MITOCHONDRIAL ENCEPHALOMYOPATHY ASSOCIATED WITH A SINGLE NUCLEOTIDE PAIR DELETION IN THE MITOCHONDRIAL TRNA(LEU(UUR)) GENE

The investigation of pathogenic mitochondrial DNA (mtDNA) mutations ha s revealed a complex relation between patient genotype and phenotype. For unknown reasons, some mtDNA mutations produce specific clinical ma nifestations such as chronic progressive external ophthalmoplegia; myo clonic epilepsy and ragged-red fiber disease (MERRF); and mitochondria l encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) . To enhance our understanding of the association between genotype and phenotype, we investigated a patient with mitochondrial encephalomyop athy and severe cerebral calcifications for a mtDNA mutation. There wa s a deletion of one of three T:A nucleotide pairs in the tRNA(Leu(UUR) ) gene of the mtDNA involving positions 3271 to 3273. Pedigree analysi s suggested that this mutation may have occurred spontaneously in the proband. This analysis represents the smallest mtDNA deletion observed to date and is the first deletion identified within a mitochondrial t RNA. This observation emphasizes the importance of delineating the pre cise mutation responsible for an oxidative phosphorylation disease for patient diagnosis as well as for genetic counseling of maternal linea ge relatives.