THE MUTATION AT NT-8993 OF MITOCHONDRIAL-DNA IS A COMMON-CAUSE OF LEIGHS SYNDROME

Twelve patients with Leigh's syndrome from 10 families harbored a T > G point mutation at nt 8993 of mtDNA. This mutation, initially associa ted with neurogenic weakness, ataxia, and retinitis pigmentosa, was la ter found to result in the Leigh phenotype when present in a high perc entage. In our patients,the mutation was heteroplasmic, maternally inh erited, and appeared to segregate rapidly within the pedigrees. Quanti tative analysis revealed a good correlation between percentage of muta nt mitochondrial genomes and severity of the clinical phenotype. The m utation was not found in >200 patients with other mitochondrial enceph alomyopathies or in controls. Mitochondrial enzyme activities were nor mal in all but 1 patient, and there were no ragged-red fibers in the m uscle biopsy. Lactic acidosis was present in 92% of patients. Our find ings suggest that the mtDNA nt 8993 mutation is a relatively common ca use of Leigh's syndrome.