OPA1

Summary

Gene Symbol: OPA1
Description: OPA1, mitochondrial dynamin like GTPase
Alias: BERHS, MGM1, MTDPS14, NPG, NTG, largeG, dynamin-like 120 kDa protein, mitochondrial, dynamin-like guanosine triphosphatase, mitochondrial dynamin-like GTPase, optic atrophy 1 (autosomal dominant), optic atrophy protein 1
Species: human
Products:     OPA1

Top Publications

  1. Chen L, Gong Q, Stice J, Knowlton A. Mitochondrial OPA1, apoptosis, and heart failure. Cardiovasc Res. 2009;84:91-9 pubmed publisher
    ..Expression of optic atrophy 1 (OPA1), a mitochondrial fusion protein, was decreased in both human and rat HF, as observed by western blotting...
  2. Schimpf S, Schaich S, Wissinger B. Activation of cryptic splice sites is a frequent splicing defect mechanism caused by mutations in exon and intron sequences of the OPA1 gene. Hum Genet. 2006;118:767-71 pubmed
    Mutations in OPA1 are the most frequent cause underlying autosomal dominant optic atrophy (adOA)...
  3. Yu Wai Man P, Griffiths P, Gorman G, Lourenco C, Wright A, Auer Grumbach M, et al. Multi-system neurological disease is common in patients with OPA1 mutations. Brain. 2010;133:771-86 pubmed publisher
    Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy...
  4. Olichon A, Guillou E, Delettre C, Landes T, Arnauné Pelloquin L, Emorine L, et al. Mitochondrial dynamics and disease, OPA1. Biochim Biophys Acta. 2006;1763:500-9 pubmed
    ..the discovery that two human diseases are caused by mutations in the two mitochondrial pro-fusion genes, MFN2 and OPA1. This review will focus on data concerning the function of OPA1, mutations in which cause optic atrophy, with ..
  5. Yu Wai Man P, Bailie M, Atawan A, Chinnery P, Griffiths P. Pattern of retinal ganglion cell loss in dominant optic atrophy due to OPA1 mutations. Eye (Lond). 2011;25:596-602 pubmed publisher
    The majority of patients with autosomal dominant optic atrophy (DOA) harbour pathogenic OPA1 mutations...
  6. Fan B, Liu K, Wang D, Tham C, Tam P, Lam D, et al. Association of polymorphisms of tumor necrosis factor and tumor protein p53 with primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2010;51:4110-6 pubmed publisher
    ..S-transferase theta 1), MTHFR (5,10-methylenetetrahydrofolate reductase), NOS3 (nitric oxide synthase 3), OPA1 (optic atrophy 1), TNF (tumor necrosis factor), and TP53 (tumor protein p53)...
  7. Griparic L, van der Wel N, Orozco I, Peters P, van der Bliek A. Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. J Biol Chem. 2004;279:18792-8 pubmed
    b>Mgm1 is a member of the dynamin family of GTP-binding proteins. Mgm1 was first identified in yeast, where it affects mitochondrial morphology. The human homologue of Mgm1 is called OPA1...
  8. Schimpf S, Fuhrmann N, Schaich S, Wissinger B. Comprehensive cDNA study and quantitative transcript analysis of mutant OPA1 transcripts containing premature termination codons. Hum Mutat. 2008;29:106-12 pubmed
    Autosomal dominant optic atrophy (adOA) is most commonly caused by mutations in the OPA1 gene...
  9. Darshi M, Mendiola V, Mackey M, Murphy A, Koller A, Perkins G, et al. ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function. J Biol Chem. 2011;286:2918-32 pubmed publisher
    ..RNAi knockdown of ChChd3 in HeLa cells resulted in fragmented mitochondria, reduced OPA1 protein levels and impaired fusion, and clustering of the mitochondria around the nucleus along with reduced growth ..

More Information

Publications84

  1. Powell B, Toomes C, Scott S, Yeung A, Marchbank N, Spry P, et al. Polymorphisms in OPA1 are associated with normal tension glaucoma. Mol Vis. 2003;9:460-4 pubmed
    corrected] To confirm whether specific polymorphisms in intron 8 (IVS8) of the OPA1 gene are found more commonly in patients with normal tension glaucoma (NTG) compared to normal controls...
  2. Hamahata T, Fujimaki T, Fujiki K, Miyazaki A, Mizota A, Murakami A. OPA1 mutations in Japanese patients suspected to have autosomal dominant optic atrophy. Jpn J Ophthalmol. 2012;56:91-7 pubmed publisher
    To report three types of heterozygous mutations in the OPA1 gene in five patients from three families with autosomal dominant optic atrophy (ADOA, MIM#165500). DNA was extracted from the leukocytes of the peripheral blood...
  3. Verny C, Loiseau D, Scherer C, Lejeune P, Chevrollier A, Gueguen N, et al. Multiple sclerosis-like disorder in OPA1-related autosomal dominant optic atrophy. Neurology. 2008;70:1152-3 pubmed publisher
  4. Yao W, Jiao X, Hejtmancik J, Leske M, Hennis A, Nemesure B. Evaluation of the association between OPA1 polymorphisms and primary open-angle glaucoma in Barbados families. Mol Vis. 2006;12:649-54 pubmed
    To investigate whether single nucleotide polymorphisms (SNPs) in the OPA1 gene are associated with two primary open-angle glaucoma (POAG) subgroups: those with elevated intraocular pressure (POAG/IOP) and those with normal tension ..
  5. Li Y, Deng T, Tong Y, Peng S, Dong B, He D. Identification of two novel OPA1 mutations in Chinese families with autosomal dominant optic atrophy. Mol Vis. 2008;14:2451-7 pubmed
    ..Linkage analysis was performed with two microsatellite markers around the OPA1 gene (D3S2305 and D3S3562) in family F1...
  6. Toomes C, Marchbank N, Mackey D, Craig J, Newbury Ecob R, Bennett C, et al. Spectrum, frequency and penetrance of OPA1 mutations in dominant optic atrophy. Hum Mol Genet. 2001;10:1369-78 pubmed
    ..Although heterogeneous, a major locus has been mapped to chromosome 3q28 and the gene responsible, OPA1, was recently identified. We therefore screened a panel of 35 DOA patients for mutations in OPA1...
  7. Pawlikowska P, Orzechowski A. [Role of transmembrane GTPases in mitochondrial morphology and activity]. Postepy Biochem. 2007;53:53-9 pubmed
    ..In this review the authors report on the recent knowledge concerning structural changes of mitochondria with a particular interest to transmembrane GTPases and their role in cellular physiology. ..
  8. Cornille K, Milea D, Amati Bonneau P, Procaccio V, Zazoun L, Guillet V, et al. Reversible optic neuropathy with OPA1 exon 5b mutation. Ann Neurol. 2008;63:667-71 pubmed publisher
    A new c.740G>A (R247H) mutation in OPA1 alternate spliced exon 5b was found in a patient presenting with bilateral optic neuropathy followed by partial, spontaneous visual recovery...
  9. Guillery O, Malka F, Landes T, Guillou E, Blackstone C, Lombes A, et al. Metalloprotease-mediated OPA1 processing is modulated by the mitochondrial membrane potential. Biol Cell. 2008;100:315-25 pubmed
    Human OPA1 (optic atrophy type 1) is a dynamin-related protein of the mitochondrial IMS (intermembrane space) involved in membrane fusion and remodelling...
  10. Ito Y, Nakamura M, Yamakoshi T, Lin J, Yatsuya H, Terasaki H. Reduction of inner retinal thickness in patients with autosomal dominant optic atrophy associated with OPA1 mutations. Invest Ophthalmol Vis Sci. 2007;48:4079-86 pubmed
    ..around the optic disc in patients with autosomal dominant optic atrophy (ADOA) associated with a mutation in the OPA1 gene...
  11. Shimizu S, Mori N, Kishi M, Sugata H, Tsuda A, Kubota N. A novel mutation in the OPA1 gene in a Japanese patient with optic atrophy. Am J Ophthalmol. 2003;135:256-7 pubmed
    To report a novel mutation of the OPA1 gene in a Japanese patient with optic atrophy and to describe the clinical features of the patient. Observational case report...
  12. Fuhrmann N, Alavi M, Bitoun P, Woernle S, Auburger G, Leo Kottler B, et al. Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant optic atrophy. J Med Genet. 2009;46:136-44 pubmed publisher
    ..Although genetic linkage studies point to the OPA1 locus on chromosome 3q28-q29 as by far the most common gene locus, previous screening studies-based on sequencing ..
  13. Huang T, Santarelli R, Starr A. Mutation of OPA1 gene causes deafness by affecting function of auditory nerve terminals. Brain Res. 2009;1300:97-104 pubmed publisher
    ..We sequenced OPA1 gene and recorded cochlear receptor and neural potentials before cochlear implantation...
  14. Yu Wai Man P, Sitarz K, Samuels D, Griffiths P, Reeve A, Bindoff L, et al. OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules. Hum Mol Genet. 2010;19:3043-52 pubmed publisher
    Pathogenic OPA1 mutations cause autosomal dominant optic atrophy (DOA), a condition characterized by the preferential loss of retinal ganglion cells and progressive optic nerve degeneration...
  15. Cohn A, Toomes C, Potter C, Towns K, Hewitt A, Inglehearn C, et al. Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations. Am J Ophthalmol. 2007;143:656-62 pubmed
    We identified families with autosomal dominant optic atrophy (ADOA), determined the number and type of OPA1 mutations, and investigated the phenotypic variation and penetrance in ADOA Australian pedigrees. Cross-sectional genetics study...
  16. Skidd P, Lessell S, Cestari D. Autosomal dominant hereditary optic neuropathy (ADOA): a review of the genetics and clinical manifestations of ADOA and ADOA+. Semin Ophthalmol. 2013;28:422-6 pubmed publisher
    ..The goal of this manuscript is to provide for the general ophthalmologist a practical outline of the genetics and clinical manifestations of ADOA and the ADOA+. ..
  17. Barbet F, Hakiki S, Orssaud C, Gerber S, Perrault I, Hanein S, et al. A third locus for dominant optic atrophy on chromosome 22q. J Med Genet. 2005;42:e1 pubmed
  18. Delettre C, Griffoin J, Kaplan J, Dollfus H, Lorenz B, Faivre L, et al. Mutation spectrum and splicing variants in the OPA1 gene. Hum Genet. 2001;109:584-91 pubmed
    Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy that features low visual acuity leading in many cases to legal blindness...
  19. Satoh M, Hamamoto T, Seo N, Kagawa Y, Endo H. Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria. Biochem Biophys Res Commun. 2003;300:482-93 pubmed
    b>OPA1 is a cause gene for autosomal dominant optic atrophy and possesses eight alternative splicing variants...
  20. Nakamura M, Lin J, Ueno S, Asaoka R, Hirai T, Hotta Y, et al. Novel mutations in the OPA1 gene and associated clinical features in Japanese patients with optic atrophy. Ophthalmology. 2006;113:483-488.e1 pubmed
    ..The disease is genetically heterogeneous, and the OPA1 gene has been identified as the only causative gene...
  21. Amati Bonneau P, Odent S, Derrien C, Pasquier L, Malthiery Y, Reynier P, et al. The association of autosomal dominant optic atrophy and moderate deafness may be due to the R445H mutation in the OPA1 gene. Am J Ophthalmol. 2003;136:1170-1 pubmed
    To examine the involvement of the optic atrophy 1 (OPA1) gene in optic atrophy associated with moderate deafness. Observational case report...
  22. Yu Wai Man P, Stewart J, Hudson G, Andrews R, Griffiths P, Birch M, et al. OPA1 increases the risk of normal but not high tension glaucoma. J Med Genet. 2010;47:120-5 pubmed publisher
    ..The OPA1 gene encodes an inner mitochondrial membrane protein crucial for normal mitochondrial function, and pathogenic ..
  23. Amati Bonneau P, Valentino M, Reynier P, Gallardo M, Bornstein B, Boissière A, et al. OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes. Brain. 2008;131:338-51 pubmed
    Mutations in OPA1, a dynamin-related GTPase involved in mitochondrial fusion, cristae organization and control of apoptosis, have been linked to non-syndromic optic neuropathy transmitted as an autosomal-dominant trait (DOA)...
  24. Olichon A, Baricault L, Gas N, Guillou E, Valette A, Belenguer P, et al. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem. 2003;278:7743-6 pubmed
    b>OPA1 encodes a large GTPase related to dynamins, anchored to the mitochondrial cristae inner membrane, facing the intermembrane space...
  25. Ranieri M, Del Bo R, Bordoni A, Ronchi D, Colombo I, Riboldi G, et al. Optic atrophy plus phenotype due to mutations in the OPA1 gene: two more Italian families. J Neurol Sci. 2012;315:146-9 pubmed publisher
    ..The occurrence of mutations in the gene encoding the dynamin-like GTPase protein Optic Atrophy 1 (OPA1) has been observed in about 60-70% of ADOA cases...
  26. Woo S, Kim D, Kim J, Park S, Ko H, Yoo T. Investigation of the association between OPA1 polymorphisms and normal-tension glaucoma in Korea. J Glaucoma. 2004;13:492-5 pubmed
    b>OPA1, the gene responsible for autosomal dominant optic atrophy, represents a good candidate gene for normal-tension glaucoma (NTG)...
  27. Mabuchi F, Tang S, Kashiwagi K, Yamagata Z, Iijima H, Tsukahara S. The OPA1 gene polymorphism is associated with normal tension and high tension glaucoma. Am J Ophthalmol. 2007;143:125-130 pubmed
    To assess whether genetic polymorphisms of optic atrophy 1 (OPA1) are associated with primary open-angle glaucoma (POAG). Prospective case control association study...
  28. Chen S, Zhang Y, Wang Y, Li W, Huang S, Chu X, et al. A novel OPA1 mutation responsible for autosomal dominant optic atrophy with high frequency hearing loss in a Chinese family. Am J Ophthalmol. 2007;143:186-188 pubmed
    ..Molecular genetic analysis and clinical examinations were performed in a Chinese family with ADOA. Mutations in OPA1 were detected by direct sequencing. Haplotypes were constructed and compared with the phenotypes in the family...
  29. Alexander C, Votruba M, Pesch U, Thiselton D, Mayer S, Moore A, et al. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet. 2000;26:211-5 pubmed
    ..The predominant locus for this disorder (OPA1; MIM 165500) has been mapped to a 1...
  30. Li C, Kosmorsky G, Zhang K, Katz B, Ge J, Traboulsi E. Optic atrophy and sensorineural hearing loss in a family caused by an R445H OPA1 mutation. Am J Med Genet A. 2005;138A:208-11 pubmed
    ..Four genetic loci have been associated with ADOA: OPA1, OPA2, OPA3, and OPA4. Out of these four loci, only one gene has been identified, OPA1...
  31. Amati Bonneau P, Guichet A, Olichon A, Chevrollier A, Viala F, Miot S, et al. OPA1 R445H mutation in optic atrophy associated with sensorineural deafness. Ann Neurol. 2005;58:958-63 pubmed
    The heterozygous R445H mutation in OPA1 was found in five patients with optic atrophy and deafness. Audiometry suggested that the sensorineural deafness resulted from auditory neuropathy...
  32. Duvezin Caubet S, Koppen M, Wagener J, Zick M, Israel L, Bernacchia A, et al. OPA1 processing reconstituted in yeast depends on the subunit composition of the m-AAA protease in mitochondria. Mol Biol Cell. 2007;18:3582-90 pubmed
    The morphology of mitochondria in mammalian cells is regulated by proteolytic cleavage of OPA1, a dynamin-like GTPase of the mitochondrial inner membrane...
  33. Spinazzi M, Cazzola S, Bortolozzi M, Baracca A, Loro E, Casarin A, et al. A novel deletion in the GTPase domain of OPA1 causes defects in mitochondrial morphology and distribution, but not in function. Hum Mol Genet. 2008;17:3291-302 pubmed publisher
    ..cause of inherited optic atrophy, is caused by mutations in the ubiquitously expressed gene optic atrophy 1 (OPA1), involved in fusion and biogenesis of the inner membrane of mitochondria...
  34. Yen M, Wang A, Lin Y, Fann M, Hsiao K. Novel mutations of the OPA1 gene in Chinese dominant optic atrophy. Ophthalmology. 2010;117:392-6.e1 pubmed publisher
    To investigate OPA1 gene mutations in Chinese patients with autosomal dominant optic atrophy and sporadic optic atrophy. Molecular genetic studies and observational case series...
  35. Marchbank N, Craig J, Leek J, Toohey M, Churchill A, Markham A, et al. Deletion of the OPA1 gene in a dominant optic atrophy family: evidence that haploinsufficiency is the cause of disease. J Med Genet. 2002;39:e47 pubmed
  36. Han J, Thompson Lowrey A, Reiss A, Mayorov V, Jia H, Biousse V, et al. OPA1 mutations and mitochondrial DNA haplotypes in autosomal dominant optic atrophy. Genet Med. 2006;8:217-25 pubmed
    ..dominant optic atrophy is a form of blindness, due in part to mutations affecting the mitochondrial-targeted OPA1 gene product. Both OPA1-positive and OPA1-negative families exhibit variable expressivity and incomplete penetrance...
  37. An H, Cho G, Lee J, Paik S, Kim Y, Lee H. Higd-1a interacts with Opa1 and is required for the morphological and functional integrity of mitochondria. Proc Natl Acad Sci U S A. 2013;110:13014-9 pubmed publisher
    ..We demonstrated that Higd-1a functions by specifically binding to Optic atrophy 1 (Opa1), a key element in fusion of the inner membrane...
  38. Mayorov V, Lowrey A, Biousse V, Newman N, Cline S, Brown M. Mitochondrial oxidative phosphorylation in autosomal dominant optic atrophy. BMC Biochem. 2008;9:22 pubmed publisher
    ..optic nerve deterioration, arises predominantly from mutations in the nuclear gene for the mitochondrial GTPase, OPA1. OPA1 localizes to mitochondrial cristae in the inner membrane where electron transport chain complexes are ..
  39. Lodi R, Tonon C, Valentino M, Iotti S, Clementi V, Malucelli E, et al. Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy. Ann Neurol. 2004;56:719-23 pubmed
    Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin-related GTPase, a mitochondrial protein implicated in the formation and maintenance of mitochondrial network and morphology...
  40. Olichon A, Elachouri G, Baricault L, Delettre C, Belenguer P, Lenaers G. OPA1 alternate splicing uncouples an evolutionary conserved function in mitochondrial fusion from a vertebrate restricted function in apoptosis. Cell Death Differ. 2007;14:682-92 pubmed
    ..The intramitochondrial dynamin OPA1, as a potential central actor of these processes, exists as eight isoforms resulting from the alternate splicing ..
  41. Ferre M, Bonneau D, Milea D, Chevrollier A, Verny C, Dollfus H, et al. Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations. Hum Mutat. 2009;30:E692-705 pubmed publisher
    ..by searching for the ten primary LHON-causing mtDNA mutations and examining the entire coding sequences of the OPA1 and OPA3 genes, the two genes currently identified in ADOA...
  42. Liguori M, La Russa A, Manna I, Andreoli V, Caracciolo M, Spadafora P, et al. A phenotypic variation of dominant optic atrophy and deafness (ADOAD) due to a novel OPA1 mutation. J Neurol. 2008;255:127-9 pubmed publisher
  43. Olichon A, Emorine L, Descoins E, Pelloquin L, Brichese L, Gas N, et al. The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett. 2002;523:171-6 pubmed
    Mutations in the OPA1 gene are associated with autosomal dominant optic atrophy...
  44. Schaaf C, Blazo M, Lewis R, Tonini R, Takei H, Wang J, et al. Early-onset severe neuromuscular phenotype associated with compound heterozygosity for OPA1 mutations. Mol Genet Metab. 2011;103:383-7 pubmed publisher
    Pathogenic mutations in the OPA1 gene are the most common identifiable cause of autosomal dominant optic atrophy (DOA), which is characterized by selective retinal ganglion cell loss, a distinctive pattern of temporal pallor of the optic ..
  45. Aung T, Ocaka L, Ebenezer N, Morris A, Brice G, Child A, et al. Investigating the association between OPA1 polymorphisms and glaucoma: comparison between normal tension and high tension primary open angle glaucoma. Hum Genet. 2002;110:513-4 pubmed
    b>OPA1, the gene responsible for autosomal dominant optic atrophy, represents a good candidate gene for glaucoma, as there are similarities in the clinical phenotype and OPA1 is expressed in the optic nerve...
  46. Thiselton D, Alexander C, Taanman J, Brooks S, Rosenberg T, Eiberg H, et al. A comprehensive survey of mutations in the OPA1 gene in patients with autosomal dominant optic atrophy. Invest Ophthalmol Vis Sci. 2002;43:1715-24 pubmed
    To characterize the spectrum of mutations in the OPA1 gene in a large international panel of patients with autosomal dominant optic atrophy (adOA), to improve understanding of the range of functional deficits attributable to sequence ..
  47. Cohn A, Toomes C, Hewitt A, Kearns L, Inglehearn C, Craig J, et al. The natural history of OPA1-related autosomal dominant optic atrophy. Br J Ophthalmol. 2008;92:1333-6 pubmed publisher
    ..However, a large proportion of this disease is accounted for by mutations in OPA1. The aim of this longitudinal study was to investigate disease progression in Australian ADOA patients with ..
  48. Duvezin Caubet S, Jagasia R, Wagener J, Hofmann S, Trifunovic A, Hansson A, et al. Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology. J Biol Chem. 2006;281:37972-9 pubmed
    ..Mutations in the gene encoding OPA1, a protein required for fusion of mitochondria, are associated with hereditary autosomal dominant optic atrophy ..
  49. Baricault L, Segui B, Guégand L, Olichon A, Valette A, Larminat F, et al. OPA1 cleavage depends on decreased mitochondrial ATP level and bivalent metals. Exp Cell Res. 2007;313:3800-8 pubmed
    b>OPA1, an intra-mitochondrial dynamin GTPase, is a key actor of outer and inner mitochondrial membrane dynamic...
  50. Misaka T, Miyashita T, Kubo Y. Primary structure of a dynamin-related mouse mitochondrial GTPase and its distribution in brain, subcellular localization, and effect on mitochondrial morphology. J Biol Chem. 2002;277:15834-42 pubmed
    A new member of the dynamin GTPase family (OPA1) was recently identified in humans and shown to be mutated in patients with dominant optic atrophy...
  51. Stewart J, Hudson G, Yu Wai Man P, Blakeley E, He L, Horvath R, et al. OPA1 in multiple mitochondrial DNA deletion disorders. Neurology. 2008;71:1829-31 pubmed publisher
  52. Arnoult D, Grodet A, Lee Y, Estaquier J, Blackstone C. Release of OPA1 during apoptosis participates in the rapid and complete release of cytochrome c and subsequent mitochondrial fragmentation. J Biol Chem. 2005;280:35742-50 pubmed
    ..Unexpectedly, OPA1, a dynamin-like GTPase of the mitochondrial intermembrane space important for maintaining cristae structure, is co-..
  53. Almind G, Ek J, Rosenberg T, Eiberg H, Larsen M, Lucamp L, et al. Dominant optic atrophy in Denmark - report of 15 novel mutations in OPA1, using a strategy with a detection rate of 90%. BMC Med Genet. 2012;13:65 pubmed publisher
    Investigation of the OPA1 mutation spectrum in autosomal dominant optic atrophy (ADOA) in Denmark. Index patients from 93 unrelated ADOA families were assessed for a common Danish founder mutation (c.2826_2836delinsGGATGCTCCA) inOPA1...
  54. Yu Wai Man P, Shankar S, Biousse V, Miller N, Bean L, Coffee B, et al. Genetic screening for OPA1 and OPA3 mutations in patients with suspected inherited optic neuropathies. Ophthalmology. 2011;118:558-63 pubmed publisher
    ..is one of the most common inherited optic neuropathies, and it is genetically heterogeneous, with mutations in both OPA1 and OPA3 known to cause disease...
  55. Thiselton D, Alexander C, Morris A, Brooks S, Rosenberg T, Eiberg H, et al. A frameshift mutation in exon 28 of the OPA1 gene explains the high prevalence of dominant optic atrophy in the Danish population: evidence for a founder effect. Hum Genet. 2001;109:498-502 pubmed
    ..The gene OPA1, encoding a dynamin-related GTPase, has recently been identified within the genetic linkage interval for the major ..
  56. Votruba M, Moore A, Bhattacharya S. Demonstration of a founder effect and fine mapping of dominant optic atrophy locus on 3q28-qter by linkage disequilibrium method: a study of 38 British Isles pedigrees. Hum Genet. 1998;102:79-86 pubmed
    ..12 highly polymorphic microsatellite markers spanning a region of 12 cM around the dominant optic atrophy locus (OPA1)...
  57. Aung T, Ocaka L, Ebenezer N, Morris A, Krawczak M, Thiselton D, et al. A major marker for normal tension glaucoma: association with polymorphisms in the OPA1 gene. Hum Genet. 2002;110:52-6 pubmed
    ..b>OPA1, the gene responsible for autosomal dominant optic atrophy represents an excellent candidate gene for NTG, as the ..
  58. Almind G, Grønskov K, Milea D, Larsen M, Brøndum Nielsen K, Ek J. Genomic deletions in OPA1 in Danish patients with autosomal dominant optic atrophy. BMC Med Genet. 2011;12:49 pubmed publisher
    ..Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases...
  59. Lee Y, Jeong S, Karbowski M, Smith C, Youle R. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol Biol Cell. 2004;15:5001-11 pubmed
    ..short hairpin RNAs for RNA interference, we manipulated the expression levels of the proteins hFis1, Drp1, and Opa1 that are involved in mitochondrial fission and fusion in mammalian cells, and we characterized their functions in ..
  60. Wolf C, Gramer E, Muller Myhsok B, Pasutto F, Reinthal E, Wissinger B, et al. Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study. BMC Med Genet. 2009;10:91 pubmed publisher
    ..Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population...
  61. Zanna C, Ghelli A, Porcelli A, Karbowski M, Youle R, Schimpf S, et al. OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain. 2008;131:352-67 pubmed publisher
    ..A subset of DOA is caused by mutations in the OPA1 gene, encoding for a dynamin-related GTPase required for mitochondrial fusion...
  62. Ferre M, Amati Bonneau P, Tourmen Y, Malthiery Y, Reynier P. eOPA1: an online database for OPA1 mutations. Hum Mutat. 2005;25:423-8 pubmed
    ..An optic atrophy gene, called OPA1, has been identified in most cases of the disease...
  63. Pierron D, Ferre M, Rocher C, Chevrollier A, Murail P, Thoraval D, et al. OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background. BMC Med Genet. 2009;10:70 pubmed publisher
    ..LHON is associated with mitochondrial DNA (mtDNA) mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mitochondrial protein involved in the mitochondrial inner membrane remodeling...
  64. Delettre C, Lenaers G, Griffoin J, Gigarel N, Lorenzo C, Belenguer P, et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet. 2000;26:207-10 pubmed
    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...
  65. Hudson G, Amati Bonneau P, Blakely E, Stewart J, He L, Schaefer A, et al. Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain. 2008;131:329-37 pubmed
    ..Here we show that a heterozygous mis-sense mutation in OPA1 leads to multiple mtDNA deletions in skeletal muscle and a mosaic defect of cytochrome c oxidase (COX)...
  66. Landes T, Emorine L, Courilleau D, Rojo M, Belenguer P, Arnauné Pelloquin L. The BH3-only Bnip3 binds to the dynamin Opa1 to promote mitochondrial fragmentation and apoptosis by distinct mechanisms. EMBO Rep. 2010;11:459-65 pubmed publisher
    b>Opa1 modulates mitochondrial fusion, cristae structure and apoptosis. The relationships between these functions and autosomal dominant optic atrophy, caused by mutations in Opa1, are poorly defined...
  67. Griparic L, Kanazawa T, van der Bliek A. Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage. J Cell Biol. 2007;178:757-64 pubmed
    The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space, where it facilitates fusion between mitochondria. Apoptosis causes Opa1 release into the cytosol and causes mitochondria to fragment...
  68. Yu Wai Man P, Griffiths P, Burke A, Sellar P, Clarke M, Gnanaraj L, et al. The prevalence and natural history of dominant optic atrophy due to OPA1 mutations. Ophthalmology. 2010;117:1538-46, 1546.e1 pubmed publisher
    ..b>OPA1 genetic testing was performed using a polymerase chain reaction-based sequencing strategy...
  69. Johnston R, Seller M, Behnam J, Burdon M, Spalton D. Dominant optic atrophy. Refining the clinical diagnostic criteria in light of genetic linkage studies. Ophthalmology. 1999;106:123-8 pubmed
    ..This widens the generally accepted diagnostic criteria for this disease. ..
  70. Russo A, Delcassi L, Marchina E, Semeraro F. Correlation between visual acuity and OCT-measured retinal nerve fiber layer thickness in a family with ADOA and an OPA1 mutation. Ophthalmic Genet. 2013;34:69-74 pubmed publisher
    ..869G>A OPA1 mutation...
  71. Liu Y, Schmidt S, Qin X, Gibson J, Munro D, Wiggs J, et al. No association between OPA1 polymorphisms and primary open-angle glaucoma in three different populations. Mol Vis. 2007;13:2137-41 pubmed
    To investigate whether recently described polymorphisms in the optic atrophy 1 gene (OPA1) are associated with primary open-angle glaucoma (POAG) with elevated intraocular pressure in the Caucasian, African-American, and Ghanaian (West ..
  72. Song Z, Chen H, Fiket M, Alexander C, Chan D. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol. 2007;178:749-55 pubmed
    b>OPA1, a dynamin-related guanosine triphosphatase mutated in dominant optic atrophy, is required for the fusion of mitochondria...
  73. Payne M, Yang Z, Katz B, Warner J, Weight C, Zhao Y, et al. Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1. Am J Ophthalmol. 2004;138:749-55 pubmed
    ..Linkage analysis and mutation screening of the optic atrophy 1 gene (OPA1) were performed. Eighteen individuals demonstrated characteristics of the syndrome...
  74. Van Bergen N, Crowston J, Kearns L, Staffieri S, Hewitt A, Cohn A, et al. Mitochondrial oxidative phosphorylation compensation may preserve vision in patients with OPA1-linked autosomal dominant optic atrophy. PLoS ONE. 2011;6:e21347 pubmed publisher
    ..Around 60% of ADOA cases are linked to mutations in the OPA1 gene. OPA1 is a fission-fusion protein involved in mitochondrial inner membrane remodelling...
  75. Ishihara N, Fujita Y, Oka T, Mihara K. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J. 2006;25:2966-77 pubmed
    The dynamin-like GTPase OPA1, a causal gene product of human dominant optic atrophy, functions in mitochondrial fusion and inner membrane remodeling...