Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect - Université d'Angers Accéder directement au contenu
Article Dans Une Revue Molecular Vision Année : 2009

Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect

Yannick Nochez
  • Fonction : Auteur
Sophie Arsene
  • Fonction : Auteur
Marc Ferré
Virginie Guillet
  • Fonction : Auteur
Annick Toutain
Dominique Bonneau
  • Fonction : Auteur
  • PersonId : 992770
Vincent Procaccio
  • Fonction : Auteur
  • PersonId : 991978
Pierre-Jean Pisella
  • Fonction : Auteur
Pascal Reynier
  • Fonction : Auteur
  • PersonId : 991986

Résumé

PurposeAutosomal dominant optic atrophy (ADOA, OMIM 165500), an inherited optic neuropathy that leads to retinal ganglion cell degeneration and reduced visual acuity during the early decades of life, is mainly associated with mutations in the OPA1 gene. Here we report a novel ADOA phenotype associated with a new pathogenic OPA1 gene mutation. Methods The patient, a 62-year-old woman, was referred for acute, painless, and severe visual loss in her right eye. Acute visual loss in her left eye occurred a year after initial presentation. MRI confirmed the diagnosis of isolated atrophic bilateral optic neuropathy. We performed DNA sequencing of the entire coding sequence and the exon/intron junctions of the OPA1 gene, and we searched for the mitochondrial DNA mutations responsible for Leber hereditary optic atrophy by sequencing entirely mitochondrial DNA. Mitochondrial respiratory chain complex activity and mitochondrial morphology were investigated in skin fibroblasts from the patient and controls. Results We identified a novel heterozygous missense mutation (c.2794C>T) in exon 27 of the OPA1 gene, resulting in an amino acid change (p.R932C) in the protein. This mutation, which affects a highly conserved amino acids, has not been previously reported, and was absent in 400 control chromosomes. Mitochondrial DNA sequence analysis did not reveal any mutation associated with Leber hereditary optic neuropathy or any pathogenic mutations. The investigation of skin fibroblasts from the patient revealed a coupling defect of oxidative phosphorylation and a larger proportion of short mitochondria than in controls. Conclusions The presence of an OPA1 mutation indicates that this sporadic, late-onset acute case of optic neuropathy is related to ADOA and to a mitochondrial energetic defect. This suggests that the mutational screening of the OPA1 gene would be justified in atypical cases of optic nerve atrophy with no evident cause.

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Dates et versions

hal-03406919 , version 1 (28-10-2021)

Identifiants

  • HAL Id : hal-03406919 , version 1
  • OKINA : ua326

Citer

Yannick Nochez, Sophie Arsene, Naïg Gueguen, Arnaud Chevrollier, Marc Ferré, et al.. Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect. Molecular Vision, 2009, 15, pp.598 - 608. ⟨hal-03406919⟩

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