Premium
Very low levels of the mtDNA A3243G mutation associated with mitochondrial dysfunction in vivo
Author(s) -
Chinnery Patrick F.,
Taylor Doris J.,
Brown Denise T.,
Manners David,
Styles Peter,
Lodi Raffaele
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200003)47:3<381::aid-ana17>3.0.co;2-2
Subject(s) - in vivo , mitochondrial dna , mutation , skeletal muscle , biology , respiratory chain , mitochondrion , melas syndrome , mitochondrial respiratory chain , medicine , endocrinology , genetics , chemistry , gene , mitochondrial myopathy
We studied mitochondrial function in vivo in 2 brothers harboring the mitochondrial DNA A3243G mutation by using magnetic resonance spectroscopy. One brother presented with recurrent strokes and had a mitochondrial respiratory chain complex I defect, with 85% A3243G mutation in his quadriceps. The maximum rate of mitochondrial ATP production in his calf, measured in vivo, was reduced to 21% of the normal mean value. The second brother had mild exercise intolerance, normal muscle histochemistry, and normal respiratory chain activity in vitro. Despite a level of the A3243G mutation of only 5.95% (SD, 4.45; range, 0.7–16.1%) within single muscle fibers from the gastrocnemius muscle, the maximum rate of mitochondrial ATP production in his calf, measured in vivo, was reduced to 35% of the normal mean value. These findings suggest that there may not be a clear genetic threshold level for the expression of the A3243G mutation in skeletal muscle in vivo. Ann Neurol 2000;47:381–384