The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy 'plus' phenotype - Université d'Angers Accéder directement au contenu
Article Dans Une Revue Brain - A Journal of Neurology Année : 2011

The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy 'plus' phenotype

C. Rouzier
  • Fonction : Auteur
Sylvie Bannwarth
  • Fonction : Auteur
A. Chaussenot
  • Fonction : Auteur
A. Verschueren
  • Fonction : Auteur
N. Bonello-Palot
  • Fonction : Auteur
K. Fragaki
  • Fonction : Auteur
A. Cano
  • Fonction : Auteur
Jean Pouget
  • Fonction : Auteur
J. Pellissier
  • Fonction : Auteur
Vincent Procaccio
  • Fonction : Auteur
  • PersonId : 991978
Brigitte Chabrol
  • Fonction : Auteur
Veronique Paquis-Flucklinger
  • Fonction : Auteur

Résumé

MFN2 and OPA1 genes encode two dynamin-like GTPase proteins involved in the fusion of the mitochondrial membrane. They have been associated with Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy, respectively. We report a large family with optic atrophy beginning in early childhood, associated with axonal neuropathy and mitochondrial myopathy in adult life. The clinical presentation looks like the autosomal dominant optic atrophy 'plus' phenotype linked to OPA1 mutations but is associated with a novel MFN2 missense mutation (c.629A>T, p.D210V). Multiple mitochondrial DNA deletions were found in skeletal muscle and this observation makes MFN2 a novel gene associated with 'mitochondrial DNA breakage' syndrome. Contrary to previous studies in patients with Charcot-Marie-Tooth disease type 2A, fibroblasts carrying the MFN2 mutation present with a respiratory chain deficiency, a fragmentation of the mitochondrial network and a significant reduction of MFN2 protein expression. Furthermore, we show for the first time that impaired mitochondrial fusion is responsible for a deficiency to repair stress-induced mitochondrial DNA damage. It is likely that defect in mitochondrial DNA repair is due to variability in repair protein content across the mitochondrial population and is at least partially responsible for mitochondrial DNA instability.

Dates et versions

hal-03408506 , version 1 (29-10-2021)

Identifiants

Citer

C. Rouzier, Sylvie Bannwarth, A. Chaussenot, Arnaud Chevrollier, A. Verschueren, et al.. The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy 'plus' phenotype. Brain - A Journal of Neurology , 2011, 135 (Pt 1), pp.23 - 34. ⟨10.1093/brain/awr323⟩. ⟨hal-03408506⟩

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