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eo-PRA (early-onset progressive retinal atrophy) — Portuguese Water Dog

Ocular · Dog

Early-onset progressive retinal atrophy (PRA) described in the Portuguese Water Dog, with progressive degeneration of photoreceptors leading to blindness. It is a form molecularly distinct from the late-onset prcd-PRA (PRCD gene) that also affects this breed. The Schapendoes presents another variant of the same CCDC66 gene causing a generalised PRA. There is no published evidence of this variant in the Spanish Water Dog.
Inheritance patternAutosomal recessive. In the Portuguese Water Dog the pedigree analysis suggested autosomal recessive inheritance and obligate heterozygous carriers were identified.
Gene / MutationCCDC66 (CFA20): 1 bp insertion (CFA20:g.33.717.704_33.717.705insT, CanFam3.1; c.2262_c.2263insA; p.Val747SerfsTer8), with perfect cosegregation with the disease. Distinct from the prcd variant (PRCD c.5G>A) of late-onset PRA.
PenetranceHigh in homozygotes; heterozygotes are carriers without signs. No penetrance modifiers have been described in this form.
Codehder
Turnaround time7 days
Price52,60 €

Incidence

Form validated in the Portuguese Water Dog, with onset at 2-3 years. The Schapendoes presents another CCDC66 variant (generalised PRA). There is no published evidence of this variant in the Spanish Water Dog.

Breeder management

- Test breeding animals with the genetic test available for the breed (CCDC66 and PRCD)
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier can be mated with a free animal; offspring intended for breeding must be tested
- Exclude affected animals from breeding
- Annual ophthalmological examination of breeding animals and pedigree recording
- Distinguish in genetic counselling eo-PRA (CCDC66) from prcd-PRA (PRCD), due to their different molecular basis and age of onset

Specialist notes

Differential diagnosis with other PRAs (prcd-PRA, cone-rod dystrophy) and with cataracts. Electroretinography characterises the cone-rod pattern. It is important to distinguish the early form (eo-PRA, CCDC66, onset 2-3 years) from the late prcd-PRA (PRCD, onset 3-6 years or more) of the Portuguese Water Dog, since their molecular basis and reproductive management differ. There is no treatment; management is palliative and involves adapting the animal.

References

1. Murgiano L, Becker D, Spector C, et al. CCDC66 frameshift variant associated with a new form of early-onset progressive retinal atrophy in Portuguese Water Dogs. Sci Rep. 2020;10(1):21162. PMID: 33273526
2. Zangerl B, Goldstein O, Philp AR, et al. Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans. Genomics. 2006;88(5):551-563. PMID: 16938425
3. Dekomien G, Vollmer C, Petrasch-Parwez E, et al. Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene. Neurogenetics. 2010;11(2):163-174. PMID: 19777273

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