Novel rare variants found in English Cocker Spaniel with early retinal degeneration

Progressive retinal atrophy (PRA) is a hereditary condition observed in dogs, including the English Cocker Spaniel (ECS) breed, where a recessive variant in PCRD accounts for most of the cases. A male blue roan ECS developed blindness at two years of age. Both parents were tested clear for 26 known variants associated with retinopathies. The retina of both eyes appeared devoid of blood vessels and hyperreflective, leading to the diagnosis of early-onset retinal degeneration. No other clinical signs were detected. The genome of the case and the two parents were sequenced and the polymorphisms, small indels, and large structural variants called compared against the Dog10k database. We found 24 exclusive indels and SNPs. Of these, two were coding variants heterozygous in the parents and homozygous in the case: one AA exchange and one frameshift, both involving genes with a degree of expression in the retina. Additionally, we detected one non-coding exclusive structural variant. This study underscores the complex genetic underpinnings of PRA in ECS, highlighting the potential involvement of novel genetic variants beyond PCRD mutations. Genotyping of a large score of controls is necessary to confirm the segregation of either the exclusive variants with the phenotype. Detection of novel variants is crucial for preserving breed health and assisting breeders confronted with the challenge of producing blind dogs despite their diligent testing efforts.