Mitochondrial encephalomyopathy associated with a novel mutation in the mitochondrial tRNA(leu(UUR)) gene (A3243T)

We report a new mutation, an A-->T transition at nt 3243 in the mitochondrial tRNA(leu(UUR)) gene, in a 9-year-old girl who presented with muscle weakness of 3 years duration complicated by rapidly progressive encephalopathy, In muscle, the activity of the mitochondrial respiratory chain complexes I, III, and IV was markedly reduced, The mutation, involving a highly conserved base pair in the dihydrouridine loop, was heteroplasmic in muscle (81.4%), skin (69.3%), and blood (13.8%) and was not present in blood of 50 healthy individuals, The mitochondrial 3243 base is a ''hot spot'' for mutations; an A-->G transition at this position is found in a high proportion in most MELAS patients, Since the A-->T transtion creates a new recognition site for the restriction enzyme TspRI, both ApaI and TspRI should be used to exclude a mutation at nt 3243. (C) 1997 Academic Press.