Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency.
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.
Lebon
S
S
INSERM U393, Department of Genetics, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
Chol
M
M
Benit
P
P
Mugnier
C
C
Chretien
D
D
Giurgea
I
I
Kern
I
I
Girardin
E
E
Hertz-Pannier
L
L
de Lonlay
P
P
Rötig
A
A
Rustin
P
P
Munnich
A
A
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
D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I