title: The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh's syndrome.
abstract: 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.
authors.affiliation: H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia-Presbyterian Medical Center, New York, NY.
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: A
authors.initials: A
authors.lastname: Macaya
authors.forename: D C
authors.initials: DC
authors.lastname: DeVivo
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007888:Leigh Disease / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation
chemical_list: D004272:DNA, Mitochondrial