OMIA:001675-9615 : Cone-rod dystrophy 2 in Canis lupus familiaris
In other species: black-footed cat
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 609237 (gene) , 609254 (trait)
Links to MONDO diseases: No links.
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.
|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|
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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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|606||American Pit Bull Terrier||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|
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.
|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.|
|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.|
|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 .|
- 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