Retinal atrophy, progressive, generalized (gPRA) and early (EOPRA)

Gene: CCDC66

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Schapendoes mutation: Insertion, CCDC66 gene; c.521 ins.A, p.(N174K fs STOP 2), exon6

Spanish Water Dog mutation (EOPRA allele): Insertion, CCDC66 gene; c.2262 ins.A, p.(V747S fs STOP 8)

Medical system: Ocular

Breeds : Portuguese Water Dog, Schapendoes

Age of onset of clinical signs: Between two and five years of age in Schapendoes (PRA-Generalized); around two years of age in Portuguese Water Dogs (EOPRA).

Progressive retinal atrophy is a disease that causes progressive degeneration of the retina’s photoreceptor cells. Rod photoreceptors, responsible for night and peripheral vision, are affected first, resulting in loss of night vision. Eventually, the cone photoreceptors, responsible for daylight and color vision, are also affected, leading to complete blindness. The disease generally affects both eyes, with the age of onset of symptoms highly variable. For the EOPRA allele (for “Early-Onset PRA”) seen in the Portuguese Water Dog, the age of onset of clinical signs is around two years.

References:

OMIA link: [1521-9615]

Genetics Committee of the American College of Veterinary Ophthalmologists. (2021) The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition.  [https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf]

Murgiano L, Becker D, Spector C, et al. (2020) CCDC66 frameshift variant associated with a new form of early-onset progressive retinal atrophy in Portuguese Water Dogs. Sci Rep 10:21162.  [pubmed/33273526]

Palanova A. (2016) The genetics of inherited retinal disorders in dogs: implications for diagnosis and management.  Vet Med (Auckl). 7:41-51. [pubmed/30050836]

Dekomien G, Vollrath C, Petrasch-Parwez E, et al. (2010) Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene.  Neurogenetics 11:163-174. [pubmed/19777273]