Difference between revisions of "Nochez 2009 Mol Vis"
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|authors=Nochez Y, Arsene S, Gueguen N, Chevrollier A, Ferre M, Guillet V, Desquiret V, Toutain A, Bonneau D, Procaccio V, Amati-Bonneau P, Pisella PJ, Reynier P | |authors=Nochez Y, Arsene S, Gueguen N, Chevrollier A, Ferre M, Guillet V, Desquiret V, Toutain A, Bonneau D, Procaccio V, Amati-Bonneau P, Pisella PJ, Reynier P | ||
|year=2009 | |year=2009 | ||
|journal= | |journal=Mol. Vis. | ||
|abstract=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. | |abstract=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. | ||
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|topics=Respiration; OXPHOS; ETS Capacity, Coupling; Membrane Potential | |topics=Respiration; OXPHOS; ETS Capacity, Coupling; Membrane Potential | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Revision as of 10:47, 14 October 2010
| Nochez Y, Arsene S, Gueguen N, Chevrollier A, Ferré M, Guillet V, Desquiret V, Toutain A, Bonneau D, Procaccio V, Amati-Bonneau P, Pisella PJ, Reynier P (2009) Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect. Mol. Vis. 15: 598-608. |
Nochez Y, Arsene S, Gueguen N, Chevrollier A, Ferre M, Guillet V, Desquiret V, Toutain A, Bonneau D, Procaccio V, Amati-Bonneau P, Pisella PJ, Reynier P (2009) Mol. Vis.
Abstract: 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.
Labels:
Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Human Tissue;cell: Neurons; Brain"Neurons; Brain" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Enzyme: Uncoupler Protein"Uncoupler Protein" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Coupling; Membrane Potential"Coupling; Membrane Potential" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k
