ArticleAnnals of neurology2015
Syndromic parkinsonism and dementia associated with OPA1 missense mutations.
Article in Annals of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.
- Gene expression meta-analysis of Parkinson's disease and its relationship with Alzheimer's disease.Molecular brain · 2019Pooled it
- The role of SUMOylation in regulating proteins that drive neuronal disease progression.Biochemistry and biophysics reports · 2026Review
- Rethinking Mitochondrial Parkinson's Disease in the α-Synuclein Seed Amplification Assays Era.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.Biomolecules · 2026Review
- Impact of Inner Retinal Layer Thinning on Visual Function in OPA1 Autosomal Dominant Optic Atrophy and Associations With Age and Genetic Variant Class.Investigative ophthalmology & visual science · 2026Article
- Disrupted energy metabolism is associated with retinal ganglion cell degeneration in autosomal dominant optic atrophy.Science advances · 2026Article
- OPA1 Deficiency Impairs NGF Signaling and Drives Sympathetic Neurodegeneration.JACC. Basic to translational science · 2026Article
- Whole-exome sequencing and burden analysis identify six novel candidate risk genes and expand the genetic landscape of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Case of autosomal dominant optic atrophy with relatively good visual function.BMC ophthalmology · 2025Article
- Deficits in mitochondrial dynamics and iron balance result in templated insertions.Nature communications · 2025Article
- Lysine acetylation modulates s-OPA1 GTPase activity and oligomerization in mitochondrial membrane remodeling.Protein science : a publication of the Protein Society · 2025Article
- The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease.Biomolecules · 2025Review
- Mitochondrial Dynamics in Blood Cancer Development and Progression.Current pharmacology reports · 2025Review
- Article
- Mitochondrial Parkinsonism: A Practical Guide to Genes and Clinical Diagnosis.Movement disorders clinical practice · 2024Review
- Targeting DRP1 with Mdivi-1 to correct mitochondrial abnormalities in ADOA+ syndrome.JCI insight · 2024Article
- Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice.Journal of biomedical science · 2024Article
- Dystonia, spastic tetraplegia, and ataxia due to a novel mutation in the dynamin domain of OPA1.Annals of clinical and translational neurology · 2024Article
- The human OPA1Cellular and molecular life sciences : CMLS · 2024Article
- Mitochondrial Chronic Progressive External Ophthalmoplegia.Brain sciences · 2024Review
45 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 7 institutions in 2 countries.
Funding
Abstract
objectiveMounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer disease with mitochondrial dysfunction, and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in postmitotic tissues. Here, we report 2 Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia.
methodsPatients were extensively studied by optical coherence tomography (OCT) to assess retinal nerve fibers, and underwent muscle and brain magnetic resonance spectroscopy (MRS), and muscle biopsy and fibroblasts were analyzed. Candidate genes were sequenced, and mtDNA was analyzed for rearrangements.
resultsAffected individuals displayed a slowly progressive syndrome characterized by CPEO, mitochondrial myopathy, sensorineural deafness, peripheral neuropathy, parkinsonism, and/or cognitive impairment, in most cases without visual complains, but with subclinical loss of retinal nerve fibers at OCT. Muscle biopsies showed cytochrome c oxidase-negative fibers and mtDNA multiple deletions, and MRS displayed defective oxidative metabolism in muscle and brain. We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the guanosine triphosphatase domain, each segregating with affected individuals. Fibroblast studies showed a reduced amount of OPA1 protein with normal mRNA expression, fragmented mitochondria, impaired bioenergetics, increased autophagy and mitophagy.
interpretationThe association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of defective mitochondrial dynamics, mtDNA multiple deletions, and altered mitophagy with parkinsonism.
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