A novel heteroplasmic point mutation in the mitochondrial tRNA(Lys) gene in a sporadic case of mitochondrial encepharomyopathy: De novo mutation and no transmission to the offspring

We have identified a new mutation in the tRNA(Lys) gene of mtDNA, in a 49-y ear-old patient with mitochondrial encephalomyopathy. The mutation is a het eroplasmic G-->A transition at position 8328, which affects the anticodon s tem loop at a conserved site, The mutation was neither found in 100 control s nor in the maternal relatives of the patient. The level of mutated mtDNA was 57% in muscle, 13% in fibroblasts, and 10% in lymphocytes. Histochemist ry of muscle tissue revealed cytochrome c oxidase-deficient fibers with abn ormal accumulation of mitochondria. Biochemistry of muscle mitochondria sho wed slight cytochrome c oxidase deficiency. The mean ratio of mutant mtDNA to normal mtDNA in cytochrome c oxidase-positive muscle fibers was 59%, whe reas a mean ratio of 95% was found in cytochrome c oxidase-negative fibers. The difference between cytochrome c oxidase-positive and cytochrome c oxid ase-negative fibers was highly significant (P < 0.001). The mutation was no t found in muscle or lymphocytes of the mother and daughter of the proband, This is the first report of a de novo point mutation in the tRNA(Lys) gene in an individual expressing disease and the first report of lack of transm ission of the mutation to the offspring of a patient expressing a mitochond rial encephalomyopathy caused by a point mutation in mtDNA. Hum Mutat 13:20 3-209, 1999. (C) 1999 Wiley-Liss, Inc.