title: Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency.
abstract: Starting from a cohort of 50 NADH-oxidoreductase (complex I) deficient patients, we carried out the systematic sequence analysis of all mitochondrially encoded complex I subunits (ND1 to ND6 and ND4L) in affected tissues. This approach yielded the unexpectedly high rate of 20% mutation identification in our series. Recurrent heteroplasmic mutations included two hitherto unreported (T10158C and T14487C) and three previously reported mutations (T10191C, T12706C and A13514G) in children with Leigh or Leigh-like encephalopathy. The recurrent mutations consistently involved T-->C transitions (p<10(-4)). This study supports the view that an efficient molecular screening should be based on an accurate identification of respiratory chain enzyme deficiency.
authors.affiliation: INSERM U393, Department of Genetics, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Lebon
authors.forename: M
authors.initials: M
authors.lastname: Chol
authors.forename: P
authors.initials: P
authors.lastname: Benit
authors.forename: C
authors.initials: C
authors.lastname: Mugnier
authors.forename: D
authors.initials: D
authors.lastname: Chretien
authors.forename: I
authors.initials: I
authors.lastname: Giurgea
authors.forename: I
authors.initials: I
authors.lastname: Kern
authors.forename: E
authors.initials: E
authors.lastname: Girardin
authors.forename: L
authors.initials: L
authors.lastname: Hertz-Pannier
authors.forename: P
authors.initials: P
authors.lastname: de Lonlay
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: A
authors.initials: A
authors.lastname: Munnich
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics; D008297:Male; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I