Rod-Cone Dysplasia 3 (PDE6A gene)

Cone and rod dysplasia type 3 (CRD3) is an eye disease caused by a mutation in the PDE6A gene, which is involved in the development of the photoreceptor cells of the retina. This type of retinal dysplasia is most common in dogs of the Cardigan Welsh Corgi breed.

Symptoms

Puppies with CRD3 usually show signs of vision loss from the first few weeks of life and symptoms progress rapidly until blindness occurs at approximately one year of age.

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. CRD3 is caused by mutations in the PDE6A gene, which encodes for the alpha subunit of phosphodiesterase, an enzyme composed of three subunits located in the cell membrane of photoreceptors where it participates in the phototransduction cascade. Here we study the variant c.1847del, identified by Petersen-Jones et al. in Cardigan Welsh Corgi dogs with CRD3, which produces a single nucleotide deletion in the PDE6A gene sequence.

Most affected breeds

Cardigan Welsh Corgi

Bibliography

Petersen-Jones SM, Entz DD, Sargan DR. cGMP phosphodiesterase-alpha mutation causes progressive retinal atrophy in the Cardigan Welsh corgi dog. Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1637-44.

Petersen-Jones SM, Zhu FX. Development and use of a polymerase chain reaction-based diagnostic test for the causal mutation of progressive retinal atrophy in Cardigan Welsh Corgis. Am J Vet Res. 2000 Jul;61(7):844-6.