OMIA 001675-9615 : Cone-rod dystrophy 2 in Canis lupus familiaris

In other species: black-footed cat

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 609237 , 204000

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"

Breed: American pit bull terrier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
IQCB1 IQ motif containing B1 Canis lupus familiaris 33 NC_006615.3 (25113252..25046975) IQCB1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
American pit bull terrier Cone-rod dystrophy 2 IQCB1 insertion, small (<=20) CanFam 2 33 g.28120686-28120687 c.952-953insC p.S319IfsX12 2013 24045995

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 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.

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