OMIA 001674-9615 : Cone-rod dystrophy 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: 2013

Species-specific symbol: crd1

History: This disorder was first reported and given the symbol crd1 by Kijas et al. (2004), in a family of American Staffordshire Terriers.

Mapping: By conducting a GWAS on 17 affected and 18 control dogs from a colony of American Staffordshire Terriers segregating the disorder, each genotyped for 173,662 SNPs on the Illumina HD Canine SNP chip, Goldstein et al. (2013) mapped crd1 to a region of chromosome CFA3. Homozygosity mapping identified a 1.05 Mb candidate block at the telomeric end of CFA3.

Molecular basis: Sequencing of a likely candidate gene (PDE6B) in the candidate block (see Mapping section) enabled Goldstein et al. (2013) to identify the causal mutation to be "a three-bases-deletion . . . in exon 21 of the gene in the affected dogs (c.2404-2406del, CFA3: 94,574,289-94,574,291), in-frame with the protein . . . . This mutation would result in a deletion of the amino acid asparagine at position 802 of the protein (p.802del)".

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 Pit Bull Terriers, but these authors showed that the two disorders are not allelic, and consequently named the other disorder crd2 (see OMIA 001675-9615)

Pathology: As reported by Goldstein et al. (2013): "At 11 weeks postnatal age, the earliest time-point examined, the outer nuclear layer (ONL) of the crd1-affected retina was reduced to between 6 to 8 nuclei in thickness . . . . Photoreceptor IS [inner segments] and OS [outer segments] were distinctly distorted, with rod IS more severely affected than those of cones. Relatively few OS of either rods or cones were recognizable, and the profiles that comprised the putative ISL and OSL (i.e. the layer between the outer limiting membrane and the retinal pigment epithelium) were sparse and disarrayed (Figure 2C). By 20 months of age, the crd1-affected retina was in an advanced state of degeneration, with less than 2-3 ONL cells"

Breed: American Staffordshire terrier.

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
American Staffordshire terrier Cone-rod dystrophy 1 PDE6B deletion, small (<=20) CanFam 2 3 g.94574289_94574291 c.2404_2406del p.802del 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.
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