Homoplasmy of a mitochondrial 3697G>A mutation causes Leigh syndrome.

Herein we report on three siblings with Leigh syndrome (LS) harboring a homoplasmic m.3697G>A mutation (G131S) in the MT-ND1 gene. The siblings' phenotypically normal mother had the same, albeit heteroplasmic, mutation. Complex I deficiency (8% of average control values) was demonstrated in a biceps brachii muscle from one of the patients. Heteroplasmic m.3697G>A has been reported in patients with Leber's hereditary optic neuropathy, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes and Stüve-Wiedemann syndrome. Because all three patients in this series carried m.3697G>A in a homoplasmic manner and had LS, we suggest that homoplasmy of m.3697G>A may cause the LS phenotype.