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

TLDR

A T>G point mutation at mtDNA position 8993, previously linked to neurogenic weakness, ataxia, and retinitis pigmentosa, is now recognized as a frequent cause of Leigh syndrome in patients from 10 families. In these patients the mutation was heteroplasmic, maternally inherited, rapidly segregated, correlated with disease severity, absent in over 200 other mitochondrial disorders, and associated with lactic acidosis in 92%, indicating it is a common cause of Leigh syndrome.

Abstract

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.