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

• Published in: European journal of paediatric neurology 2004, Vol.8 (6), p.299-306
• Main Authors: Meulemans, Ann, Lissens, Willy, Coster, Rudy Van, Meirleir, Linda De, Smet, Joél, Nassogne, Marie-Cécile, Liebaers, Inge, Seneca, Sara
• Format: Article
• Language: English
• Subjects: Age of Onset; Child; Child, Preschool; Coloring Agents; Complex I; DGGE; DNA, Mitochondrial - genetics; Electron Transport Complex I - deficiency; Electron Transport Complex I - genetics; Electrophoresis, Gel, Pulsed-Field; Female; Heteroduplex Analysis; Humans; Infant; Infant, Newborn; Male; Mitochondrial DNA; Mitochondrial Encephalomyopathies - genetics; Mutation; Nucleic Acid Denaturation; Pathogenesis; Polymorphism; Polymorphism, Genetic - genetics; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 1090-3798; 1532-2130
• DOI: 10.1016/j.ejpn.2004.07.006

NADH-ubiquinone oxidoreductase or complex I deficiency is a frequently diagnosed enzyme defect of the oxidative phosphorylation (OXPHOS) system in humans. However, in many patients, with complex I 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 I defect and no common mtDNA mutation. We used the Denaturing Gradient Gel Electrophoresis (DGGE) method with primers encompassing all mitochondrial encoded fragments, to search in a systematic manner for mutations in the mitochondrial genome of complex I. In our group of patients, we were 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 I. These results suggested that the complex I deficiency in this group of patients is most probably caused by a defect in one of the nuclear encoded structural genes of complex I, or in one of the genes involved in proper assembly of the enzyme.