Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA - PubMed (original) (raw)
. 1999 Sep 30;341(14):1037-44.
doi: 10.1056/NEJM199909303411404.
M G Hanna, H Reichmann, C Bruno, A S Penn, K Tanji, F Pallotti, S Iwata, E Bonilla, B Lach, J Morgan-Hughes, S DiMauro
Affiliations
- PMID: 10502593
- DOI: 10.1056/NEJM199909303411404
Free article
Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA
A L Andreu et al. N Engl J Med. 1999.
Free article
Abstract
Background: The mitochondrial myopathies typically affect many organ systems and are associated with mutations in mitochondrial DNA (mtDNA) that are maternally inherited. However, there is also a sporadic form of mitochondrial myopathy in which exercise intolerance is the predominant symptom. We studied the biochemical and molecular characteristics of this sporadic myopathy.
Methods: We sequenced the mtDNA cytochrome b gene in blood and muscle specimens from five patients with severe exercise intolerance, lactic acidosis in the resting state (in four patients), and biochemical evidence of complex III deficiency. We compared the clinical and molecular features of these patients with those previously described in four other patients with mutations in the cytochrome b gene.
Results: We found a total of three different nonsense mutations (G15084A, G15168A, and G15723A), one missense mutation (G14846A), and a 24-bp deletion (from nucleotide 15498 to 15521) in the cytochrome b gene in the five patients. Each of these mutations impairs the enzymatic function of the cytochrome b protein. In these patients and those previously described, the clinical manifestations included progressive exercise intolerance, proximal limb weakness, and in some cases, attacks of myoglobinuria. There was no maternal inheritance and there were no mutations in tissues other than muscle. The absence of these findings suggests that the disorder is due to somatic mutations in myogenic stem cells after germ-layer differentiation. All the point mutations involved the substitution of adenine for guanine, but all were in different locations.
Conclusions: The sporadic form of mitochondrial myopathy is associated with somatic mutations in the cytochrome b gene of mtDNA. This myopathy is one cause of the common and often elusive syndrome of exercise intolerance.
Comment in
- Muscle pain, fatigue, and mitochondriopathies.
Griggs RC, Karpati G. Griggs RC, et al. N Engl J Med. 1999 Sep 30;341(14):1077-8. doi: 10.1056/NEJM199909303411411. N Engl J Med. 1999. PMID: 10502600 No abstract available. - Mitochondrial disease in patients with exercise intolerance.
Vladutiu GD, Tabone E. Vladutiu GD, et al. N Engl J Med. 2000 Feb 10;342(6):438-9; author reply 439-40. doi: 10.1056/NEJM200002103420616. N Engl J Med. 2000. PMID: 10681226 No abstract available. - Mitochondrial disease in patients with exercise intolerance.
MirĂ³ O, Grav JM, Casademont J. MirĂ³ O, et al. N Engl J Med. 2000 Feb 10;342(6):439; author reply 439-40. N Engl J Med. 2000. PMID: 10681227 No abstract available.
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