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Disease Database

Leber Congenital Amaurosis and other Early Onset Severe Retinal Dystrophies

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
Early-onset Retinal Degeneration and pituary dysfunction EORD
OTX2 600037 ar 14q21-q22



Link(14)
Early-onset Retinal Degeneration LCA 604863 LRAT 604863 ar 4q31.2

D4S2999- D4S3021- D4S1548- LRAT- D4S2962- D4S1586
  • Resembles RPE65-phenotype
    		• Link(27)
    type 1 LCA1 204000 GUCY2D 600179 ar 17p13

    		D17S796- D17S938- D17S1353- D17S786
  • 17/24 homozygous / 4/24 compound heterozygous / 3/24 single heterozygous
  • 22 different mutations in 24 families
    		• Link(23)
    Link(3)
    Link(24)
    Early-onset Retinal Degeneration LCA2 204000 RPE65 180069 ar 1p31

    		D1S1665- D1S207
  • 13 different mutations in 10 families
    		• Link(12)
    Link(19)
    Link(24)
    type 3 LCA3 604232 SPATA7 609868 ar 14q31.3

    		D14S606
    D14S610
    D14S74 [10]
    • Saudi Arabian Families
    • PDP
    		 Link(26)
    Link(28)
    Link(17)
    Link(21)
    type 4 LCA4 604393 AIPL1 604392 ar 17p13.1

    		D17S849 - D17S960
    D17S796
    D17S1881
    D17S1353
  • 3 European families
  • 2 Pakistani families
    • Members carrying mutations are heterozygous for markers D17S1353 and D17S960
  • 3/8 homozygous / 1/8 compound heterozygous / 4/8 single heterozygous
  • 6 different mutations in 8 patients
    		• Link(13)
    Link(25)
    Link(24)
    type 5 LCA5 604537 C6ORF152 611408 ar 6q14

    		D6S1619- D6S1596- [LCA5: D6S391- D6S1056 - D6S1707- D6S251- D6S445]- D6S1627- D6S1644- D6S1631- D6S450- D6S300- D6S1716
  • Old River Brethren
  • Indian
  • Pakistani
    		• Link(7)
    Link(20)
    Link(5)
    type 6 LCA6
    		RPGRIP1 605446 ar 14q11


  • 8 patients in a sample of 142
    		• Link(8)
    Link(11)
    type 7 LCA7
    		CRX 120970 ad 19q13.3

    		D19S47- D19S49
  • 2 single heterozygous mutations in 2 patients
    		• Link(9)
    Link(24)
    type 8 LCA8
    		CRB1 604210 ar 1q31-32.1



    		Link(4)
    Link(18)
    type 9 LCA9 608553

    		ar 1p36

    		CATC051- D1S2132- D1S1646- D1S2663- D1S2694- D1S548- D1S2666- D1S508- [- D1S1612- D1S503- D1S450- D1S2736- D1S2740- D1S489- D1S434- D1S1597- D1S228- ]- D1S2834- D1S507- D1S2728- D1S3669- D1S1592- ATA47D07
  • Pakistani
    		• Link(16)
    type 10 LCA10 204000 CEP290 610142 ar 12q21.3

    		rs950017 - CEP-290 - D12S1710- D12S95 - rs1385060 - D12S1345
    		Link(6)
    type 11 LCA11 204000 IMPDH1 146690 ad 7q31.3


    		Link(2)
    Early-onset Retinal Degeneration LCA12
    		C1ORF36 610412 ar 1q32


  • Mutation screen in
    • 461 retinopathy patients from North America
      • 30 COD
      • 15 LCA
    • 103 indian RD
    • 302 UK RD
      • 177 ADRP
      • 96 ARRP
      • 29CRD
    • 15 Scandinavian CRD
    Rare cause of retinopathy
    		• Link(10)
    Childhood-onset severe retinal dystrophy LCA13
    		RDH12
    		ar 14q23.3


    		Consanguineous Austrian kindreds
    Retinal dystrophy affecting rods and cones
    Onset in early childhood
    Progression to legal blindness 18-25y.     		Link(15)
    Link(22)
    type 14 LCA14 204000 CABP4 608965 ar 11q13


  • Saudi Arabia
    		• Link(1)
    MoI = Mode of Inheritance: a: autosomal, ad: autosomal dominant, ar: autosomal recessive, xl: x-linked, mt: mitochondrial

    References

    1. Aldahmesh,M.A., Al-Owain,M., Alqahtani,F., Hazzaa,S., and Alkuraya,F.S. A null mutation in CABP4 causes Leber's congenital amaurosis-like phenotype. 2010; Mol.Vis. 16:207-12.: 207-212.
      Link Goto Top
    2. Bowne,S.J., Liu,Q., Sullivan,L.S., Zhu,J., Spellicy,C.J., Rickman,C.B., Pierce,E.A., and Daiger,S.P. Why do mutations in the ubiquitously expressed housekeeping gene IMPDH1 cause retina-specific photoreceptor degeneration? 2006; Invest Ophthalmol Vis.Sci. 47: 3754-3765.
      Link Goto Top
    3. Camuzat,A., Rozet,J.M., Dollfus,H., Gerber,S., Perrault,I., Weissenbach,J., Munnich,A., and Kaplan,J. Evidence of genetic heterogeneity of Leber's congenital amaurosis (LCA) and mapping of LCA1 to chromosome 17p13. 1996; Hum.Genet. 97: 798-801.
      Link Goto Top
    4. den Hollander,A.I., Heckenlively,J.R., van den Born,L.I., de Kok,Y.J., Velde-Visser,S.D., Kellner,U., Jurklies,B., van Schooneveld,M.J., Blankenagel,A., Rohrschneider,K., Wissinger,B., Cruysberg,J.R., Deutman,A.F., Brunner,H.G., Apfelstedt-Sylla,E., Hoyng,C.B., and Cremers,F.P. Leber Congenital Amaurosis and Retinitis Pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. 2001; Am.J.Hum.Genet. 69: 198-203.
      Link Goto Top
    5. den Hollander,A.I., Koenekoop,R.K., Mohamed,M.D., Arts,H.H., Boldt,K., Towns,K.V., Sedmak,T., Beer,M., Nagel-Wolfrum,K., McKibbin,M., Dharmaraj,S., Lopez,I., Ivings,L., Williams,G.A., Springell,K., Woods,C.G., Jafri,H., Rashid,Y., Strom,T.M., van der,Z.B., Gosens,I., Kersten,F.F., van,W.E., Veltman,J.A., Zonneveld,M.N., van Beersum,S.E., Maumenee,I.H., Wolfrum,U., Cheetham,M.E., Ueffing,M., Cremers,F.P., Inglehearn,C.F., and Roepman,R. Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis. 2007; Nat.Genet. 39: 889-895.
      Link Goto Top
    6. den Hollander,A.I., Koenekoop,R.K., Yzer,S., Lopez,I., Arends,M.L., Voesenek,K.E., Zonneveld,M.N., Strom,T.M., Meitinger,T., Brunner,H.G., Hoyng,C.B., van den Born,L.I., Rohrschneider,K., and Cremers,F.P. Mutations in the CEP290 (NPHP6) Gene Are a Frequent Cause of Leber Congenital Amaurosis. 2006; Am J Hum Genet. 79: 556-561.
      Link Goto Top
    7. Dharmaraj,S., Li,Y., Robitaille,J.M., Silva,E., Zhu,D., Mitchell,T.N., Maltby,L.P., Baffoe-Bonnie,A.B., and Maumenee,I.H. A Novel Locus for Leber Congenital Amaurosis Maps to Chromosome 6q. 2000; Am.J.Hum.Genet. 66: 319-326.
      Link Goto Top
    8. Dryja,T.P., Adams,S.M., Grimsby,J.L., McGee,T.L., Hong,D.H., Li,T., Andreasson,S., and Berson,E.L. Null RPGRIP1 alleles in patients with leber congenital amaurosis. 2001; Am.J.Hum.Genet. 68: 1295-1298.
      Link Goto Top
    9. Freund,C.L., Wang,Q.L., Chen,S., Muskat,B.L., Wiles,C.D., Sheffield,V.C., Jacobson,S.G., McInnes,R.R., Zack,D.J., and Stone,E.M. De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. 1998; Nat.Genet. 18: 311-312.
      Link Goto Top
    10. Friedman,J.S., Chang,B., Kannabiran,C., Chakarova,C., Singh,H.P., Jalali,S., Hawes,N.L., Branham,K., Othman,M., Filippova,E., Thompson,D.A., Webster,A.R., Andreasson,S., Jacobson,S.G., Bhattacharya,S.S., Heckenlively,J.R., and Swaroop,A. Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration. 2006; Am.J.Hum.Genet. 79: 1059-1070.
      Link Goto Top
    11. Gerber,S., Perrault,I., Hanein,S., Barbet,F., Ducroq,D., Ghazi,I., Martin-Coignard,D., Leowski,C., Homfray,T., Dufier,J.L., Munnich,A., Kaplan,J., and Rozet,J.M. Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene allows the identification of mutations underlying Leber congenital amaurosis. 2001; Eur.J.Hum.Genet. 9: 561-571.
      Link Goto Top
    12. Gu,S., Thompson,D.A., Srisailapathy Srikumari,C.R., Lorenz,B., Finckh,U., Nicoletti,A., Murthy,K.R., Rathmann,M., Kumaramanickavel,G., Denton,M.J., and Gal,A. Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. 1997; Nat.Genet. 17: 194-197.
      Link Goto Top
    13. Hameed,A., Khaliq,S., Ismail,M., Ebenezer,N.D., Jordon,T., Mehdi,S.Q., Payne,A.M., and Bhattacharya,S.S. A novel locus for Leber congential amaurosis (LCA) with anterior keratoconus mapping to chromosome 17p13. 1999; Am.J.Hum.Genet. 65: A255 Goto Top
    14. Henderson,R.H., Williamson,K.A., Kennedy,J.S., Webster,A.R., Holder,G.E., Robson,A.G., Fitzpatrick,D.R., van,H., V, and Moore,A.T. A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction. 2009; Mol.Vis. 15:2442-7.: 2442-2447.
      Link Goto Top
    15. Janecke,A.R., Thompson,D.A., Utermann,G., Becker,C., Hubner,C.A., Schmid,E., McHenry,C.L., Nair,A.R., Ruschendorf,F., Heckenlively,J., Wissinger,B., Nurnberg,P., and Gal,A. Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset severe retinal dystrophy. 2004; Nat.Genet. 36: 850-854.
      Link Goto Top
    16. Keen,T.J., Mohamed,M.D., McKibbin,M., Rashid,Y., Jafri,H., Maumenee,I.H., and Inglehearn,C.F. Identification of a locus (LCA9) for Leber's congenital amaurosis on chromosome 1p36. 2003; Eur.J.Hum.Genet. 11: 420-423.
      Link Goto Top
    17. Li,Y., Wang,H., Peng,J., Gibbs,R.A., Lewis,R.A., Lupski,J.R., Mardon,G., and Chen,R. Mutation survey of known LCA genes and loci in the Saudi Arabian population. 2009; Invest Ophthalmol Vis.Sci. 50: 1336-1343.
      Link Goto Top
    18. Lotery,A.J., Jacobson,S.G., Fishman,G.A., Weleber,R.G., Fulton,A.B., Namperumalsamy,P., Heon,E., Levin,A.V., Grover,S., Rosenow,J.R., Kopp,K.K., Sheffield,V.C., and Stone,E.M. Mutations in the CRB1 gene cause Leber congenital amaurosis. 2001; Arch.Ophthalmol. 119: 415-420.
      Link Goto Top
    19. Marlhens,F., Bareil,C., Griffoin,J.M., Zrenner,E., Amalric,P., Eliaou,C., Liu,S.Y., Harris,E., Redmond,T.M., Arnaud,B., Claustres,M., and Hamel,C.P. Mutations in RPE65 cause Leber's congenital amaurosis. 1997; Nat.Genet. 17: 139-141.
      Link Goto Top
    20. Mohamed,M.D., Topping,N.C., Jafri,H., Raashed,Y., McKibbin,M.A., and Inglehearn,C.F. Progression of phenotype in Leber's congenital amaurosis with a mutation at the LCA5 locus. 2003; Br.J Ophthalmol. 87: 473-475.
      Link Goto Top
    21. Perrault,I., Hanein,S., Gerard,X., Delphin,N., Fares-Taie,L., Gerber,S., Pelletier,V., Merce,E., Dollfus,H., Puech,B., foort-Dhellemmes,S., Petersen,M.D., Zafeiriou,D., Munnich,A., Kaplan,J., Roche,O., and Rozet,J.M. Spectrum of SPATA7 mutations in Leber congenital amaurosis and delineation of the associated phenotype. 2010; Hum.Mutat. 31: E1241-E1250
      Link Goto Top
    22. Perrault,I., Hanein,S., and Kaplan,J. L'amaurose congenitale de Leber: les retinol-deshydrogenases au banc des accuses. 2004; Med.Sci.(Paris). 20: 1066-1068.
      Link Goto Top
    23. Perrault,I., Rozet,J.M., Calvas,P., Gerber,S., Camuzat,A., Dollfus,H., Chatelin,S., Souied,E., Ghazi,I., Leowski,C., Bonnemaison,M., Le Paslier,D., Frezal,J., Dufier,J.L., Pittler,S., Munnich,A., and Kaplan,J. Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis. 1996; Nat.Genet. 14: 461-464.
      Link Goto Top
    24. Perrault,I., Rozet,J.M., Gerber,S., Ghazi,I., Ducroq,D., Souied,E., Leowski,C., Bonnemaison,M., Dufier,J.L., Munnich,A., and Kaplan,J. Spectrum of retGC1 mutations in Leber's congenital amaurosis. 2000; Eur.J.Hum.Genet. 8: 578-582.
      Link Goto Top
    25. Sohocki,M.M., Bowne,S.J., Sullivan,L.S., Blackshaw,S., Cepko,C.L., Payne,A.M., Bhattacharya,S.S., Khaliq,S., Qasim Mehdi,S., Birch,D.G., Harrison,W.R., Elder,F.F., Heckenlively,J.R., and Daiger,S.P. Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis. 2000; Nat.Genet. 24: 79-83.
      Link Goto Top
    26. Stockton,D.W., Lewis,R.A., Abboud,E.B., Al Rajhi,A., Jabak,M., Anderson,K.L., and Lupski,J.R. A novel locus for Leber congenital amaurosis on chromosome 14q24. 1998; Hum.Genet. 103: 328-333.
      Link Goto Top
    27. Thompson,D.A., Li,Y., McHenry,C.L., Carlson,T.J., Ding,X., Sieving,P.A., Apfelstedt-Sylla,E., and Gal,A. Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy. 2001; Nat.Genet. 28: 123-124.
      Link Goto Top
    28. Wang,H., den Hollander,A.I., Moayedi,Y., Abulimiti,A., Li,Y., Collin,R.W., Hoyng,C.B., Lopez,I., Bray,M., Lewis,R.A., Lupski,J.R., Mardon,G., Koenekoop,R.K., and Chen,R. Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa. 2009; Am.J.Hum.Genet. 84: 380-387.
      Link Goto Top
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