2 NOVEL PATHOGENIC MITOCHONDRIAL-DNA MUTATIONS AFFECTING ORGANELLE NUMBER AND PROTEIN-SYNTHESIS - IS THE TRANSFER RNA(LEU(UUR)) GENE AN ETIOLOGIC HOT-SPOT
Ct. Moraes et al., 2 NOVEL PATHOGENIC MITOCHONDRIAL-DNA MUTATIONS AFFECTING ORGANELLE NUMBER AND PROTEIN-SYNTHESIS - IS THE TRANSFER RNA(LEU(UUR)) GENE AN ETIOLOGIC HOT-SPOT, The Journal of clinical investigation, 92(6), 1993, pp. 2906-2915
We identified two patients with pathogenic single nucleotide changes i
n two different mitochondrial tRNA genes: the first mutation in the tR
NA(Asn). gene, and the ninth known mutation in the tRNA(Leu(UUR)) gene
. The mutation in tRNA(Asn) was associated with isolated ophthalmopleg
ia, whereas the mutation in tRNA(Leu(UUR)) caused a neurological syndr
ome resembling MERRF (myoclonus epilepsy and ragged-red fibers) plus o
ptic neuropathy, retinopathy, and diabetes. Both mutations were hetero
plasmic, with higher percentages of mutant mtDNA in affected tissues,
and undetectable levels in maternal relatives. Analysis of single musc
le fibers indicated that morphological and biochemical alterations app
eared only when the proportions of mutant mtDNA exceeded 90% of the to
tal cellular mtDNA pool. The high incidence of mutations in the tRNA(L
eu(UUR)) gene suggests that this region is an ''etiologic hot spot'' i
n mitochondrial disease.