OMIA 000882-9615 : Rod-cone dysplasia 1 in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 163500 , 613801

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1993

Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012)

Species-specific symbol: rcd1

Molecular basis: By cloning and sequencing a very likely candidate gene (based on detailed biochemical comparisons of affected and normal Irish Setter dogs), Suber et al. (1993) reported a causative mutation as being "a nonsense amber mutation at codon 807 (a G-->A transition converting TGG to TAG), which was confirmed to be present in putative exon 21 of the affected beta-subunit gene [PDE6B]. The premature stop codon truncates the beta subunit by 49 residues, thus removing the C-terminal domain that is required for posttranslational processing and membrane association."

Breed: Irish Setter.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PDE6B phosphodiesterase 6B, cGMP-specific, rod, beta Canis lupus familiaris 3 NC_006585.3 (91775372..91746571) PDE6B Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

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
Irish Setter Rod-cone dysplasia 1 PDE6B nonsense (stop-gain) CanFam3.1 3 g.91747713G>A c.2421G>A p.W807* 1993 8387203 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
2016 Pichard, V., Provost, N., Mendes-Madeira, A., Libeau, L., Hulin, P., Tshilenge, K.T., Biget, M., Ameline, B., Deschamps, J.Y., Weber, M., Le Meur, G., Colle, M.A., Moullier, P., Rolling, F. :
AAV-mediated Gene Therapy Halts Retinal Degeneration in PDE6β-deficient Dogs. Mol Ther 24:867-76, 2016. Pubmed reference: 26857842. DOI: 10.1038/mt.2016.37.
2014 Genini, S., Guziewicz, K.E., Beltran, W.A., Aguirre, G.D. :
Altered miRNA expression in canine retinas during normal development and in models of retinal degeneration. BMC Genomics 15:172, 2014. Pubmed reference: 24581223. DOI: 10.1186/1471-2164-15-172.
2013 Genini, S., Beltran, W.A., Aguirre, G.D. :
Up-regulation of tumor necrosis factor superfamily genes in early phases of photoreceptor degeneration. PLoS One 8:e85408, 2013. Pubmed reference: 24367709. DOI: 10.1371/journal.pone.0085408.
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.
2005 Güven, D., Weiland, J.D., Fujii, G., Mech, B.V., Mahadevappa, M., Greenberg, R., Roizenblatt, R., Qiu, G., Labree, L., Wang, X., Hinton, D., Humayun, M.S. :
Long-term stimulation by active epiretinal implants in normal and RCD1 dogs. J Neural Eng 2:S65-73, 2005. Pubmed reference: 15876657. DOI: 10.1088/1741-2560/2/1/009.
2004 Panzan, CQ., Guven, D., Weiland, JD., Lakhanpal, RR., Javaheri, M., de Juan, E., Humayun, MS. :
Retinal thickness in normal and RCD1 dogs using optical coherence tomography. Ophthalmic Surg Lasers Imaging 35:485-93, 2004. Pubmed reference: 15580972.
1999 Aguirre, G.D., Baldwin, V., Weeks, K.M., Acland, G.M., Ray, K. :
Frequency of the codon 807 mutation in the cGMP phosphodiesterase beta-subunit gene in Irish setters and other dog breeds with hereditary retinal degeneration Journal of Heredity 90:143-147, 1999. Pubmed reference: 9987922.
Zuleger, B., Kuhnlein, P., Muller, E. :
A case-report on a carrier of the PRA-causing mutation in Irish Setters in Germany [German] Kleintierpraxis 44:211-212, 1999.
1997 Kommonen, B., Kylma, T., Karhunen, U., Dawson, W.W., Penn, J.S. :
Impaired retinal function in young labrador retriever dogs heterozygous for late onset rod-cone degeneration Vision Research 37:365-370, 1997. Pubmed reference: 9135869.
1995 Mclaughlin, M.E., Ehrhart, T.L., Berson, E.L., Dryja, T.P. :
Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa Proceedings of the National Academy of Sciences of the United States of America 92:3249-3253, 1995. Pubmed reference: 7724547.
Petersen-Jones, S.M., Clements, P.J.M., Barnett, K.C., Sargan, D.R. :
Incidence of the gene mutation causal for rod-cone dysplasia type 1 in Irish setters in the UK Journal of Small Animal Practice 36:310-314, 1995. Pubmed reference: 7474961.
Ray, K., Baldwin, V.J., Acland, G.M., Aguirre, G.D. :
Molecular diagnostic tests for ascertainment of genotype at the rod cone dysplasia 1 (rcd1) locus in Irish setters Current Eye Research 14:243-247, 1995. Pubmed reference: 7796608.
Sargan, D.R. :
Research in canine and human genetic disease Journal of Medical Genetics 32:751-754, 1995. Pubmed reference: 8544201.
1994 Ray, K., Baldwin, V.J., Acland, G.M., Blanton, S.H., Aguirre, G.D. :
Cosegregation of codon 807 mutation of the canine rod cGMP phosphodiesterase beta gene and rcd1 Investigative Ophthalmology & Visual Science 35:4291-4299, 1994. Pubmed reference: 8002249.
1993 Clements, P.J.M., Gregory, C.Y., Petersen-Jones, S.M., Sargan, D.R., Bhattacharya, S.S. :
Confirmation of the rod cGMP phosphodiesterase beta subunit (PDE beta) nonsense mutation in affected rcd-1 Irish setters in the UK and development of a diagnostic test Current Eye Research 12:861-866, 1993. Pubmed reference: 8261797.
Suber, M.L., Pittler, S.J., Qin, N., Wright, G.C., Holcombe, V., Lee, R.H., Craft, C.M., Lolley, R.N., Baehr, W., Hurwitz, R.L. :
Irish Setter Dogs Affected with Rod/Cone Dysplasia Contain a Nonsense Mutation in the Rod cGMP Phosphodiesterase beta- Subunit Gene Proceedings of the National Academy of Sciences of the United States of America 90:3968-3972, 1993. Pubmed reference: 8387203.
1992 Farber, D.B., Danciger, J.S., Aguirre, G. :
The beta-Subunit of Cyclic GMP Phosphodiesterase Messenger RNA Is Deficient in Canine Rod-Cone Dysplasia-1 Neuron 9:349-356, 1992. Pubmed reference: 1323314.
1990 Farber, D.B., Danciger, J.S., Aguirre, G. :
Early mRNA defect in Irish setter dog retina Investigative Opthalmology and Visual Sciences 31 (Supplement):310 only, 1990.
1989 Acland, G.M., Fletcher, R.T., Gentleman, S., Chader, G.J., Aguirre, G.D. :
Non-allelism of three genes (rcd1, rcd2, erd) for early-onset hereditary retinal degeneration Experimental Eye Research 49:983-998, 1989. Pubmed reference: 2558906.
1988 Barbehenn, E., Gagnon, C., Noelker, D., Aguirre, G., Chader, G. :
Inherited rod-cone dysplasia: abnormal distribution of cyclic GMP in visual cells of affected Irish setters Experimental Eye Research 46:149-159, 1988. Pubmed reference: 2895011.
1982 Aguirre, G.D., Farber, D., Lolley, R., O'Brien, P., Alligood, J., Fletcher, R.T., Chader, G.J. :
Retinal degeneration in the dog. III. Abnormal cyclic nucleotide metabolism in rod-cone dysplasia Experimental Eye Research 35:625-642, 1982. Pubmed reference: 6295790.
1980 Buyukmihci, N., Aguirre, G., Marshall, J. :
Retinal degenerations in the dog. II. Development of the retina in rod-cone dysplasia Experimental Eye Research 30:575-591, 1980. Pubmed reference: 7409013.
1978 Aguirre, G.D., Lolley, R., Farber, D., Fletcher, T., Chader, G.J. :
Rod–cone dysplasia in Irish setter dogs: a defect in cyclic GMP metabolism in visual cells Science 201:1133-1135, 1978.
1975 Aguirre, G.D., Rubin, L.F. :
The electroretinogram in dogs with inherited cone degeneration Investigative Ophthalmology 14:840-847, 1975. Pubmed reference: 1081095.
1953 Parry, H.B. :
Degenerations of the dog retina. I. Structure and development of the retina of the normal dog British Journal of Ophthalmology 37:385-404, 1953. Pubmed reference: 13059279.
Parry, H.B. :
Degeneration of the dog retina. II. Generalised progressive atrophy of hereditary origin British Journal of Ophthalmology 37:487-502, 1953. Pubmed reference: 13081944.

Edit History


  • Created by Frank Nicholas on 12 Sep 2005
  • Changed by Frank Nicholas on 29 Nov 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 29 Aug 2012
  • Changed by Frank Nicholas on 15 Oct 2016