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Cone degeneration (CD) - German Shorthaired Pointer

Ocular · Dog

Recessive retinal disease of the German Shorthaired Pointer that produces selective and progressive loss of cone photoreceptors, responsible for daytime vision and visual acuity. Affected dogs develop daytime blindness (hemeralopia) and photophobia from 8-12 weeks, while retaining vision in low-light conditions. The ocular fundus remains normal for years, so the electroretinogram is key for clinical diagnosis. It does not cause ocular pain.
Inheritance patternAutosomal recessive
Gene / MutationCNGB3 c.784G>A p.(Asp262Asn) in the German Shorthaired Pointer (CanFam3.1 NC_006611.3:g.32837065C>T; OMIA001365-9615, variant 27; Sidjanin 2002, PMID 12140185). In the Alaskan Malamute and Miniature Australian Shepherd the cause is the cd^AMAL deletion that removes all exons of CNGB3 (OMIA variant 631; Sidjanin 2002). The alleles are named cd^AMAL (deletion) and cd^GSPT (D262N); do not use the «CD1/CD2» notation.
PenetranceComplete penetrance in homozygotes from 8-12 weeks; heterozygotes are asymptomatic carriers. The combination of a null deletion (cd^AMAL) and the missense variant (cd^GSPT) in compound heterozygosity would be functionally null, but there are no published cases documenting it; do not present it as an established fact.
Codevniv
Turnaround time15 days
Price52,60 €

Incidence

Specific to the German Shorthaired Pointer (cd^GSPT variant, D262N). The cd^AMAL deletion is identical by descent in the Alaskan Malamute and Miniature Australian Shepherd, and has been detected in heterozygosity in the Siberian Husky and Alaskan sled dogs (Yeh 2013). There are no reliable published frequencies for the European German Shorthaired Pointer: limited data.

Breeder management

- Test breeding animals before mating, especially in working lines with exposure to intense light
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier can be mated to a clear animal; offspring intended for breeding must be tested
- Remember the possibility of compound heterozygosity of null (cd^AMAL) and missense (cd^GSPT) alleles in dogs with mixed ancestry with Malamute or Siberian
- Progressively replace carriers with clear offspring without narrowing the gene pool

Specialist notes

The differential diagnosis includes other causes of daytime blindness and of congenital or juvenile blindness. The ophthalmological examination may be normal initially, so the electroretinogram (ERG) is essential: in CD the cones do not respond from the outset, while the rods are preserved for years. Genetic testing allows carriers to be detected before breeding age. A 'clear' CD result does not exclude other forms of PRA or other achromatopsias.

References

1. Sidjanin DJ et al. (2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet 11(16):1823-1833. PMID: 12140185
2. Yeh CY et al. (2013) Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia. BMC Genet 14:27. PMID: 23601474
3. Tanaka N et al. (2014) A cyclic nucleotide-gated channel mutation associated with canine daylight blindness provides insight into a role for the S2 segment tri-Asp motif in channel biogenesis. PLoS One 9(2):e88768. PMID: 24586388
4. OMIA:001365-9615. Achromatopsia-3, CNGB3-related in Canis lupus familiaris. https://omia.org/OMIA001365/9615/

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