OMIA 001222-9615 : Leber congenital amaurosis in Canis lupus familiaris

In other species: domestic cat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 204100

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1998

Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012). It is also known as retinal pigment epithelial dystrophy.

Species-specific symbol: LCA(csnb)

Molecular basis: Despite much molecular detective work, the cause of this particular disorder in Swedish Briards remained a mystery for many years. In two papers, Veske et al. (1997) excluded four genes as the source of the mutation causing the disorder: arrestin, rhodopsin, beta-subunit of photoreceptor-specific phosphodiesterase by segregation analysis, and rod photoreceptor cgmp-gated cation channel alpha-subunit. In 1998, Veske et al. also excluded the gene for retinal guanylate cyclase isoform E. Then, finally, in 1998, Aguirre et al. showed that the disorder is due to 4bp deletion in the gene for a 65-kilodalton microsomal protein expressed in retinal pigment epithelium (RPE). The gene, called RPE65, had recently been shown to be mutated in the human homologue of this disorder (see link to OMIM on this page). The discovery was confirmed by Veske et al. (1999).

Clinical features: Kondo et al. (2015) reported that the diagnosis of this disorder as congenital stationary night blindness by Narfström et al. (1989) was actually incorrect, and that the disorder described in this OMIA entry is not actually congenital stationary night blindness. Kondo et al. (2015) do not provide any suggestions as to the correct diagnosis.

Breed: Briard.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
RPE65 retinal pigment epithelium-specific protein 65kDa Canis lupus familiaris 6 NC_006588.3 (76887399..76911133) RPE65 Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Briard Leber congenital amaurosis (congenital stationary night blindness) RPE65 deletion, small (<=20) 4bp deletion in RPE65 1998 9808841

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2017 Mowat, F.M., Gervais, K.J., Occelli, L.M., Annear, M.J., Querubin, J., Bainbridge, J.W., Smith, A.J., Ali, R.R., Petersen-Jones, S.M. :
Early-Onset Progressive Degeneration of the Area Centralis in RPE65-Deficient Dogs. Invest Ophthalmol Vis Sci 58:3268-3277, 2017. Pubmed reference: 28662231. DOI: 10.1167/iovs.17-21930.
2015 Kondo, M., Das, G., Imai, R., Santana, E., Nakashita, T., Imawaka, M., Ueda, K., Ohtsuka, H., Sakai, K., Aihara, T., Kato, K., Sugimoto, M., Ueno, S., Nishizawa, Y., Aguirre, G.D., Miyadera, K. :
A Naturally Occurring Canine Model of Autosomal Recessive Congenital Stationary Night Blindness. PLoS One 10:e0137072, 2015. Pubmed reference: 26368928. DOI: 10.1371/journal.pone.0137072.
2014 Klein, D., Mendes-Madeira, A., Schlegel, P., Rolling, F., Lorenz, B., Haverkamp, S., Stieger, K. :
Immuno-histochemical analysis of rod and cone reaction to RPE65 deficiency in the inferior and superior canine retina. PLoS One 9:e86304, 2014. Pubmed reference: 24466015. DOI: 10.1371/journal.pone.0086304.
2013 Cideciyan, A.V., Jacobson, S.G., Beltran, W.A., Hauswirth, W.W., Aguirre, G.D. :
Reply to Townes-Anderson: RPE65 gene therapy does not alter the natural history of retinal degeneration. Proc Natl Acad Sci U S A 110:E1706, 2013. Pubmed reference: 23789127.
Cideciyan, A.V., Jacobson, S.G., Beltran, W.A., Sumaroka, A., Swider, M., Iwabe, S., Roman, A.J., Olivares, M.B., Schwartz, S.B., Komáromy, A.M., Hauswirth, W.W., Aguirre, G.D. :
Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci U S A 110:E517-25, 2013. Pubmed reference: 23341635. DOI: 10.1073/pnas.1218933110.
Townes-Anderson, E. :
Increased levels of gene therapy may not be beneficial in retinal disease. Proc Natl Acad Sci U S A 110:E1705, 2013. Pubmed reference: 23553840. DOI: 10.1073/pnas.1303746110.
2012 Miyadera, K., Acland, G.M., Aguirre, G.D. :
Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61, 2012. Pubmed reference: 22065099. DOI: 10.1007/s00335-011-9361-3.
2010 Gearhart, PM., Gearhart, C., Thompson, DA., Petersen-Jones, SM. :
Improvement of Visual Performance With Intravitreal Administration of 9- cis -Retinal in Rpe65 -Mutant Dogs. Arch Ophthalmol :, 2010. Pubmed reference: 20837787. DOI: 10.1001/archophthalmol.2010.210.
Hernandez, M., Pearce-Kelling, S., Rodriguez, DF., Aguirre, GD., Vecino, E. :
Altered Expression of Retinal Molecular Markers in the Canine RPE65 Model of Leber Congenital Amaurosis. Invest Ophthalmol Vis Sci 51:6793-802, 2010. Pubmed reference: 20671290. DOI: 10.1167/iovs.10-5213.
Lhériteau, E., Libeau, L., Mendes-Madeira, A., Deschamps, J.Y., Weber, M., Le Meur, G., Provost, N., Guihal, C., Moullier, P., Rolling, F. :
Regulation of retinal function but nonrescue of vision in RPE65-deficient dogs treated with doxycycline-regulatable AAV vectors. Mol Ther 18:1085-93, 2010. Pubmed reference: 20354505. DOI: 10.1038/mt.2010.46.
2009 Cai, X., Conley, SM., Naash, MI. :
RPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet 30:57-62, 2009. Pubmed reference: 19373675. DOI: 10.1080/13816810802626399.
Jacobs, JB., Dell'Osso, LF., Wang, ZI., Acland, GM., Bennett, J. :
Using the NAFX to measure the effectiveness over time of gene therapy in canine LCA. Invest Ophthalmol Vis Sci 50:4685-92, 2009. Pubmed reference: 19458334. DOI: 10.1167/iovs.09-3387.
2008 Bennicelli, J., Wright, JF., Komaromy, A., Jacobs, JB., Hauck, B., Zelenaia, O., Mingozzi, F., Hui, D., Chung, D., Rex, TS., Wei, Z., Qu, G., Zhou, S., Zeiss, C., Arruda, VR., Acland, GM., Dell'Osso, LF., High, KA., Maguire, AM., Bennett, J. :
Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer. Mol Ther 16:458-65, 2008. Pubmed reference: 18209734. DOI: 10.1038/sj.mt.6300389.
Narfström, K., Seeliger, M., Lai, C.M., Vaegan, Katz, M., Rakoczy, E.P., Remé, C. :
Morphological aspects related to long-term functional improvement of the retina in the 4 years following rAAV-mediated gene transfer in the RPE65 null mutation dog. Adv Exp Med Biol 613:139-46, 2008. Pubmed reference: 18188938.
2007 Aguirre, G.K., Komáromy, A.M., Cideciyan, A.V., Brainard, D.H., Aleman, T.S., Roman, A.J., Avants, B.B., Gee, J.C., Korczykowski, M., Hauswirth, W.W., Acland, G.M., Aguirre, G.D., Jacobson, S.G. :
Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation. PLoS Med 4:e230, 2007. Pubmed reference: 17594175. DOI: 10.1371/journal.pmed.0040230.
2006 Jacobs, JB., Dell'Osso, LF., Hertle, RW., Acland, GM., Bennett, J. :
Eye movement recordings as an effectiveness indicator of gene therapy in RPE65-deficient canines: implications for the ocular motor system. Invest Ophthalmol Vis Sci 47:2865-75, 2006. Pubmed reference: 16799026. DOI: 10.1167/iovs.05-1233.
Jacobson, SG., Acland, GM., Aguirre, GD., Aleman, TS., Schwartz, SB., Cideciyan, AV., Zeiss, CJ., Komaromy, AM., Kaushal, S., Roman, AJ., Windsor, EA., Sumaroka, A., Pearce-Kelling, SE., Conlon, TJ., Chiodo, VA., Boye, SL., Flotte, TR., Maguire, AM., Bennett, J., Hauswirth, WW. :
Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection. Mol Ther 13:1074-84, 2006. Pubmed reference: 16644289. DOI: 10.1016/j.ymthe.2006.03.005.
2005 Acland, GM., Aguirre, GD., Bennett, J., Aleman, TS., Cideciyan, AV., Bennicelli, J., Dejneka, NS., Pearce-Kelling, SE., Maguire, AM., Palczewski, K., Hauswirth, WW., Jacobson, SG. :
Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther 12:1072-82, 2005. Pubmed reference: 16226919. DOI: 10.1016/j.ymthe.2005.08.008.
Narfstrom, K., Katz, M., Bragadottir, R., Rakoczy, EP., Seeliger, M. :
Assessment of structure and function over a 3-year period after gene transfer in RPE65-/- dogs. Doc Ophthalmol 111:39-48, 2005. Pubmed reference: 16502306. DOI: 10.1007/s10633-005-3159-0.
2003 Ford, M., Bragadottir, R., Rakoczy, P.E., Narfstrom, K. :
Gene transfer in the RPE65 null mutation dog: relationship between construct volume, visual behavior and electroretinographic (ERG) results Documenta Ophthalmologica 107:79-86, 2003. Pubmed reference: 12906125.
Narfstrom, K., Bragadottir, R., Redmond, TM., Rakoczy, PE., van Veen, T., Bruun, A. :
Functional and structural evaluation after AAV.RPE65 gene transfer in the canine model of Leber's congenital amaurosis. Adv Exp Med Biol 533:423-30, 2003. Pubmed reference: 15180294.
Narfstrom, K., Katz, M.L., Bragadottir, R., Seeliger, M., Boulanger, A., Redmond, T.M., Caro, L., Lai, C.M., Rakoczy, P.E. :
Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog Investigative Ophthalmology & Visual Science 44:1663-72, 2003. Pubmed reference: 12657607.
Narfstrom, K., Katz, ML., Ford, M., Redmond, TM., Rakoczy, E., Bragadottir, R. :
In vivo gene therapy in young and adult RPE65-/- dogs produces long-term visual improvement. J Hered 94:31-7, 2003. Pubmed reference: 12692160.
2002 MuLellan, G.J., Elks, R., Lybaert, P., Watte, C., Moore, D.L., Bedford, P.G.C. :
Vitamin E deficiency in dogs with retinal pigment epithelial dystrophy Veterinary Record 151:663-667, 2002. Pubmed reference: 12498409.
Switonski, M., Konieczny, P., Klukowska, J., Janyga, B., Aguirre, G. :
Microdeletion in the RPE65 gene causing hereditary retinal dystrophy (HRD) disease segregates in the Polish population of Briards Medycyna Weterynaryjna 58:946-949, 2002.
2001 Acland, GM., Aguirre, GD., Ray, J., Zhang, Q., Aleman, TS., Cideciyan, AV., Pearce-Kelling, SE., Anand, V., Zeng, Y., Maguire, AM., Jacobson, SG., Hauswirth, WW., Bennett, J. :
Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28:92-5, 2001. Pubmed reference: 11326284. DOI: 10.1038/88327.
Gould, D. :
Congenital stationary night blindness in briards in the UK Veterinary Record 148:351-352, 2001. Pubmed reference: 11316301.
Thomas, R., Holmes, N., Binns, M. :
Congenital stationary night blindness in briards in the UK Veterinary Record 148:488, 2001. Pubmed reference: 11334084.
1999 Veske, A., Nilsson, S.E.G., Narfstrom, K., Gal, A. :
Retinal dystrophy of Swedish briard briard-beagle dogs is due to a 4-bp deletion in RPE65 Genomics 57:57-61, 1999. Pubmed reference: 10191083. DOI: 10.1006/geno.1999.5754.
1998 Aguirre, G.D., Baldwin, V., Pearce-Kelling, S., Narfström, K., Ray, K., Acland, G.M. :
Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis 4:23, 1998. Pubmed reference: 9808841.
Veske, A., Nilsson, S.E.G., Gal, A. :
Organization of the canine gene encoding the E isoform of retinal guanylate cyclase (CGC-E) and exclusion of its involvement in the inherited retinal dystrophy of the Swedish Briard and Briard-Beagle dogs Biochimica et Biophysica Acta - Biomembranes 1372:69-77, 1998.
1997 Anderson, R.E., Maude, M.B., Narfstrom, K., Nilsson, S.E.G. :
Lipids of plasma, retina, and retinal pigment epithelium in Swedish Briard dogs with a slowly progressive retinal dystrophy Experimental Eye Research 64:181-187, 1997. Pubmed reference: 9176051. DOI: 10.1006/exer.1996.0195.
Chaudieu, G. :
Cases of inherited retinal pigmented epithelium dystrophy in wire-haired fox terrier - an original clinical study and a review of literature [French] Revue de Medecine Veterinaire 148:537-546, 1997.
Veske, A., Narfstrom, K., Finckh, U., Sargan, D.R., Nilsson, S.E.G., Gal, A. :
Isolation of canine retinal arrestin cDNA and exclusion of three candidate genes for Swedish Briard retinal dystrophy Current Eye Research 16:270-274, 1997. Pubmed reference: 9088745.
Veske, A., Nilsson, S.E.G., Gal, A. :
Characterization of canine rod photoreceptor cgmp-gated cation channel alpha-subunit gene and exclusion of its involvement in the hereditary retinal dystrophy of Swedish Briards Gene 202:115-119, 1997. Pubmed reference: 9427553.
1996 Lightfoot, R.M., Cabral, L., Gooch, L., Bedford, P.G.C., Boulton, M.E. :
Retinal pigment epithelial dystrophy in Briard dogs Research in Veterinary Science 60:17-23, 1996. Pubmed reference: 8745249.
1994 Wrigstad, A., Narfström, K., Nilsson, S.E. :
Slowly progressive changes of the retina and retinal pigment epithelium in Briard dogs with hereditary retinal dystrophy. A morphological study. Doc Ophthalmol 87:337-54, 1994. Pubmed reference: 7851218.
1989 Narfstrom, K., Wrigstad, A., Nilsson, S.E.G. :
The Briard Dog - A New Animal Model of Congenital Stationary Night Blindness British Journal of Ophthalmology 73:750-756, 1989. Pubmed reference: 2804031.

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  • Created by Frank Nicholas on 27 Oct 2009
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  • Changed by Frank Nicholas on 07 Dec 2011
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  • Changed by Frank Nicholas on 20 Jan 2016