Zeviani M, Gellera C, Antozzi C, Rimoldi M, Morandi L, Villani F, Tiranti V, DiDonato S
Istituto Nazionale Neurologico C Besta, Milan, Italy.
Lancet. 1991 Jul 20;338(8760):143-7. doi: 10.1016/0140-6736(91)90136-d.
Different point mutations of the mitochondrial genome, which all affect the ability of mitochondria to translate their own genes and lead to partial defects of mtDNA-dependent respiratory complexes, are related to distinct clinical mitochondrial disorders. A new maternally inherited disorder, characterised by a combination of adult-onset myopathy and cardiomyopathy, with no clinical involvement of the nervous system, was found in members of a single large pedigree. A heteroplasmic new mutation was identified in the mtDNA gene specifying tRNA(Leu)(UUR). This mutation segregated specifically with the disorder, and there were significant correlations between the proportion of the mtDNA that was of the mutant form and the activities (normalised for citrate synthase activity) of the two mtDNA-dependent respiratory enzymes (complex I, r = -0.71, p less than 0.005: complex IV r = -0.77, p less than 0.005) and the maximum oxygen consumption (r = -0.82, p less than 0.005), a physiological index of aerobic metabolism. These findings strongly suggest that the tRNA(Leu)(UUR) mutation is the genetic cause of this disorder, and that lesions of mtDNA should be considered in the differential diagnosis of the hereditary cardiomyopathies.
