Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 163500 (trait) , 613801 (trait) , 180072 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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 (Dog) (VBO_0200055).
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: