Intracellular Mitochondrial Triplasmy in a Patient with Two Heteroplasmic Base Changes

We report the clinical, biochemical, and genetic investigation of a patient with a severe mitochondrial encepha-lomyopathy. Genetic studies identified a novel, hetero-plasmic tRNA mutation at nt 10010. This T-←C transition is located in the DHU loop of mitochondrial tRNA Gly. In skeletal muscle, it was present at lower levels in cytochrome c oxidase (COX)-normal (87.2% ± 11%) compared with COX-deficient fibers (97.3% ± 2.6%); it was found in skin fibroblasts and blood cells, but at lower levels of heteroplasmy (15% ± 6% and 17% ± 10%, respectively). A second, heteroplasmic transition (A-←G), at nt 5656, showed a different distribution than the tRNA Gly mutation, with very low levels in skeletal muscle (