Cited by 1,446Mitochondrial Function and PathologyHereditary Neurological DisordersGlaucoma and retinal disorders

Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy

Delettre, Cécile, Lenaers, Guy, Griffoin, Jean-Michel, Gigarel, Nadine, Lorenzo, Corinne, Belenguer, Pascale, Pelloquin, Laetitia, Grosgeorge, Josiane +8 more·2000·Nature Genetics

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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Crossref · 10.1038/79936

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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.
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
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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