Progressive Retinal Atrophy (CORD1 type)

Find out if your Miniature Dachshund or English Springer Spaniel could develop CORD1 Progressive retinal atrophy at CAGT.

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Overview

Progressive retinal atrophy (PRA) is the most common form of inherited disease affecting the retina in dogs. Genetically different forms of PRA, caused by mutations in different genes, affect many breeds of dog with each form usually affecting one or a small number of breeds. PRA is characterised by progressive degeneration of the retina at the back of the eye and leads to vision loss and blindness.

In most knowns forms of PRA the rod cells of the retina degenerate first, resulting in a loss of dim light vision initially. In this specific form of PRA the cone cells of the retina degenerate first, followed by the rod cells (cone rod dystrophy), so dogs affected with CORD1 do not develop night blindless first. As with all dogs suffering from PRA, there is no cure. Dogs generally adapt quite well to blindness – especially when it develops gradually – as long as their surroundings remain familiar (e.g. furniture does not get rearranged, they do not move house etc).

The age of onset of CORD1 is highly variable. Dogs the are also homozygous for the MAP9 modifier mutation will develop the disease from a young age (< 3 years old). On the other hand, dogs that are homozygous for the CORD1-RPGRIP1 variant but not the MAP9 variant may develop the disease later in life (> 6 years old).

Autosomal Recessive

The insertion in the gene called RPGRIP1 that causes cone rod degeneration (CORD1) in many breeds is recessive. This means that dogs that carry two copies of the mutation (homozygotes) will almost certainly develop CORD1 during their lives. Dogs that carry a single copy of the mutation (also known as carriers or heterozygotes) will not develop CORD1 as a result of the RPGRIP1 mutation, but they will pass the mutation onto about half of any offspring they have. Breeding dogs that will not develop CORD1 should be the breeder’s priority, with a reduction in mutation frequency within the whole breed being the secondary, longer-term target.

Carriers can be bred from safely, provided they are mated to a dog that has also been tested and is clear of the RPGRIP1 mutation (i.e. carry no copies of the mutation). If a carrier is mated to a clear dog approximately half of the resulting puppies will also be carriers, so should be tested themselves prior to breeding. Breeding carriers to tested, clear dogs is safe, in terms of avoiding dogs affected with CORD1, and will help to maintain the genetic diversity of a breed. It is therefore encouraged, particularly in the first few generations following the availability of a new genetic test, so that other desirable characteristics and traits can be preserved before the frequency of the disease mutation within the breed is gradually reduced.

Gene RPGRIP1
Variant Insertion c.338-339InsA(29)GGAAGCAACAGGATG p.Thr59STOP
Assay Type Variant Specific
Inheritance Autosomal Recessive
Severity Low-Moderate: Affected animals experience discomfort or dysfunction of some kind, but life expectancy is not affected.
Publication

Mellersh CS, Boursnell ME, Pettitt L, et al. (2006) Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics. 88(3): 293-301. DOI: 10.1016/j.ygeno.2006.05.004.

Miyadera K, Kato K, Boursnell M, et al. (2012) Genome-wide association study in RPGRIP1(-/-) dogs identifies a modifier locus that determines the onset of retinal degeneration. Mamm Genome. 23(1-2): 212-223. DOI: 10.1007/s00335-011-9384-9.

Forman OP, Hitti RJ, Boursnell M, et al. (2016) Canine genome assembly correction facilitates identification of a MAP9 deletion as a potential age of onset modifier for RPGRIP1-associated canine retinal degeneration. Mamm Genome. 27(5-6): 237-245. DOI: 10.1007/s00335-016-9627-x.