Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610598 (gene) , 610599 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2006

Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012). The name was updated to include 'PRCD-related' [12/06/2024]

Species-specific symbol: prcd

Mapping: Using the power of comparative mapping, Acland et al. (1998) showed that this disorder in dogs maps to the same location as the gene for retinitis pigmentosa 17 in humans.

Molecular basis: Zangerl et al. (2006) identified a novel gene that they called PRCD in a 106kb candidate region on CFA9. They also showed that "a homozygous mutation (TGC>TAC) in the second codon shows complete concordance with the disorder in 18 different dog breeds/breed varieties tested".

Clinical features: Clinical features of the disease are a result of degeneration of the rods and cones in the eye (Spencer et al., 2016). Dogs are born with normal vision but in adolescence or early adulthood begin to show clinical signs (Miyadera, 2014). The disease typically manifests initially as a lack of coordination in dim light and night blindness (Miyadera, 2014). Affected dogs may also show an aversion to bright lights, difficulty navigating familiar areas and failure to focus on small objects such as balls or toys (Miyadera, 2014). As the cones of the eye degenerate, the night blindness will progress to day blindness (Miyadera, 2012). Ultimately, the disease results in total blindness (Miaydera, 2012). Currently, there is no known cure or treatment for slowing down progression of PRCD. Progression varies between individuals but most dogs become completely blind in 1 – 2 years (Zangerl et al., 2006). [IT thanks DVM student Lauren Alam, who provided the basis of this contribution in April 2022]

Pathology: The PRCD protein is bound to discs in the outer segments of rods and cones (Spencer et al., 2016; Allon et al., 2019). The PRCD protein is essential for long-term photoreceptor viability (Spencer et al., 2019). In PRCD disease, the protein is mislocalised from the outer segment discs (Spencer et al., 2016). In early disease about 40% reduction in rod disc renewal is seen, and the visual cells of the posterior pole and equatorial regions of the eye demonstrate vesicular appearances and outer segment lamellar disorientation (Aguirre et al., 1982; Spencer et al., 2019). As the disease progresses, all photoreceptor outer segments display changes including misoriented discs, subretinal invasion of phagocytic cells and extracellular vesicles (Spencer et al., 2019). Outer segments are eventually lost entirely (Spencer et al., 2019). [IT thanks DVM student Lauren Alam, who provided the basis of this contribution in April 2022]

Prevalence: Lewis and Mellersh (2019) reported a decline in frequency of the PRCD:c.5G>A variant in Labrador Retrievers from 0.078 (7.8%) prior to publication of the variant, to 0.003 (0.3%) 8-10 years after publication of the variant. This represents a 96.5% decline in frequency of the variant as a result of testing. For the same variant in English Cocker Spaniels, the equivalent results were a decline in frequency from 0.126 (12.6%) to 0.006 (0.6%) 8-10 years after publication of the variant, which represents a decline in frequency of 95.1% as a result of testing. Andrade et al. (2019) reported the frequency of this same variant in English Cocker Spaniels in Brazil: "220 ECS dogs was used for genotyping, of which 131 were registered from 18 different kennels and 89 were unregistered. . . . The . . .[PRCD:c.5G>A] allele frequency was 25.5%. Among the registered dogs, the allele frequency was 14.9%; among the dogs with no history of registration, the allele frequency was 41%." Clark et al. (2023) "utilized a large set of genotypes from dogs tested for the progressive rod-cone degeneration–progressive retinal atrophy (prcd-PRA) G>A missense PRCD variant (n = 86,667) and the collie eye anomaly (CEA)-associated NHEJ1 deletion (n = 33,834) ... . ... Forty-one breeds and breed mixes in our prcd-PRA dataset were genotyped for having at least one copy of the PRCD variant ... . Regression modeling showed time progression to significantly affect the odds of a dog being homozygous or heterozygous for either disease, as do variables including breed and breed popularity. This study shows that genetic testing informed breeding decisions to produce fewer affected dogs. However, the presence of dogs homozygous for the disease variant, especially for prcd-PRA, was still observed fourteen years after test availability, potentially due to crosses of unknown carriers."

Breeds: American Cocker Spaniel (Dog) (VBO_0200038), American Eskimo Dog (Dog) (VBO_0200046), Australian Cattle Dog (Dog) (VBO_0200088), Australian Shepherd (Dog) (VBO_0200095), Australian Stumpy Tail Cattle Dog (Dog) (VBO_0200097), Barbet (Dog) (VBO_0200119), Chesapeake Bay Retriever (Dog) (VBO_0200326), Chihuahua (Dog) (VBO_0200338), Chinese Crested (Dog) (VBO_0200345), Cockapoo (Dog) (VBO_0200370), English Cocker Spaniel (Dog) (VBO_0200486), Entlebucher Mountain Dog (Dog) (VBO_0200503), Finnish Lapphund (Dog) (VBO_0200523), Golden Retriever (Dog) (VBO_0200610), Goldendoodle (Dog) (VBO_0200611), Karelian Bear Dog (Dog) (VBO_0200754), Kuvasz (Dog) (VBO_0200793), Labradoodle (Dog) (VBO_0200798), Labrador Retriever (Dog) (VBO_0200800), Lapponian Herder (Dog) (VBO_0200814), Norwegian Elkhound (Dog) (VBO_0200955), Nova Scotia Duck Tolling Retriever (Dog) (VBO_0200964), Poodle (Dog) (VBO_0201048), Poodle, Miniature (Dog) (VBO_0201051), Poodle, Toy (Dog) (VBO_0201061), Portuguese Podengo (Dog) (VBO_0201067), Portuguese Water Dog (Dog) (VBO_0201077), Schipperke (Dog) (VBO_0201184), Silky Terrier (Dog) (VBO_0201237), Spanish Water Dog (Dog) (VBO_0201280), Swedish Lapphund (Dog) (VBO_0201315), Swedish White Elkhound (Dog) (VBO_0201317), Yorkshire Terrier (Dog) (VBO_0201448).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: