Early onset Progressive retinal atrophy in Portuguese water dogs

The PRA disease, progressive retinal atrophy, is manifested by the gradual degeneration of the light-sensitive retinal cells. According to various criteria (age and rate of onset, type of retinal cell degeneration, mode of degeneration, genetic background, affected breed), several types of PRA are distinguished.

In the Portuguese Water Dog breed, a PRCD variant has been identified in the past, which is the basis for late-onset PRA. However, an early onset variant (EO PRA) is also known in which clinical signs begin to appear as early as between 2 and 3 years of age. This variant is caused by a mutation in the CCDC66 gene, which has a role in the proper function and maintenance of retinal viability. It is a 1bp insertion (c.2262_c.2263insA) that causes a reading frame shift and premature insertion of the stop codon and therefore truncation of the resulting protein.

The disease manifests itself with progressively worsening vision, both in dim light and in good light conditions. Tracking of moving objects is also difficult. In affected dogs, ophthalmoscopic changes such as tapetal hyperreflectivity, diffuse vascular attenuation, optic disc pallor, and multifocal depigmentation in the non-tapetal fundus are gradually observed.

The disease affects dogs with P/P (positive / positive) genotype only. Dogs with P/N (positive /negative) genotype are clinically without any symptoms. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended. DNA test is based on multiplex PCR and makes it possible to find out possible deletion and to determine possible carriers.

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Reference:

Murgiano, L., Becker, D., Spector, C., Carlin, K., Santana, E., Niggel, J.K., Jagannathan, V., Leeb, T., Pearce-Kelling, S., Aguirre, G.D., Miyadera, K. : CCDC66 frameshift variant associated with a new form of early-onset progressive retinal atrophy in Portuguese Water Dogs. Sci Rep 10:21162, 2020. Pubmed reference: 33273526. DOI: 10.1038/s41598-020-77980-5.