SURFEIT-1 gene analysis and two-dimensional blue native gel electrophoresis in cytochrome c oxidase deficiency

Leigh syndrome, a progressive, often fatal, neurodegenerative disorder, is frequently associated with a deficiency in the activity of cytochrome c oxi dase (COX), the last enzyme of the mitochondrial respiratory chain. In cont rast to NADH:ubiquinone oxidoreductase and succinate dehydrogenase deficien cies, no mutations in nuclear genes encoding COX subunits have been identif ied thus far. Very recently, however, a Leigh syndrome complementation grou p 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 C OX-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 electr ophoresis. We show that this technique reveals distinct patterns of both fu lly and partially assembled COX complexes and is thereby capable of discrim ination between COX-deficient SURF-1 and non-SURF-1-mutated patients, (C) 1 999 Academic Press.