Achromatopsia-2 (CNGA3 gene, German Shepherd )

Achromatopsia is an autosomal recessive disease that causes the photoreceptor cells of the retina, known as cones, to not function properly, although they remain intact, causing daytime blindness. Achromatopsia can be caused by alterations in several genes, but one of the main causes is the presence of alterations in the CNGA3 and CNGB3 genes.

Symptoms

The first symptoms appear between 8 and 12 weeks, by which time the puppies have developed vision. In bright light the puppies are practically blind and tend to move away to dimly lit areas, which is known as photophobia. There is a loss of function of the retinal cones, but ophthalmologically the dogs are normal. The degeneration does not affect the rods, so vision in low light is normal.

Disease Management

In case your dog shows any symptoms you should see your veterinarian for evaluation. Loss of cone function can be detected by electroretinography. Verbal signals can be used instead of visual hand signals. Gradually accustoming your dog to his environment (e.g., walking him in low light) will help him become more confident during bright times of the day. It is also advisable to keep your dog on a leash and harness, as this can be supportive.

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

Achromatopsia, day blindness or cone degeneration may be caused by the presence of mutations in the CNGA3 and CNGB3 genes involved in phototransduction. Both genes encode for subunits of signal transduction ion channels in retinal sensory neurons. These channels are located in the cell membrane and regulate the passage of cations. In the CNGA3 gene, a large deletion typical of the Labrador Retriever and the c.1270C>T mutation (discussed here) typical of the German Shepherd occur naturally, both of which have been associated with achromatopsia. Tanaka et al. observed that the c.1270C>T variant produces a conformational change in the encoding channel protein and causes the channel to remain closed thereby suppressing the ability to transmit signals from the retinal cones.

Most affected breeds

German Shepherd Dog
Labrador Retriever

Bibliography

Tanaka N, Dutrow EV, Miyadera K,et al. Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment. PLoS One. 2015 Sep 25;10(9):e0138943.