Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency
- S Lebon1,
- M Chol1,
- P Benit1,
- C Mugnier1,
- D Chretien1,
- I Giurgea1,
- I Kern3,
- E Girardin3,
- L Hertz-Pannier2,
- P de Lonlay1,
- A Rötig1,
- P Rustin1,
- A Munnich1
- 1INSERM U393, Department of Genetics, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France
- 2Department of Pediatric Radiology, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France
- 3Department of Pediatrics, Hôpitaux Universitaires de Genève, rue Willy Donzé 6, 1211 Genève 14, Switzerland
- Correspondence to: Dr A Munnich INSERM U-323, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France; munnichnecker.fr
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.
