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Twelve patients with Leigh's syndrome from 10 families harbored a T>G point mutation at nt 8993 of mtDNA.This mutation,initially associated with neurogenic weakness,ataxia and retinitis pigmentosa,was later found to result in the Leigh phenotype when present in a high percentage.In our patients,the mutation was heteroplasmic,maternally inherited,and appeared to segregate rapidly within the pedigrees.Quantitative analysis revealed a good correlation between percentage of mutant mitochondrial genomes and severity of the clinical phenotype.The mutation was found in>200 patients with older mitochondrial encephalomyopathies or in controls.Mitochondrial enzyme activities were normal in all but 1 patient,and there were no ragged-red fibers in the muscle biopsy.Lactic acidosis was present in 92% of patients.Our findings suggest that the mtDNA nt8993 mutation is a relatively common cause of Leigh's syndrome. |
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