The Mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh's syndrome

Filippo M. Santorelli, Sara Shanske, Alfons Macaya, Darryl C. DeVivo, Salvatore DiMauro

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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 not found in >200 patients with other 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 nt 8993 mutation is a relatively common cause of Leigh's syndrome.

Original languageEnglish
Pages (from-to)827-834
Number of pages8
JournalAnnals of Neurology
Issue number6
Publication statusPublished - Dec 1993

ASJC Scopus subject areas

  • Neuroscience(all)


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