Cone-Rod Dystrophy 1 (PDE6B gene)

Cone and rod dystrophies (CRD) affect the retinal photoreceptor cells, cones and rods, resulting in reduced visual acuity followed by severe vision loss that often progresses to total blindness.

Symptoms

Symptoms of CRD can appear between the ages of 1 and 4 years and include pupils that are smaller than normal in size, early retinal changes and, in later stages, generalized bilateral retinal atrophy. The pathology can be detected with fundus examination to evaluate the retina and electroretinography. In cone-rod dystrophy 1 the onset of symptoms is early, retinal degeneration can be observed at a few months of age.

Disease Management

There is no treatment for progressive vision loss. Thanks to their acute senses of smell and hearing, dogs can compensate for this loss, especially in familiar environments. You can help your dog by establishing regular exercise routes and gradually introducing the necessary changes.

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

The photoreceptor cells of the retina, cones and rods, receive light stimuli from the environment and transmit the information to the brain, where it is interpreted and converted into vision. When the photoreceptor cells lose their function, a gradual loss of vision occurs, which can eventually lead to blindness. In dogs, more than 100 different breeds can have some form of inherited retinal degeneration that usually affects the cones, with or without involvement of the rods. Related mutations have been described in more than 200 genes, reflecting the great phenotypic heterogeneity. Goldstein et al. identified retinal disorders with autosomal recessive inheritance in two different breeds, the American Staffordshire Terrier and the American Pit Bull Terrier. In both, the onset of the disease was early, before the age of one year, and resulted in severe photopic (ability to discriminate colors) and scotopic (ability to discriminate between whites, blacks and shadows) visual impairment, which progressed to more severe blindness in early adulthood. Both pathologies were named cone-rod dystrophy 1 (crd1) and cone-rod dystrophy 2 (crd2), respectively. In the case of crd1, it is caused by mutations in PDE6B which codes for one of the three subunits that compose the PDE6 protein that is essential in the visual signaling cascade. Here we analyzed the presence/absence of the crd1-related deletion c.2404_2406del in American Staffordshire Terrier dogs.

Most affected breeds

American Staffordshire Terrier

Bibliography

Goldstein O, Mezey JG, Schweitzer PA,et al. IQCB1 and PDE6B mutations cause similar early onset retinal degenerations in two closely related terrier dog breeds. Invest Ophthalmol Vis Sci. 2013 Oct 25;54(10):7005-19.