OPA1, encoding a dynamin-related GTPase is mutated in autosomal dominant optic atrophy linked to chromosome 3q28

Alexander, Cornelius B.; Votruba, Marcela; Pesch, Uea; Thiselton, DL; Mayer, S. A.; Moore, AT; Rodríguez, Martín González; Kellner, Ulrich; Leo-Kottler, Beate; Auburger, G.; Bhattacharya, SS; Wissinger, Bernd

doi:10.1016/s0002-9394(01)00853-4

Cited by 114 publications

(141 citation statements)

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“…Opa1 was initially identified as the gene mutated in ADOA, the most common optic atrophy affecting retinal ganglion cells and leading to reduced visual acuity [7,8]. To date, more than 100 mutations of Opa1 have been identified, and almost 50% of the mutations result in premature truncation of the Opa1 protein [121].…”

Section: Mitochondrial Dynamics In Genetic Neurodegenerative Diseasesmentioning

confidence: 99%

“…Mitochondrial dynamics (fission and fusion) control processes associated with the biogenesis, subcellular localization and distribution of mitochondria as well as their morphology [2,3]. Several principal controllers of mitochondrial dynamics have been identified [4][5][6][7][8][9] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

“…Dysfunction of mitochondrial dynamics and resulting disease can emanate not only from mutations of the genes encoding fission-or fusion-related proteins, but also, as our group has recently shown, from posttranslational protein modifications that regulate their stability and activity. Mfn1/2 and Opa1 are affected in patients with Charcot-Marie-Tooth neuropathy type 2A (CMT2A) [21][22][23] and autosomal dominant optic atrophy (ADOA), respectively [7,8,17]. Drp1 activity can be regulated by phosphorylation, S-nitrosylation, sumoylation and ubiqutination, while Opa1 is activated by proteolytic processing [24][25][26][27][28][29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial dynamics in cell death and neurodegeneration

Cho

Nakamura

Lipton

2010

Cell. Mol. Life Sci.

254

204

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Mitochondria are highly dynamic organelles that continuously undergo two opposite processes, fission and fusion. Mitochondrial dynamics influence not only mitochondrial morphology, but also mitochondrial biogenesis, mitochondrial distribution within the cell, cell bioenergetics, and cell injury or death. Drp1 mediates mitochondrial fission, whereas Mfn1/2 and Opa1 control mitochondrial fusion. Neurons require large amounts of energy to carry out their highly specialized functions. Thus, mitochondrial dysfunction is a prominent feature in a variety of neurodegenerative diseases. Mutations of Mfn2 and Opa1 lead to neuropathies such as Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. Moreover, both Aβ peptide and mutant huntingtin protein induce mitochondrial fragmentation and neuronal cell death. In addition, mutants of Parkinson's disease-related genes also show abnormal mitochondrial morphology. This review highlights our current understanding of abnormal mitochondrial dynamics relevant to neuronal synaptic loss and cell death in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease.

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Section: Mitochondrial Dynamics In Genetic Neurodegenerative Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitochondrial dynamics in cell death and neurodegeneration

Cho

Nakamura

Lipton

2010

Cell. Mol. Life Sci.

254

204

View full text Add to dashboard Cite

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“…Mutations in the OPA1 gene have largely been associated with autosomal dominant optic atrophy (ADOA; OMIM 165500), which is typified by atrophy of the retinal ganglion cells [4,5]. This neuro-ophthalmic degeneration typically manifests with early onset (first decade) insidious bilateral visual loss (defects in colour vision and paracentral scotomas) and an absence of extraocular symptoms.…”

Section: Introductionmentioning

confidence: 99%

A novel OPA1 mutation causing variable age of onset autosomal dominant optic atrophy plus in an Australian family

2015

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Pathogenic mutations in the OPA1 gene can be associated with Autosomal Dominant Optic Atrophy (ADOA). In approximately 20 % of patients with OPA1 mutations, a more complex neurodegenerative disorder with extraocular manifestations, known as ADOA Plus, can arise. 12 members of a multigenerational family were assessed clinically and screened for a genetic mutation in OPA1. Eight family members displayed manifestations consistent with ADOA Plus and four did not. Affected members of the oldest available generation displayed the most severe phenotype, which included severe optic atrophy, deafness, ptosis, ophthalmoplegia, proximal myopathy, neuropathy and ataxia. The next generation was less severely affected but several members displayed manifestations only after the fifth decade. Genetic analysis revealed a heterozygous variant in the OPA1 gene (c.1053T>A, p.Asp351Glu) that segregated with disease. The affected family members described here exhibited visual loss later than is typical for OPA1-related disease, as well as later onset of other neurological abnormalities in the fifth or sixth decades of life that progressed to severe neurological disability by the seventh decade. These findings expand the clinical spectrum of OPA1-related disease associated with a novel OPA1 mutation.

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“…After obtaining informed consent, we examined both patients for the OPA1 gene, which was recently identified as the causative gene of ADOA [1,2], and we found a novel mutation in one patient. Unfortunately the previously published Japanese family with optic atrophy associated with negative ERGs [4] was not available for this study.…”

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confidence: 99%