Analysis of the mitochondrial encoded subunits of complex 1 in 20 patients with a complex 1 deficiency

NADH-ubiquinone oxidoreductase or complex 1 deficiency is a frequently diagnosed enzyme defect of the oxidative phosphorylation (OXPHOS) system in humans. However, in many patients, with complex 1 deficiency and clinical symptoms suggestive of mitochondrial disease, often no genetic defect can be found after investigation of the most common mitochondrial DNA (mtDNA) mutations. In this study, 20 patients were selected with a biochemically documented complex 1 defect and no common mtDNA mutation. We used the Denaturing Gradient Get Electrophoresis (DGGE) method with primers encompassing all mitochondrial encoded fragments, to search in a systematic manner for mutations in the mitochondrial genome of complex 1. In our group of patients, we we re able to detect a total of 96 nucleotide changes. We were not able to find any disease causing mutation in the mitochondrial encoded subunits of complex 1. These results suggested that the complex 1 deficiency in this group of patients is most probably caused by a defect in one of the nuclear encoded structural genes of complex 1, or in one of the genes involved in proper assembly of the enzyme. (C) 2004 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.