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Disease Database

Optic Atrophy

Recent update from: 24.03.2010

This site is maintained and edited by
Dr. rer. medic. Markus Preising, Dipl.Biol.
Laboratory of Molecular Ophthalmology
Department of Opthalmology
Justus-Liebig-University, Giessen, Germany
Head: Prof. Dr. med. Birgit Lorenz

Disease Gene locus MIM Gene Gene MIM MoI Assignment

Linked Marker [cM] Remarks References
Leber´s optic atrophy LHON 535000

mt mitochondrial

T14484C is the predominant mutation in French-Canadian families Link(7)
Kjer type
OPA1 165500 OPA1 605290 ad 3q28

cen- D3S2418- D3S1314- D3S1601- [1.4 D3S3669- (300 kb)- D3S1523- (400 kb)- D3S2305- D3S3642- D3S3590- D3S3562]- D3S2748-D3S1305- D3S1265- tel
  • 43 - 98% penetrance
  • 5 Danish families
  • Primary degeneration of retinal ganglion cells
  • Ascending atrophy of the optic nerve
  • Results from haploinsufficiency
  • Incomplete penetrance in ADOA families with complete genetic counselling
  • Link(1)
    X-linked OPA2 311050

    xl Xp11.4-11.21


    Kjer type
    OPA3 165300 OPA3 606580 ad 19q13.2-q13.3

    Kjer type
    OPA4 605293

    ad 18q12.2-3

    D18S877- D18S47- D18S456- D18S57- D18S468- [D18S34- D18S548- D18S861- D18S479 3 cM]- D18S51- D18S64
  • Visual Acuity 20/20 - 6/200
  • German descendants in Maryland
  • 32 living affected
  • Visual acuity deteriorates with age
  • Acquired blue-yellow defects are typical but hardly recognized by Ishihara-plates
  • Not fully penetrant
  • Link(11)
    congenital or early infantile, autosomal recessive OPA5 258500

    ar 22q12.3

    infantile, autosomal recessive OPA6, ROA1 258500

    ar 8q21-q22

    D8S1702, D8S270, D8S1794
  • Consanguineous French
  • Link(4)
    recessive non syndromic OPA7 612989 TMEM126A 612988 ar 11q14.1-q21

    MoI = Mode of Inheritance: a: autosomal, ad: autosomal dominant, ar: autosomal recessive, xl: x-linked, mt: mitochondrial


    1. Alexander,C., Votruba,M., Pesch,U.E., Thiselton,D.L., Mayer,S., Moore,A., Rodriguez,M., Kellner,U., Leo-Kottler,B., Auburger,G., Bhattacharya,S.S., and Wissinger,B. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. 2000; Nat.Genet. 26: 211-215.
      Link Goto Top
    2. Anikster,Y., Kleta,R., Shaag,A., Gahl,W.A., and Elpeleg,O. Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews. 2001; Am.J.Hum.Genet. 69: 1218-1224.
      Link Goto Top
    3. Assink,J.J., Tijmes,N.T., ten Brink,J.B., Oostra,R.J., Riemslag,F.C., de Jong,P.T., and Bergen,A.A. A gene for X-linked optic atrophy is closely linked to the Xp11.4- Xp11.2 region of the X chromosome. 1997; Am.J.Hum.Genet. 61: 934-939. Goto Top
    4. Barbet,F., Gerber,S., Hakiki,S., Perrault,I., Hanein,S., Ducroq,D., Tanguy,G., Dufier,J.L., Munnich,A., Rozet,J.M., and Kaplan,J. A first locus for isolated autosomal recessive optic atrophy (ROA1) maps to chromosome 8q. 2003; Eur.J.Hum.Genet. 11: 966-971.
      Link Goto Top
    5. Barbet,F., Hakiki,S., Orssaud,C., Gerber,S., Perrault,I., Hanein,S., Ducroq,D., Dufier,J.L., Munnich,A., Kaplan,J., and Rozet,J.M. A third locus for dominant optic atrophy on chromosome 22q. 2005; J.Med.Genet. 42: e1
      Link Goto Top
    6. Bonneau,D., Souied,E., Gerber,S., Rozet,J.M., D'Haens,E., Journel,H., Plessis,G., Weissenbach,J., Munnich,A., and Kaplan,J. No evidence of genetic heterogeneity in dominant optic atrophy. 1995; J.Med.Genet. 32: 951-953.
      Link Goto Top
    7. Brown,M.D., Sun,F., and Wallace,D.C. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage. 1997; Am.J.Hum.Genet. 60: 381-387.
      Link Goto Top
    8. Hanein,S., Perrault,I., Roche,O., Gerber,S., Khadom,N., Rio,M., Boddaert,N., Jean-Pierre,M., Brahimi,N., Serre,V., Chretien,D., Delphin,N., Fares-Taie,L., Lachheb,S., Rotig,A., Meire,F., Munnich,A., Dufier,J.L., Kaplan,J., and Rozet,J.M. TMEM126A, encoding a mitochondrial protein, is mutated in autosomal-recessive nonsyndromic optic atrophy. 2009; Am.J.Hum.Genet. 84: 493-498.
      Link Goto Top
    9. Johns,D.R. Genotype-phenotype interaction in Leber's hereditary optic neuropathy. 1996; Invest.Ophthalmol.Vis.Sci. 37: S922 Goto Top
    10. Jonasdottir,A., Eiberg,H., Kjer,B., Kjer,P., and Rosenberg,T. Refinement of the dominant optic atrophy locus (OPA1) to a 1.4- cM interval on chromosome 3q28-3q29, within a 3-Mb YAC contig. 1997; Hum.Genet. 99: 115-120.
      Link Goto Top
    11. Kerrison,J.B., Arnould,V.J., Ferraz Sallum,J.M., Vagefi,M.R., Barmada,M.M., Li,Y., Zhu,D., and Maumenee,I.H. Genetic heterogeneity of dominant optic atrophy, Kjer type: Identification of a second locus on chromosome 18q12.2-12.3. 1999; Arch Ophthalmol. 117: 805-810.
      Link Goto Top
    12. Macmillan,C., Johns,T.A., Fu,K., and Shoubridge,E.A. Predominance of the T14484C Mutation in French-Canadian Families with Leber Hereditary Optic Neuropathy Is Due to a Founder Effect. 2000; Am.J.Hum.Genet. 66: 332-335.
      Link Goto Top
    13. Norby,S. Mutation-specific PCR: a rapid and inexpensive diagnostic method, as exemplified by mitochondrial DNA analysis in Leber's hereditary optic neuropathy. 1993; DNA Cell Biol. 12: 549-552.
      Link Goto Top
    14. Reynier,P., Amati-Bonneau,P., Verny,C., Olichon,A., Simard,G., Guichet,A., Bonnemains,C., Malecaze,F., Malinge,M.C., Pelletier,J.B., Calvas,P., Dollfus,H., Belenguer,P., Malthiery,Y., Lenaers,G., and Bonneau,D. OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract. 2004; J.Med.Genet. 41: e110
      Link Goto Top
    15. Smith,K.H., Johns,D.R., Heher,K.L., and Miller,N.R. Heteroplasmy in Leber's hereditary optic neuropathy. 1993; Arch.Ophthalmol. 111: 1486-1490.
      Link Goto Top
    16. Stoilova,D., Child,A., Desai,S.P., and Sarfarazi,M. Refinement of the locus for autosomal dominant juvenile optic atrophy to a 2 cM region on 3q28. 1997; Ophthalm.Genet. 18: 1-6.
      Link Goto Top
    17. Thiselton,D.L., Alexander,C., Taanman,J.W., Brooks,S., Rosenberg,T., Eiberg,H., Andreasson,S., Van Regemorter,N., Munier,F.L., Moore,A.T., Bhattacharya,S.S., and Votruba,M. A comprehensive survey of mutations in the OPA1 gene in patients with autosomal dominant optic atrophy. 2002; Invest.Ophthalmol.Vis.Sci. 43: 1715-1724.
      Link Goto Top
    18. Vilkki,J., Savontaus,M.L., Nikoskelainen,E.K., and Vilkki,J. Genetic heterogeneity in Leber hereditary optic neuroretinopathy revealed by mitochondrial DNA polymorphism. 1989; Am.J.Hum.Genet. 45: 206-211.
      Link Goto Top
    19. Votruba,M., Moore,A.T., and Bhattacharya,S.S. Genetic refinement of dominant optic atrophy (OPA1) locus to within a 2 cM interval of chromosome 3q. 1997; J.Med.Genet. 34: 117-121.
      Link Goto Top
    20. Votruba,M., Moore,A.T., and Bhattacharya,S.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. 1998; Hum.Genet. 102: 79-86.
      Link Goto Top

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