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 subunit II of cytochrome c oxidase (COX) in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heretoplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-positive fibers; it was not found in blood samples from the patient's asymptomatic maternal relatives. Immunoblot analysis showed a reduced concentration of both COX II and COX I polypeptides, suggesting impaired assembly of COX holoenzyme.Funded by: Fondo de Investigación Sanitaria (FIS). Grant Number: 00/0370; Ministerio de Sanidad, Spain; Dirección General de Investigación, Comunidad de Madrid. Grant Number: 08.5/0013/2000; Sigma-Tau; F.I.S.; Asociación Española para el Estudio de la Esclerosis Lateral Amiotrófica (ADELA) and ISC III. Grant Number: 98/3166.Peer Reviewe