Second specific form of Golden Retriever progressive retinal atrophy, of late onset and recessive, caused by a mutation in the TTC8 (BBS8) gene. TTC8 is part of the BBSome complex involved in ciliary membrane biogenesis and photoreceptor function; its loss produces retinal degeneration progressing to blindness. Some affected dogs may show additional signs consistent with a Bardet-Biedl-like phenotype.

Golden Retriever. The exact contribution of TTC8 to PRA in the breed is not well quantified in the sources consulted: limited data. Screen together with prcd-PRA and GR-PRA1.

- Night blindness and progressive loss of vision\n- Progressive retinal degeneration (PRA)\n- Systemic signs consistent with Bardet-Biedl in some dogs (Mäkeläinen et al. 2020)\n- No ocular pain

After the identification of GR_PRA1 and prcd, a proportion of Golden Retriever PRA cases remained unexplained. Downs and colleagues (2014) carried out a new genome-wide association study and mapped a locus on chromosome 8 containing, among others, the TTC8 and SPATA7 genes, both associated with human retinitis pigmentosa. By targeted sequencing they identified a deletion of an adenine in exon 8 of TTC8 (c.669delA) that generates a frameshift and a stop codon, losing the TPR motifs of the carboxy-terminal end. The variant, recessive and with complete penetrance, was named GR_PRA2 and explains around 30% of PRA cases in the breed.

- Test Golden Retriever breeding animals with the TTC8 (GR_PRA2) test before breeding\n- Do not mate two carriers: 25% risk of affected homozygotes\n- A carrier may be mated to a clear animal; offspring intended for breeding must be tested\n- Combine screening with the prcd and GR_PRA1 tests due to the heterogeneity of PRA in the breed\n- Exclude affected animals from breeding

Differential diagnosis with other forms of PRA in the Golden (prcd, GR_PRA1) and with acquired retinopathies. Electroretinography and ophthalmoscopic examination guide the diagnosis; confirmation is molecular. Since TTC8 causes Bardet-Biedl syndrome in humans, in homozygous dogs possible systemic signs (obesity, renal or hormonal alterations) should be monitored, although the canine phenotype appears predominantly retinal.

1. Downs LM et al. 2014, una mutación novel en TTC8 asociada a atrofia progresiva de retina en el Golden retriever (PMID 26401321)
2. Mäkeläinen S et al. 2020, deleción en el gen Bardet-Biedl TTC8 produce degeneración retiniana sindrómica en perros (PMID 32962042)
3. OMIA:001984 PRA GR-PRA2 (TTC8)