Scientific Disease Database
Leber‘s Congenital Amaurosis

Recent update from: 28.11.06

Disease Gene locus MIM Gene Gene MIM MoI Assignment

Linked Marker [cM] Remarks References
Childhood-onset severe retinal dystrophy COSRD
RDH12
ar 14q23.3


Consanguineous Austrian kindreds
Retinal dystrophy affecting rods and cones
Onset in early childhood
Progression to legal blindness 18-25y. 		(11)
(16)

LCA
CRX 120970 ad 19q13.3

D19S47- D19S49
  • 2 single heterozygous mutations in 2 patients
    		• (6)
    (18)
    type 1 LCA1 204000 RetGC1 600179 ar 17p13

    		D17S796- D17S938- D17S1353- D17S786
  • 17/24 homozygous / 4/24 compound heterozygous / 3/24 single heterozygous
  • 22 different mutations in 24 families
    		• (17)
    (1)
    (18)
    early-onset severe retinal dystrophy, type2 LCA2 204000 RPE65 180069 ar 1q31

    		D1S1665- D1S207
  • 13 different mutations in 10 families
    		• (9)
    (14)
    (18)
    type 3 LCA3 604232

    		ar 14q24

    		D14S606
    D14S610
    D14S74 [10]
    • Saudi Arabian Families
    • PDP
    		 (20)
    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
    		• (10)
    (19)
    (18)
    type 5 LCA5 604537

    		ar 6q11-16

    		D6S1619- D6S1596- [LCA5: D6S391- D6S1056 - D6S1707- D6S251- D6S445]- D6S1627- D6S1644- D6S1631- D6S450- D6S300- D6S1716
  • Old River Brethren
  • Indian
    		• (4)
    (15)
    type 6 LCA6
    		CRB1 604210 ar 1q31-32.1



    		(2)
    (13)
    type 7 LCA7
    		RPGRIP1 605446 ar 14q11


  • 8 patients in a sample of 142
    		• (5)
    (8)
    early-onset severe retinal dystrophy LCA8 604863 LRAT 604863 ar 4q31.2

    		D4S2999- D4S3021- D4S1548- LRAT- D4S2962- D4S1586
  • Resembles RPE65-phenotype
    		• (21)
    type 9 LCA9


    		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
    		• (12)
    type 10 LCA10 204000 CEP-290 610142 ar 12q21.3

    		rs950017 - CEP-290 - D12S1710- D12S95 - rs1385060 - D12S1345
    		(3)
    Early-onset Retinal Degeneration RD3
    		C1ORF36 180040 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
    		• (7)

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

    References

    1. 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
    2. 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
    3. 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
    4. 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
    5. 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
    6. 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 [letter]. 1998; Nat.Genet. 18: 311-312.
      Link Goto Top
    7. Friedman,J.S., Chang,B., Kananbiran,C., Chakarova,C., Singh,H.P., Jalali,S., Hawes,N., Branham,K., Othman,M., Filipova,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. Goto Top
    8. 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
    9. 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
    10. 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
    11. 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
    12. 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
    13. 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
    14. 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
    15. 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
    16. 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
    17. 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
    18. 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
    19. 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
    20. 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
    21. 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
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    Disease Database Page     		This site is maintained and edited by
    Dr. rer. medic. Markus Preising, Dipl.Biol.
    Molecular Genetics Laboratory
    Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics
    University of Regensburg
    Head: Prof. Dr. med. Birgit Lorenz