title: Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect.
abstract: OBJECTIVE
  Autosomal 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.
authors.affiliation: Centre Hospitalier Universitaire de Tours, Service d'Ophtalmologie, Tours, France. yannick.nochez@free.fr
authors.forename: Yannick
authors.initials: Y
authors.lastname: Nochez
authors.forename: Sophie
authors.initials: S
authors.lastname: Arsene
authors.forename: Naig
authors.initials: N
authors.lastname: Gueguen
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevrollier
authors.forename: Marc
authors.initials: M
authors.lastname: Ferré
authors.forename: Virginie
authors.initials: V
authors.lastname: Guillet
authors.forename: Valérie
authors.initials: V
authors.lastname: Desquiret
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amati-Bonneau
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Pisella
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier