OMIA:001675-9615 : Retinal atrophy - Cone-rod dystrophy 2 in Canis lupus familiaris (dog)

In other species: black-footed cat

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609237 (gene) , 609254 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

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

Species-specific symbol: crd2

History: This disorder was first reported and given the symbol crd2 by Kijas et al. (2004), in a family of Pit Bull Terriers.

Mapping: By conducting a GWAS on 15 affected and 13 control dogs from a colony of Pit Bull Terriers segregating the disorder, each genotyped for approximately 127,000 SNPs on the Affymetrix canine SNP chip v2 (yielding 60,245 informative SNPs), Goldstein et al. (2013) mapped crd2 to a "a 4.4 Mb interval on CFA33 (22,690,750-27,122,415)". Homozygosity mapping identified a 2.3 Mb candidate block, namely "CFA33: 27,065,615-29,382,529".

Molecular basis: Sequencing of a likely candidate gene (IQCB1) in the candidate block (see Mapping section) enabled Goldstein et al. (2013) to identify the causal mutation to be "3 cytosines compared to 2 in the wild-type allele (CFA33: 28,120,686-28,120,687 . . . . This insertion, c.952-953insC, causes a frameshift that results in a change of 12 amino acids (amino acids 319-330) and introduction of a premature stop codon (p.S319IfsX12). This would yield a predicted 330 amino acid protein, in which only 318 are identical to normal".

Clinical features: As reported by Kijas et al. (2004): "early, severe, and rapidly progressive loss of cone function accompanied by progressive rod loss that is only relatively slower". Very similar clinical signs were reported by Kijas et al. (2004) in a family of American Staffordshire Terriers, but these authors showed that the two disorders are not allelic, and consequently named the other disorder crd1 (see OMIA 001674-9615)

Pathology: As reported by Goldstein et al. (2013): "By 12 weeks of age, . . . the ONL [outer nuclear layer] of the crd2-affected retina comprised only 5-7 layers; cone and rod inner and outer segments were present but distinctly abnormal, disorganized, and reduced in size and number compared to age-matched normal retina . . . . At 20 months of age, no IS [inner segments] and OS [outer segments] were present in the crd2-affected retina, and the ONL was thinned to nowhere more than 2 cell layers"

Control: Aguirre et al. (2021): "show that adeno-associated virus (AAV)-mediated NPHP5 [IQCB1] gene augmentation of mutant canine retinas at the time of active degeneration and peak cell death stably restores photoreceptor structure, function, and vision with either the canine or human NPHP5 [IQCB1] transgenes."

Breed: American Pit Bull Terrier (Dog) (VBO_0200054).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
IQCB1 IQ motif containing B1 Canis lupus familiaris 33 NC_051837.1 (25348614..25282284) IQCB1 Homologene, Ensembl , NCBI gene


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.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
606 American Pit Bull Terrier (Dog) Cone-rod dystrophy 2 IQCB1 insertion, small (<=20) Naturally occurring variant CanFam3.1 33 g.25078909_25078910insC c.952_53insC p.(S319Ifs*12) 2013 24045995

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2021). OMIA:001675-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2024 Taskin, H.O., Wivel, J., Aguirre, G.D., Beltran, W.A., Aguirre, G.K. :
Cone-driven, geniculocortical responses in canine models of outer retinal disease. Transl Vis Sci Technol 13:18, 2024. Pubmed reference: 38241039. DOI: 10.1167/tvst.13.1.18.
2023 Taskin, H.O., Wivel, J., Aguirre, G.D., Beltran, W.A., Aguirre, G.K. :
Cone-driven, geniculo-cortical responses in canine models of outer retinal disease. bioRxiv :2023.12.13.571523, 2023. Pubmed reference: 38168165. DOI: 10.1101/2023.12.13.571523.
2022 Badiei, A., Beltran, W.A., Aguirre, G.D. :
Altered transsulfuration pathway enzymes and redox homeostasis in inherited retinal degenerative diseases. Exp Eye Res 215:108902, 2022. Pubmed reference: 34954206. DOI: 10.1016/j.exer.2021.108902.
2021 Aguirre, G.D., Cideciyan, A.V., Dufour, V.L., Ripolles-García, A., Sudharsan, R., Swider, M., Nikonov, R., Iwabe, S., Boye, S.L., Hauswirth, W.W., Jacobson, S.G., Beltran, W.A. :
Gene therapy reforms photoreceptor structure and restores vision in NPHP5-associated Leber congenital amaurosis. Mol Ther , 2021. Pubmed reference: 33781914. DOI: 10.1016/j.ymthe.2021.03.021.
Genetics Committee of the American College of Veterinary Opthalmologists :
The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition , 2021.
2016 Downs, L.M., Scott, E.M., Cideciyan, A.V., Iwabe, S., Dufour, V., Gardiner, K.L., Genini, S., Marinho, L.F., Sumaroka, A., Kosyk, M.S., Swider, M., Aguirre, G.K., Jacobson, S.G., Beltran, W.A., Aguirre, G.D. :
Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused by NPHP5 mutation. Hum Mol Genet , 2016. Pubmed reference: 27506978. DOI: 10.1093/hmg/ddw254.
Palanova, A. :
The genetics of inherited retinal disorders in dogs: implications for diagnosis and management. Vet Med (Auckl) 7:41-51, 2016. Pubmed reference: 30050836. DOI: 10.2147/VMRR.S63537.
2013 Goldstein, O., Mezey, J.G., Schweitzer, P.A., Boyko, A.R., Gao, C., Bustamante, C.D., Jordan, J.A., Aguirre, G.D., Acland, G.M. :
IQCB1 and PDE6B mutations cause similar early onset retinal degenerations in two closely related terrier dog breeds. Invest Ophthalmol Vis Sci 54:7005-19, 2013. Pubmed reference: 24045995. DOI: 10.1167/iovs.13-12915.
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.
2004 Kijas, J.W., Zangerl, B., Miller, B., Nelson, J., Kirkness, E.F., Aguirre, G.D., Acland, G.M. :
Cloning of the canine ABCA4 gene and evaluation in canine cone-rod dystrophies and progressive retinal atrophies. Mol Vis 10:223-32, 2004. Pubmed reference: 15064680.

Edit History

  • Created by Frank Nicholas on 07 Dec 2011
  • Changed by Frank Nicholas on 07 Dec 2011
  • Changed by Frank Nicholas on 24 Sep 2013
  • Changed by Frank Nicholas on 01 Oct 2015
  • Changed by Imke Tammen2 on 19 Apr 2021
  • Changed by Imke Tammen2 on 18 Aug 2021