title: SURFEIT-1 gene analysis and two-dimensional blue native gel electrophoresis in cytochrome c oxidase deficiency.
abstract: Leigh syndrome, a progressive, often fatal, neurodegenerative disorder, is frequently associated with a deficiency in the activity of cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain. In contrast to NADH:ubiquinone oxidoreductase and succinate dehydrogenase deficiencies, no mutations in nuclear genes encoding COX subunits have been identified thus far. Very recently, however, a Leigh syndrome complementation group has been identified which showed mutations in the SURFEIT-1 (SURF-1) gene. The results of a mutational detection study in 16 new randomly selected COX-deficient patients revealed a new mutation (C688T) in 2 patients and the earlier reported 845delCT mutation in 2 additional patients. In addition, we evaluated the diagnostic value of two-dimensional blue native gel electrophoresis. We show that this technique reveals distinct patterns of both fully and partially assembled COX complexes and is thereby capable of discrimination between COX-deficient SURF-1 and non-SURF-1-mutated patients.
authors.affiliation: Department of Paediatrics, Nijmegen Centre for Mitochondrial Disorders, University Hospital St. Radboud, Nijmegen, 6500 HB, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Coenen
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: L G
authors.initials: LG
authors.lastname: Nijtmans
authors.forename: E
authors.initials: E
authors.lastname: Morava
authors.forename: I
authors.initials: I
authors.lastname: Marquardt
authors.forename: H J
authors.initials: HJ
authors.lastname: Girschick
authors.forename: F J
authors.initials: FJ
authors.lastname: Trijbels
authors.forename: L A
authors.initials: LA
authors.lastname: Grivell
authors.forename: J A
authors.initials: JA
authors.lastname: Smeitink
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D030401:Cytochrome-c Oxidase Deficiency; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000302:isolation & purification; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017354:Point Mutation; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C092928:Surf-1 protein; D004247:DNA; D003576:Electron Transport Complex IV