenase staining and some ragged red fibres. This suggested that a mitochondrial disorder caused by a decrease in the amount of intact wild-type mtDNA was responsible for the severe myopathy.
Kirches
E J
EJ
Institut für Neuropathologie, Universität Magdeburg, Germany.
Winkler
K
K
Warich-Kirches
M
M
Szibor
R
R
Wien
F
F
Kunz
W S
WS
von Bossanyi
P
P
Bajaj
P K
PK
Dietzmann
K
K
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001927:Brain Diseases / Q000235:genetics; D004272:DNA, Mitochondrial; D005260:Female; D006801:Humans; D007223:Infant; D017240:Mitochondrial Myopathies / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D017384:Sequence Deletion
D004272:DNA, Mitochondrial