Cerebellar Degeneration or CA

Cerebellar Degeneration CD, also referred to as Cerebellar Cortical Abiotrophy CCA, or Cerebellar Ataxia CA, is a hereditary neurological disease in the Gordon Setter breed. It is a slowly progressive neuromuscular incoordination caused by a simple autosomal recessive gene. Clinical signs can be recognized between six months to four years of age. Pathology studies performed in the 1970s show the age of onset closer to six months; but with mild clinical signs affected dogs may not be identified until later in life.

Clinical signs include: poor balance, frequent stumbling, a wide-based stance, head and/or body tremors, and a high-stepping gait. Affected dogs have normal mental alertness. Most affected dogs have a normal life expectancy and pass away from unrelated causes. There is no treatment or cure. CD is not related to the lethal metabolic encephalopathy (DUNG’d) seen in 3 to 6 week old Gordon Setters.

Drs. Alexander de Lahunta, Linda Cork, and Steven Steinberg identified the autosomal recessive mode of inheritance of CD in the breed and published its clinical description in several articles in the early 1980s. With this mode of inheritance, both parents must be carriers of the mutated gene to produce affected offspring. Approximately one-quarter of offspring from such matings are expected to be affected, but statistical chance can cause none to several affected dogs in a litter.

In 2012, Dr. Natasha Olby at North Carolina State University identified the mutated gene. A cheek swab test is available that will determine your dog’s genetic status as normal, carrier, or affected for CD. The test is available for any Gordon Setter worldwide through North Carolina State University (http://www.cvm.ncsu.edu/vhc/csds/vcgl/). It can be run at any age and costs $51(US) per test.

Gordon Setters affected with CD have been identified since at least the 1960s in both conformation and field lines throughout the United States, Canada, Europe, and Australia. Pedigrees of affected and carrier Gordon Setters worldwide do not “connect” before generationally early ancestors of the breed. All confirmed affected Gordon Setters around the world have the same identified mutated gene causing CD. Dr. Olby also identified this mutation as the cause of CD in the Old English Sheepdog breed – showing a common ancestor as the original source of the mutation in both breeds. No other breeds have been identified with the same mutation to date.

Over the years, Gordon Setter breeders and owners have been surprised by a diagnosis of CD in their dogs due to the lack of known relatives with the disorder. Historically, these occurrences are followed by more affected dogs from related lines. The ancient ancestral origin of the mutated gene explains this occurrence. The mutated gene has been dispersed and propagated in the Gordon Setter breed since its origination. Now that there is an inexpensive and accurate genetic test for the mutated gene, ALL breeding stock should be tested.

As with all testable simple autosomal recessive genes, quality carrier dogs can be bred to quality normal-testing mates. This prevents CD affected dogs from being produced while preserving and maintaining other positive traits. Quality normal-testing offspring should replace the carrier parent for breeding. Carrier offspring should be selected against for breeding homes. In this way, you have eliminated the single mutated gene, without losing the quality traits of the line. A genetic test for a simple recessive disorder should not change who gets bred, only who they get bred to.

To assist breeders with health-conscious breeding, each dog’s results should be entered into the OFA Cerebellar Degeneration registry (http://www.offa.org/pdf/dnaapp_bw.pdf). The test results will be listed on the dog’s OFA page. The cost is $15 per dog, $30 for a litter of 3 or more, and a kennel rate of $7.50 per dog if 5 or more dogs are entered by the same owner (all in $US). If a dog is out of two DNA tested normal Gordon Setter parents, the OFA will provide Clear by Parentage (CBP) certification. In this way, generations of Gordon Setters do not have to be tested. CBP certification requires that both parents are CD tested and entered into the OFA registry, and that the parents and offspring have been DNA parentage certified (usually available through your national Kennel Club).

Cerebellar Degeneration is not the most frequent genetic disorder affecting the breed, but is the oldest documented simple inherited disorder in Gordon Setters. With the availability of this accurate and inexpensive genetic test Gordon Setters should never again be affected with Cerebellar Degeneration.

This article can be reprinted with permission from the author Jerold S Bell DVM, Tufts Cummings School of Veterinary Medicine, N. Grafton, MA USA jerold.bell@tufts.edu


Progressive Retinal Atrophy or PRA 

Identification of Mutation for Progressive Retinal Atrophy in the Gordon Setter

A mutation responsible for the development of Progressive Retinal Atrophy (PRA) in the Gordon Setter has been identified by geneticists working in the Kennel Club Genetics Centre at the Animal Health Trust.

PRA is a well-recognised inherited condition that many breeds of dog are predisposed to. The condition is characterised by bilateral degeneration of the retina which causes progressive vision loss that culminates in total blindness. There is no treatment for PRA.

Owners report that their affected dogs develop night blindness in the first instance, which is indicative of a rod-cone degeneration, so we have termed this mutation rcd4 (for rod-cone degeneration 4) to distinguish it from other, previously described, forms of rod-cone degeneration.

The mutation is recessive and 19 out of the 21 Gordon Setters in our study that had clinical signs of PRA were homozygous (carried two copies) for this mutation, indicating it is the major cause of PRA in the breed. Two dogs in our study had PRA but did not carry the rcd4 mutation, indicating there might be another, genetically distinct, rarer form of PRA segregating in this breed.

The Animal Health Trust has developed a DNA test for the rcd4 mutation that will be available from Monday 14th March, 2011. DNA test kits will be available to order online, via our website (www.aht.org.uk) from March 14th. The price of the test will be £48 per sample, which includes VAT.

The research that led to identification of the rcd4 mutation was funded by many different organisations, including the Kennel Club Charitable Trust, the British Gordon Setter Club, the Gordon Setter Field Trial Society, the Gordon Setter Association, the Gordon Setter Club of Scotland and the LUPA project (www.eurolupa.org.uk) as well as several individuals who have also contributed significantly. The AHT would like to thank sincerely all the organisations and individuals who donated funds to help support the research as well as all the owners who contributed DNA and information from their dogs.

Table showing all the combinations of outcomes for different matings