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Canine Mendelian disease record

Cone-Rod Dystrophy 2 (Discovered in the Pit Bull Terrier; crd2)

Cone-Rod Dystrophy 2 (Discovered in the Pit Bull Terrier; crd2). Autosomal recessive. Observed in 2 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,664 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:001675-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human Senior-Loken syndrome 5

This is the canine counterpart of Senior-Loken syndrome 5 in people. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: Any Senior-Loken syndrome in which the cause of the disease is a mutation in the IQCB1 gene.

In humans it is also called: SLSN5, IQCB1 Senior-Loken syndrome, Senior-Loken syndrome type 5.

MONDO:0012225 OMIM 609254

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

This disorder has been named in OMIA on the basis of the review by Miyadera et al. (2012)

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)

Molecular genetics

Sequencing of a likely candidate gene (IQCB1, also called NPHP5) 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".

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"

History

This disorder was first reported and given the symbol crd2 by Kijas et al. (2004), in a family of Pit Bull Terriers.

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."

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 609254 Gene · OMIM 609237

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001675-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 13.

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Cone-Rod Dystrophy 2 (Discovered in the Pit Bull Terrier; crd2) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Cone-Rod Dystrophy 2 (Discovered in the Pit Bull Terrier; crd2) looks like in your dog's breed.
Carrier frequency by breed

Top 2 well-sampled breeds (n ≥ 50)

Maximum per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%1%2%
American Staffordshire Terrier0.32% · n 42,792
Boxer<0.1% · n 4,557
n = 47,349 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Cone-Rod Dystrophy 2 (Discovered in the Pit Bull Terrier; crd2) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
American Staffordshire Terrier 0.32% 42,792
Boxer <0.1% 4,557

264 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Penetrance

From genotype to phenotype

Carrier status is not the same as disease status. Penetrance is the fraction of at-risk dogs that develop the phenotype. The Donner 2023 S4 table tracks this for 1 variant(s) underlying this disease in the cohort.

At-risk dogs evaluated
3
Phenotype confirmed
3
Penetrance range
not yet quantifiable

Fewer than 20 at-risk dogs evaluated; too few to state a penetrance figure.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome is governed by penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:001675-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001675-9615 · Donner et al. 2023