Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome c oxidase II gene

We report the first nonsense mutation (G7896A) in the mtDNA gene for subuni t Il of cytochrome c oxidase (COX in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in mu scle, blood, and fibroblasts from the patient and abundantly present in COX -deficient fibers, but less abundant in COX-positive fibers; it was not fou nd in blood samples from the patient's asymptomatic maternal relatives. Imm unoblot analysis showed a reduced concentration of both COX II and COX I po lypeptides, suggesting impaired assembly of COX holoenzyme.