A new mtDNA mutation in the tRNA(Lys) gene associated with myoclonic epilepsy and ragged-red fibers (MERRF)

Myoclonic epilepsy with ragged-red fibers (MERRF) has been associated with an A→G transition at mtDNA nt 8344, within a conserved region of the tRNA(Lys) gene. Although the 8344 mutation is highly prevalent in patients with MERRF, it is not observed in 10%-20% of the cases, suggesting genetic heterogeneity. We have sequenced the tRNA(Lys) gene of five MERRF patients lacking the common 8344 mutation. One of these showed a novel T→C transition at nucleotide position 8356, disrupting a highly conserved base pair in the TΨC stem. The mutant mtDNA population was essentially homoplasmic in muscle but was heteroplasmic in blood (47%). Neither 20 patients with other mitochondrial diseases nor 25 controls carried this mutation. These findings suggest that tRNA(Lys) alterations may play a specific role in the pathogenesis of MERRF syndrome.