G8363A mutation in the mitochondrial DNA transfer ribonucleic acidLys gene: another cause of Leigh syndrome.

We identified a G-->A transition at nt-8363 in the mitochondrial DNA transfer ribonucleic acidLys gene in blood and muscle from a 13-month-old girl who had clinical and neuroradiologic evidence of Leigh syndrome and died at age 27 months. The mutation was less abundant in the same tissues from the patient's mother, who developed myoclonus epilepsy with ragged red fibers (MERRF) in her late 20s. In both mother and daughter, muscle histochemistry showed ragged red and cytochrome c oxidase-negative fibers and biochemical analysis showed partial defects of multiple respiratory-chain enzymes. A maternal half-sister of the proband had died at 2.5 years of age from neuropathologically proven Leigh syndrome. The G8363A mutation, which previously had been associated with cardiomyopathy and hearing loss, MERRF, and multiple lipomas, also should be included in the differential diagnosis of maternally inherited Leigh syndrome.