Cone and Rod Dysplasia 4 (PCARE gene)

Cone-rod dysplasia type 4 (CRD4) is an eye disease caused by a mutation in the PCARE gene, which is widely expressed in the photoreceptor cells (cones and rods) of the retina.

Symptoms

Dogs with CRD4 usually show clinical signs at middle to late age (5-12 years), with slow clinical progression. Fundus changes may occur including hyperreflectivity of the tapetum (a layer of tissue that helps improve night vision) along with vascular problems and pigmentary changes. Early symptoms include night blindness due to rod degeneration. As the disease progresses, daytime vision loss also occurs due to cone degeneration, which can eventually result in blindness.

Disease Management

Unfortunately, there is no cure for cone and rod dysplasia. Management of the disease focuses on helping dogs adapt to their vision loss, which may include teaching them to respond to auditory cues and modifying their environment to make it safe. If your dog shows any symptoms, you should see your veterinarian for an evaluation.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Cones and rods are the cells in the retina that detect external light and transmit the information to the brain, where it is interpreted into vision. Cones are responsible for color vision and fine detail in bright light, while rods are involved in vision in low light conditions. In cone and rod dysplasia, both cells are affected. Retinal dysplasia can have a genetic origin, but it can also be acquired and due to other factors such as, for example, a viral infection. The PCARE gene, also known as C2orf71, encodes a protein whose function is still under investigation, although it is known to be widely expressed in the human eye and localized in the outer segment of the photoreceptors. In our study, we have examined a specific variant in the PCARE gene that involves the insertion of a single base (c.3149_3150insC), resulting in the introduction of a premature termination codon. As a consequence, a truncated protein is formed that lacks 171 residues at its C-terminal end. This variant was described in the study by Downs et al. where it was estimated that, for the Gordon Setter and Irish Setter breeds, other mutations may also be involved in the development of CRD4.

Most affected breeds

Gordon Setter
Irish Setter
Ancient Danish Pointing Dog
Polish Shepherd Dog of the Plains
Polish Shepherd Dog of Podhale
Paniche
Miniature Poodle
Tibetan Terrier

Bibliography

Downs LM, Bell JS, Freeman J, et al. Late-onset progressive retinal atrophy in the Gordon and Irish Setter breeds is associated with a frameshift mutation in C2orf71. Anim Genet. 2013 Apr;44(2):169-77.