THE A-TRANSITION TO G-TRANSITION AT NT-3243 OF THE MITOCHONDRIAL TRNA(LEU)(UUR) MAY CAUSE AN MERRF SYNDROME

Objective-To verify the phenotype to genotype correlations of mitochon drial DNA (mtDNA) related disorders in an atypical maternally inherite d encephalomyopathy. Methods-Neuroradiological, morphological, biochem ical, and molecular genetic analyses were performed on the affected me mbers of a pedigree harbouring the heteroplasmic A to nucleotide 3243 of tRNA(Leu(UUR)), which is usually associated with the syndrome of mi tochondrial encephalomyopathy, lactic acidosis, and stroke-like episod es (MELAS). Results-The proband was affected by a fullblown syndrome o f myoclonic epilepsy with red fibres (MERRF), severe atrophy, and basa l ganglia calcifications, without the MRI T2 hyperintense focal lesion s which are pathognomonic of MELAS. Oligosymptomatic relatives were va riably affected by lipomas, goitre, brain atrophy, and basal ganglia c alcifications. Muscle biopsies in the proband and his mother showed a MELAS-like pattern with cytochrome c oxidase hyperreactive ragged red fibres and strongly succinate dehydrogenase reactive vessels. Quantifi cation of the A3243G mutation disclosed 78% and 70% of mutated mtDNA i n the muscle of the severely affected proband and of his oligosymptoma tic mother respectively. Nucleotide sequencing of the mitochondrial tR NA(Leu(UUR)) and tRNA(Lys) in the proband's muscle failed to show any additional nucleotide change which could account for the clinical oddi ty of this pedigree by modulating the expression of the primary pathog enic mutation. Conclusion-So far, MERRF has been associated with mutat ions of the mitochondrial tRNA(Lys), and MELAS with mutations of the m itochondrial tRNA(Leu(UUR)). NOW MERRF may also be considered among th e clinical syndromes associated with the A to G transition at nt 3243 of the tRNA(Leu(UUR)).