Progressive retinal atrophy in Golden Retriever and Labrador Retriever (GR-PRA2)

Nowadays, there are known many mutations causing progressive retinal atrophy in many dog breeds.  Particularly in Golden Retrievers, this disease can be caused by mutations in three distinct genes.   Earlier, this disease was associated with prcd-PRA mutation that occurs quite often and causes retinal atrophy in more than 29 breeds. Then, a mutation in SLC4A3 gene, known as GR-PRA1, was identified. However, it was a mystery why dogs that have been already tested and dominant homozygous for PRCD and GR-PRA1 and should therefore not be affected by this disease, have suffered from the progressive atrophy.  This mystery surrounding the seemingly healthy dogs has not been cleared until the mutation TTC8 causing GR-PRA2 was identified.

GR-PRA2 is a severe disease caused by one base deletion in TTC8 gene (c.699delA). This deletion shifts the reading frame leading to creation of premature stop codon.  The retinal atrophy develops in dogs at higher age (5years). The disease is characterized by the degeneration of the retina causing progressive vision loss leading to complete blindness.

GR-PRA2 is a recessively inherited disease. The disease develops in dogs which inherit the mutated gene from each parent.  These dogs are designated as P/P (positive/positive). The carriers of the mutated gene are designated as N/P (negative/positive). The carriers inherited the mutated gene from one parent only and are without clinical signs. However, they pass the disease on to their offspring.  When mating two heterozygotes (N/P), there will be theoretically 25% of the offspring healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will be affected by GR-PRA2.  Mating one healthy dog (N/N) with a carrier of this mutation (N/P) will theoretically produce 50% carriers and 50% healthy offspring.  If a carrier (N/P) is mated with an affected dog (P/P), there will be theoretically 50% affected dogs and 50% carriers.

If there is a reason to believe that the dog can suffer from retinal atrophy, it is recommended that the dogs are tested for GR-PRA2 together with GR-PRA1 and PRA-prcd. It is highly probable that other mutation responsible for this disease will be discovered in future. Although the most cases of PRA have been explained by genetic testing, there always occur dogs in which the retinal atrophy was diagnosed in spite of the fact that according to the genetic examination for PRA-prcd, GR-PRA1 and GR-PRA 2 the dogs should be negative for this disease.

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References:

Downs, Louise M., et al. "A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever." Canine Genetics and Epidemiology 1.1 (2014): 1.

Downs, Louise M., et al. "Genetic screening for PRA‐associated mutations in multiple dog breeds shows that PRA is heterogeneous within and between breeds." Veterinary ophthalmology 17.2 (2014): 126-130.