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

PURPOSE: 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 associ...

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Autores principales: Nochez, Yannick, Arsene, Sophie, Gueguen, Naig, Chevrollier, Arnaud, Ferré, Marc, Guillet, Virginie, Desquiret, Valérie, Toutain, Annick, Bonneau, Dominique, Procaccio, Vincent, Amati-Bonneau, Patrizia, Pisella, Pierre-Jean, Reynier, Pascal
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661005/
https://www.ncbi.nlm.nih.gov/pubmed/19325939
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author Nochez, Yannick
Arsene, Sophie
Gueguen, Naig
Chevrollier, Arnaud
Ferré, Marc
Guillet, Virginie
Desquiret, Valérie
Toutain, Annick
Bonneau, Dominique
Procaccio, Vincent
Amati-Bonneau, Patrizia
Pisella, Pierre-Jean
Reynier, Pascal
author_facet Nochez, Yannick
Arsene, Sophie
Gueguen, Naig
Chevrollier, Arnaud
Ferré, Marc
Guillet, Virginie
Desquiret, Valérie
Toutain, Annick
Bonneau, Dominique
Procaccio, Vincent
Amati-Bonneau, Patrizia
Pisella, Pierre-Jean
Reynier, Pascal
author_sort Nochez, Yannick
collection PubMed
description PURPOSE: 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.
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spelling pubmed-26610052009-03-26 Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect Nochez, Yannick Arsene, Sophie Gueguen, Naig Chevrollier, Arnaud Ferré, Marc Guillet, Virginie Desquiret, Valérie Toutain, Annick Bonneau, Dominique Procaccio, Vincent Amati-Bonneau, Patrizia Pisella, Pierre-Jean Reynier, Pascal Mol Vis Research Article PURPOSE: 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. Molecular Vision 2009-03-27 /pmc/articles/PMC2661005/ /pubmed/19325939 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Nochez, Yannick
Arsene, Sophie
Gueguen, Naig
Chevrollier, Arnaud
Ferré, Marc
Guillet, Virginie
Desquiret, Valérie
Toutain, Annick
Bonneau, Dominique
Procaccio, Vincent
Amati-Bonneau, Patrizia
Pisella, Pierre-Jean
Reynier, Pascal
Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect
title Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect
title_full Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect
title_fullStr Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect
title_full_unstemmed Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect
title_short Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect
title_sort acute and late-onset optic atrophy due to a novel opa1 mutation leading to a mitochondrial coupling defect
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661005/
https://www.ncbi.nlm.nih.gov/pubmed/19325939
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