title: Analysis of mitochondrial DNA sequences in patients with isolated or combined oxidative phosphorylation system deficiency.
abstract: BACKGROUND
  Enzyme deficiencies of the oxidative phosphorylation (OXPHOS) system may be caused by mutations in the mitochondrial DNA (mtDNA) or in the nuclear DNA.
  
  
  OBJECTIVE
  To analyse the sequences of the mtDNA coding region in 25 patients with OXPHOS system deficiency to identify the underlying genetic defect.
  
  
  RESULTS
  Three novel non-synonymous substitutions in protein-coding genes, 4681T-->C in MT-ND2, 9891T-->C in MT-CO3 and 14122A-->G in MT-ND5, and one novel substitution in the 12S rRNA gene, 686A-->G, were found. The definitely pathogenic mutation 3460G-->A was identified in an 18-year-old woman who had severe isolated complex I deficiency and progressive myopathy.
  
  
  CONCLUSIONS
  Bioinformatic analyses suggest a pathogenic role for the novel 4681T-->C substitution found in a boy with Leigh's disease. These results show that the clinical phenotype caused by the primary Leber's hereditary optic neuropathy mutation 3460G-->A is more variable than has been thought. In the remaining 23 patients, the role of mtDNA mutations as a cause of the OXPHOS system deficiency could be excluded. The deficiency in these children probably originates from mutations in the nuclear genes coding for respiratory enzyme subunits or assembly factors.
authors.forename: R
authors.initials: R
authors.lastname: Hinttala
authors.forename: R
authors.initials: R
authors.lastname: Smeets
authors.forename: J S
authors.initials: JS
authors.lastname: Moilanen
authors.forename: C
authors.initials: C
authors.lastname: Ugalde
authors.forename: J
authors.initials: J
authors.lastname: Uusimaa
authors.forename: J A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: K
authors.initials: K
authors.lastname: Majamaa
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000737:chemistry*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics*; D010802:Phylogeny
chemical_list: D004272:DNA, Mitochondrial