Analysis of the mitochondrial encoded subunits of complex I in 20 patients with a complex I deficiency.
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.
Meulemans
Ann
A
Center for Medical genetics, Dutch speaking Free University of Brussels, AZ-VUB, Laarbeeklaan 101, B-1090 Brussels, Belgium.
Lissens
Willy
W
Van Coster
Rudy
R
De Meirleir
Linda
L
Smet
Joél
J
Nassogne
Marie-Cécile
MC
Liebaers
Inge
I
Seneca
Sara
S
D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004396:Coloring Agents; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics*; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D020180:Heteroduplex Analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D009154:Mutation; D009691:Nucleic Acid Denaturation; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004396:Coloring Agents; D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I