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

Annals of Neurology - Tập 34 Số 6 - Trang 827-834 - 1993
Filippo M. Santorelli1, Sara Shanske2, Alfons Macaya3, Darryl C. DeVivo3, S. DiMauro2
1H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia-Presbyterian Medical Center, New York, NY.
2H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, New York, NY
3Division of Pediatric Neurology, Columbia‐Presbyterian Medical Center, New York, NY

Tóm tắt

AbstractTwelve 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.

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Annals of Neurology

Tập 34 Số 6

827-834

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