Hereditary retinal disease that affects cones first and rods afterwards, distinguishing it from classic rod PRAs. It causes early loss of daytime vision and photophobia, followed by night blindness and progression to complete blindness in young adults. It is specific to the American Pit Bull Terrier and is inherited in a recessive manner. It does not cause ocular pain.

Specific to the American Pit Bull Terrier. No reliable carrier figures are published for the general population; the mutation appears concentrated in related breeding lines and European data are limited.

- Early-onset daytime blindness, preceding night blindness\n- Photophobia and disorientation in bright light\n- Fundus changes in the pigmentary epithelium and tapetal area\n- Progression to complete blindness in young adults\n- Not painful

The crd2 form was described in the American Pit Bull Terrier (Kijas et al. 2004). Goldstein et al. (2013) identified its molecular basis and distinguished it from crd1 (American Staffordshire Terrier, PDE6B): they mapped the locus to CFA33 and, by sequencing positional candidate genes, identified in IQCB1 (NPHP5) a cytosine insertion in exon 10 that segregates recessively in affected families. Aguirre et al. (2021) demonstrated in dogs that NPHP5 gene therapy restores photoreceptor structure and vision, a model of human NPHP5-associated Leber congenital amaurosis. These findings enabled the development of a breed-specific genetic test.

- Test breeding animals before mating\n- Do not mate two carriers: 25% risk of affected homozygotes\n- A carrier may be mated to a clear animal; offspring intended for breeding must be tested\n- Progressively replace carriers with clear offspring without narrowing the gene pool\n- Avoid spreading the allele to lines where it does not exist

Differential diagnosis with other PRAs of the Pit Bull and with deficiency retinopathies (taurine deficiency in unsupplemented diets). The ophthalmological examination may be normal in puppies before clinical onset; the genetic test identifies carriers before signs appear. A crd2 animal tested as clear does not exclude other forms of PRA.

1. Kijas JW et al. (2004) Cloning of the canine ABCA4 gene and evaluation in canine cone-rod dystrophies and progressive retinal atrophies. Mol Vis 10:223-232. PMID: 15064680
2. Goldstein O et al. (2013) IQCB1 and PDE6B mutations cause similar early onset retinal degenerations in two closely related terrier dog breeds. Invest Ophthalmol Vis Sci 54(10):7005-7019. PMID: 24045995
3. Aguirre GD et al. (2021) Gene therapy reforms photoreceptor structure and restores vision in NPHP5-associated Leber congenital amaurosis. Mol Ther 29(8):2456-2468. PMID: 33781914
4. OMIA:001675-9615. crd2; PRA-NPHP5(IQCB1) in Canis lupus familiaris. https://omia.org/OMIA001675/9615/