Progressive Retinal Atrophy - Crd4/Cord1

Cone-rod dystrophy-PRA is also known as Cord1-PRA. This condition is tested for within the Embark DNA test. There are Clumber Spaniels that have been Embark tested and are confirmed ‘carriers’ and also ‘affected’ with Cord1-PRA and the frequency of the mutation is currently 12% although we here at Clumber Spaniel Health are aware of just 1 dog that has been clinically affected by the condition.

It is a genetic disorder associated with a recessive mutation in the RPGRIP1 gene (Retinitis Pigmentosa GTPase Regulator Interacting Protein 1). This gene codes for an important photoreceptor protein in the eye. This is the gene that must be present on both sides if the DNA for the dog to be affected by PRA-Cord1. This is the gene Embark have reported the mutation on.

There are 1,000+ genes that are active in the eye and over 30 of these are involved in PRA (the generic umbrella) and it is not known how many are specifically involved in PRA-Cord1. There are many types of PRA, but this is the only gene that has been identified, as yet, in the Clumber Spaniel. There is another gene - MAP9 (Microtubule-associated protein 9) that may also contribute to early onset PRA-Cord1 in miniature Dachshunds. This is an incredibly difficult gene to find and it is still uncertain if this is the gene that must also be present to give rise to symptoms of PRA-Cord1.

We should not stop using any lines at this stage but affected dogs should start process of having gene bred out. Breeders should start looking for breeding of clears over next few generations. It is really important to maintain genetic diversity as a reduction in genetic diversity could easily lead to further genetic mutations within the breed.

Cone-rod dystrophy first affects the cones in the retina, which are the photoreceptors responsible for detecting bright light or daylight. Rods, or low-light photoreceptors, begin degenerating secondarily. This leads to a loss of day vision before a loss of night vision. It is highly possible the Clumber Spaniels that are affected may have very subtle changes to their retinas that affect visual acuity and colour vision. Cataracts in older age can also be a secondary symptom of PRA

The age of onset can vary with this disorder. Some dogs (in other breeds) will first begin experiencing problems at around 6 months in age, though the average age of onset is around 5 years of age. A small percentage of dogs do not experience any symptoms until as late as 10 years of age. It is not yet known why some dogs will experience late-onset PRA, however, it is likely due to the presence of other genetic modifiers that have not been determined at this time. (Animal Genetics, UK)

Unfortunately there are no official statistics for how many Clumber Spaniels become clinically affected. Embark are doing further genetic tests to see if the additional gene, MAP9, must be affected in order for PRA signs and symptoms to present at an early age (the modifier). Formen et al, 2016, discussed this when looking at variable age of onset of Retinal Degeneration in Miniature Dachshunds. They discovered further variability in cone electroretinograms (ERGs - a record of the electrical activity of the retina) ranging from normal to absent in an extended RPGRIP1 affected canine colony, irrespective of the MAP9 genotype (present or absent), even within litter mates who were both affected. Often, as in the case of genetics, there is no single gene involved in a particular disease and how it presents. This is highlighted by Das et al, 2017, who concluded that cord1-PRA is a multigenic disease in which mutations in neither RPGRIP1 nor MAP9 alone lead to visual deficits, and additional gene(s) contribute to cone-specific functional and morphologic defects.

PRA has an autosomal recessive mode of inheritance – meaning that a mutated gene has to be inherited from both parents. Both the parents would have to have to carry the mutated gene for it to be expressed in the off spring. Both parents would also have to pass on the other specific required genes for early onset Cord1-PRA. Currently, it is unknown exactly which genes are required to be present or absent. This is a great, clear article on the use of carriers for breeding purposes Cathryn Mellersh - Breeding with Carriers

There are many causes of blindness in dogs and if you suspect that your dog’s eyesight is deteriorating you should contact your vet immediately. Some of the causes of blindness can be treated and vision can be retained. Sadly, other causes like PRA cannot be treated but your vet may be able to help you cope with living with a blind dog.

For more information on EMBARK DNA testing read Here

Resources (Formen et al., 2016) (Das et al., 2017)

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