Rod-Cone Dysplasia 1 (PDE6B gene)

Cone and rod dysplasia type 1 (CRD1) is an eye disease caused by a mutation in the PDE6B gene, which is crucial for the normal function of photoreceptor cells (cones and rods) in the retina.

Symptoms

Dogs with CRD1 usually show signs of vision loss at an early age, often between 4 weeks and the first year of life. At first, dogs may have difficulty seeing in low light conditions, known as night blindness, but as the disease progresses, daytime vision loss occurs.

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, resulting in a progressive loss of vision that evolves rapidly over the first few months of life. Retinal dysplasia can have a genetic origin, but it can also be acquired and due to other factors such as a viral infection. CRD1 is caused by mutations in the PDE6B gene, which codes for the beta subunit of phosphodiesterase, an enzyme of the photoreceptor cell membrane that is crucial for its participation in the phototransduction cascade. Specifically, here we analyze the c.2421G>A mutation that produces a premature stop codon and a truncated protein lacking the C-terminal end necessary for its correct localization in the photoreceptor membrane. This condition occurs in some breeds and is most common in Irish Setters.

Most affected breeds

Irish Setter

Bibliography

Suber ML, Pittler SJ, Qin N,et al. Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3968-72.