Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy
Abstract
Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy occurring in 1 in 50,000 individuals that features progressive loss in visual acuity leading, in many cases, to legal blindness. Phenotypic variations and loss of retinal ganglion cells, as found in Leber hereditary optic neuropathy (LHON), have suggested possible mitochondrial impairment. The OPA1 gene has been localized to 3q28-q29 (refs 13-19). We describe here a nuclear gene, OPA1, that maps within the candidate region and encodes a dynamin-related protein localized to mitochondria. We found four different OPA1 mutations, including frameshift and missense mutations, to segregate with the disease, demonstrating a role for mitochondria in retinal ganglion cell pathophysiology.
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Loss-of-function mutations in MFN2 and OPA1 genes cause Charcot-Marie-Tooth type 2A (CMT2A) and dominant optic atrophy (DOA), respectively.
“Loss-of-function mutations in MFN2 and OPA1 genes cause two neurodegenerative diseases, Charcot–Marie–Tooth type 2A (CMT2A) [179] and dominant optic atrophy (DOA) [180, 181], respectively.”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [181]
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Ahola, S., Langer, T., & MacVicar, T. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033936 · Cited by 37 · see citing works
Mitochondrial Function and Neurodegenerative Diseases
Wilkins, H. M., Weidling, I., Koppel, S., Wang, X., von Schulze, A., & Swerdlow, R. H. (2018) · The Molecular and Cellular Basis of Neurodegenerative Diseases · doi:10.1016/b978-0-12-811304-2.00013-4 · Cited by 2 · see citing works
- Authors
- Delettre, C., Lenaers, G., Griffoin, J.-M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., Astarie-Dequeker, C., Lasquellec, L., Arnaud, B., Ducommun, B., Kaplan, J., & Hamel, C. P.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Hôpital Necker-Enfants Malades (FR)
- Sanofi (France) (FR)
- Hôpital Gui de Chauliac (FR)
- Corresponding author
- Ducommun, Bernard
- Hamel, Christian P.
- ORCID
- Venue
- Nature Genetics
- Published
- 2000-10
- Volume
- 26
- Issue
- 2
- Pages
- 207-210
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2094113524
- Cited by
- 1,446
- References
- 31
- Citations by year
- 2026: 23 · 2025: 32 · 2024: 43 · 2023: 56 · 2022: 46 · 2021: 73 · 2020: 58 · 2019: 67 · 2018: 61 · 2017: 68 · 2016: 66 · 2015: 62 · 2014: 53 · 2013: 70 · 2012: 89
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- OPA1, autosomal dominant optic atrophy, dynamin-related proteins, optic neuropathy, retinal ganglion cells, mitochondrial dysfunction, gene mapping, frameshift mutation, missense mutations, autosomal dominant inheritance, Leber's hereditary optic neuropathy
- MeSH terms
- Amino Acid Sequence, Cell Nucleus, Chromosome Mapping, Chromosomes, Human, Pair 3, Exons, Female, Genes, Dominant, Humans, Male, Mitochondria, Molecular Sequence Data, Mutation, Optic Atrophy, Pedigree, Polymorphism, Genetic, Saccharomyces cerevisiae, Schizosaccharomyces, Sequence Alignment, Sequence Homology, Amino Acid, In Situ Hybridization, Fluorescence, GTP Phosphohydrolases, Dynamins
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