Progressive Retinal Atrophy (PRA)

* * Please also see the Breed Council webpage under Organisations * *

Wendy Smith's report has been endorsed by Dr Malcolm Willis and Dr Cathryn Mellersh (AHT UK). It has been sent to the breeders and owners of the Gordon Setters implicated. It has also gone to all the Gordon Breed Clubs in the UK. Please also read the Gordon Setter Breed Councils Statement.

LIVING IN THE DARK

Progressive retinal atrophy (PRA) is the collective term for a group of inherited diseases of the retina, all of which are incurable and invariably lead to total blindness. PRA is known to affect many breeds of dog and characteristics such as the age at which with the disease progresses can vary from breed to breed. In some breeds the age of onset is very early but with other breeds, dogs may not start to go blind until they are well into middle age, or even older. Unfortunately, it is a late onset form of PRA that our lovely breed appears to suffer from.

Some of the members of the committee will remember Kewstoke Apprentice in the show ring as a total extrovert and a real handful for me. Apart from his blindness he is still a totally fit and healthy dog. His degree of vision now is zero, a year ago it was moving shadows, now even in the brightest sunlight he walks into every obstacle.

It was two years ago that I realised that there was definitely a problem with Will’s eyesight, he was then eight years old. Up until then I had been unaware that the disease PRA was such an issue in dogs. Interestingly, he had been eye tested at Crufts in his youth of course there had been no indication then. A copy of one of his clear eye tests taken when he was 5 years old is attached.

The initial symptoms were unwillingness to go outside at dusk or night and unusually for him, panic when faced with a dim situation on a walk, heavy shading in woodland would spook him. He simply refused to walk in places like that.

I made a decision in 2005 to leave the UK and live in France and later Portugal. In May 2008 I returned to the UK and with a referral took Will to see Mr. Paul J. Evans, MA, VetMB, CertVOpthal, MRCVS at his Veterinary Eye Hospital in Leominster. I was full of hope that I would be able to help my lovely boy to regain his sight, how disappointing to learn the facts. A copy of his report is attached. Total blindness was inevitable and we must learn to live with it. Then the real issue for me was to compile all available information, so that as a group the Gordon Setter fraternity are no longer ignorant of the facts.

The only thing I can do is tell the committees of our breed clubs, the Breed Council and with your permission to go public so that every single member of the British Gordon Setter Club, Gordon Setter Association, Gordon Setter Club of Scotland and Field Trial Society is made aware of this debilitating disease. More importantly though to help each person involved in dogs to understand how with joint effort this problem can be avoided. Sharing knowledge is our ally. I have researched thoroughly, the following information has been verified by Dr Malcolm Willis, well recognised for his work in genetics and my thanks also go to Dr. Cathryn Mellersh from the Animal Health Trust for her guidance.

Dr. Willis made a couple of suggestions which are:-

To record dogs ID with the blood samples

To circulate this report immediately to members of all UK Gordon Setter organisations, clubs, societies.

For the breed clubs and societies to recommend that the advice given in this report be acted upon by members in regard to tracing and collecting blood samples of affected dogs.

As responsible breeders it has become second nature to us to screen for HD with the BVA hip dysplasia scheme, which has resulted in the average hip score now much improved since it became one of the breed clubs’ code of ethics. Latterly, many also consider it important to gene test for the liver pigment.

To date several genetic mutations have been identified that cause PRA in different breeds. It is important to understand that there are different forms of PRA and PRA in different breeds can be caused by different genetic mutations. The mutation causing the PRA in the Gordon Setter is not one previously identified in other breeds, I have received advice from Optigen regarding the Kewstoke Apprentice blood sample, there is no similarity with any other genetic mutation already available in a DNA test. Which is a great pity for us all, as much time would have been saved in the search for a DNA test for the Gordon Setter. The American company ‘Optigen’ will (free of charge) test a blood sample from any affected (blind) dog, to forward their research for a gene test. www.optigen.com Closer to home the Animal Health Trust also does extensive research into genetic disorders and they too will help with trying to locate the mutation responsible. All that is needed in the first instance, is for owners that have a dog that they are concerned can’t see as well as it should, to have a canine ophthalmologist confirm that it is PRA, then submit a blood sample (preferred) or if not, then a cheek swab to the AHT. Donating a sample is free and all information kept in the strictest confidence. For active research to begin it will be necessary to collect samples from at least twelve affected dogs, these samples can be collected over time and will be safely stored by the AHT & Optigen until sufficient have been collected. This number would give the genetic researchers enough material to start work on identifying the mutation responsible for PRA in the Gordon Setter. Blood samples from siblings or offspring of the affected dogs are also necessary. Finally, samples will also be needed from unaffected dogs. Because PRA is probably a late onset condition in this breed, unaffected dogs should have had a clear eye examination over the age of 10 years.

Once a gene test is available, then all puppies simply have the gene test to verify their genetic status. The carriers can still be used in a breeding programme so long as they are only ever mated with a DNA tested clear dog. That way breeding blind dogs is avoided, and dogs which have many other excellent attributes are still kept in the gene pool. Gradually the disease will be eliminated, as we endeavour to keep the clear dogs and use the KC registration endorsement to protect the future Gordons. Our breed clubs can introduce this into the Code of Ethics in the same way that the BVA/HD scoring came into practice.

Some members are under the misapprehension that a simple eye test with the vet will tell them that their dog doesn't’t have PRA, I hope that the following information will explain the disease more clearly.

PRA is usually caused by an autosomal recessive mutation. This means that a dog must inherit two copies of the mutation, one from its sire and one from its dam for it to be affected. It also means that both parents of an affected dog must be carriers. If a dog inherits a single copy of the causal mutation from either of its parents and a normal copy of the same gene from the other parent then it will be a carrier: it will never develop PRA during its lifetime but will pass the mutation on to approximately half its offspring.

If the dog inherits two copies of the mutation it will develop PRA, but its eyes will be healthy until it reaches the ‘age of onset’ and clinical signs begin to develop. If an ophthalmologist examines a genetically affected dog before it begins to display clinical signs he/she will not be able to tell if the dog is affected and the dog will receive a clear eye certificate. An ophthalmologist can only tell a dog is genetically affected once the clinical signs of PRA have begun to develop. Then to further confuse us, secondary cataracts can also develop, frequently the local vet will attribute the early blindness to cataracts and the real cause is overlooked.

There are various scenarios for transmission, which given the limited gene pool for the British Gordon Setter increases the odds of the disease occurring. Two thirds of canine genetic disorders are recessive.

To explain this inheritance pattern ~

GREEN DOGS - CLEAR

YELLOW DOGS - CARRIER

RED DOGS - AFFECTED

RED DOGS ~ AFFECTED will not show signs of the disease until approximately 7 years of age, having a vet check the eyes in the younger years will not tell you whether your dog is clear, carrier or affected. All of us with dogs over the age of about 10 that have received the all clear from an ophthalmologist can be assured that those dogs are either (green) clear or (yellow) carrier.

1. When two green dogs are mated, both parents being clear of the disease, all the puppies will be genetically clear.

2. When one parent is (green) clear and the other is a (yellow) carrier, approximately half of all the puppies will be (green) clear and half will be (yellow) carrier, meaning 50% of the litter will be carriers.

3. When one parent is (green) clear and the other is (red) affected then all of the puppies will be (yellow) carriers.

4. When both parents are (yellow) carriers, then on average a quarter of their puppies will be (green) clear, a quarter will be genetically affected (red) and half will be (yellow) carriers. That’s 75% of the litter with mutant genes.

5. When one parent is (yellow) carrier and the other parent is (red) affected then half the puppies will be (yellow) carriers and half will be (red) affected.

6. When both parents are (red) affected then all the offspring will be (red) affected.

In order to prevent PRA becoming endemic in Gordon Setters it is our responsibility as custodians of the breed to act now and share information. I have gone back to all previous litters, contacting as many buyers as possible in a relaxed and friendly manner, (so as not to cause alarm) and always included this question. ‘Has there been any blindness?’ Here are the results, together with the names of the parent dogs.

1999 ~ When I mated Kewstoke Kiss me Kate (definitely a carrier ~ died at 13 stone deaf but good eyesight)(Sh Ch Kewstoke Bryony Belle X Northinch Briar at Keepersgate) with Shannas Family Fortune (Sh Ch Wickenberry Philosopher at Liric X Sh Ch Shannas Midnight Shadow), both parents must have been carrying the recessive gene. In a litter of eight puppies, Will (Kewstoke Apprentice) and one other female sibling have the disease now. As Will has sired puppies all of his offspring will be carriers.

In 1998, I mated Kewstoke Caernie (Sh Ch Kewstoke Bryony Belle X Northinch Briar at Keepersgate) with Carek Dark Command (Shannas Family Fortune X Carek Bluebelle), both parents must have been carrying the recessive gene. From a litter of 9, I have been able to contact 7 owners there is 1 case of diagnosed PRA where the dog has been totally blind for the past 18 months. One bitch from the litter went to a show home and has been used in a breeding programme, there is 75% possibility that she will have been a carrier.

The owners of Carek Dark Command and Shannas Family Fortune should be asked to advise the committee whether these two dogs went blind with similar symptoms, if so at what age. Blindness in them will confirm that not only are they carriers, but also affected (red dogs) meaning that 100% of their offspring will also be carriers.

Judi Hartley (Arborsette) bred a litter using her Clementine and Monty.

1997 Blackstock Lightning (Blackstock Mist X Lourdace Gandolf at Amanorty) with Sh Ch Oaksett Northern Rising (Brimdale Mirage of Oaksett X Lourdace Muezli of Oaksett, it transpired that the dam was affected, she lost her sight at 9 years and the sire must have been a carrier as from 8 pups, 3 have developed PRA and are now blind. It is heartbreaking enough to have one of your darlings loose their sight, imagine how she feels now that two of the sons that she and David kept are both affected also.

It is highly unlikely that we two are the only persons in the UK to have bred Gordon Setters which developed PRA, is it?

I adore the Gordon Setter and never wish to be involved in any other breed. I have no wish to be ostracized by fellow members for making the subject of PRA an issue, but unlike the vision it won’t disappear.

Perhaps like me there are many members who were simply unaware. I hope that there are enough of you prepared to do the right thing, be honest and give support now to our breed and make the changes happen.

Wendy Smith 7th February 2009

Please note ~~ Since the initial circulation of this article, I have received confirmation from the owners that neither Shannas Family Fortune or Carek Dark Command went blind in their old age, which confirms that they were both carriers (yellow).

I have also received information on other dogs which went blind before 10 years of age and although not diagnosed with PRA were showing the same late onset symptoms. I am in the process of compiling a list of the affected dogs and carriers. This is only the tip of the iceberg, for every dog that develops PRA there will be many carriers in the breed.

The Gordon Setter organisations to which most of us have membership are now proactive and are in the process of collating some helpful information and guidance.

Wendy Smith 24th February 2009

Health Issue in Gordon Setters . February 2009

The UK Breed Clubs have been notified of dogs affected with late onset PRA in Gordon setters. Wendy Smith (Kewstoke) has written an informative paper on the Subject which has been endorsed by DR Jeff Sampson, DR Peter Bedford, and DR Malcolm Willis.

Kathryne Wrigley is the GSA Health representative, and is working with DR John Hadley and Sharon Green as the Breed Council Health Sub Committee. Kathryne is also the Breed Council Health Co-ordinator and in this role has liaised with the BGSC to invite their participation. Therefore Kathryne will act as Health Co-ordinator for the Breed

The Breed Council health team have liaised with the Animal Health Trust UK and Optigen USA to discuss the proposal to identify the mutant Gene which causes PRA. Once the marker is identified, these organisations can identify a DNA test whereby all Gordon Setters can be DNA tested to identify whether they are carriers, affected or clear dogs. This work has been previously been undertaken in other Breeds and again the Health Sub Committee are fully informed of the process and will share this information in detail at the seminar.

To identify the marker, AHT and Optigen require 12 samples from affected dogs and 6-8 samples from siblings of affected dogs. If you have an affected dog, or know of one we would encourage you to contact Optigen or AHT with the required information:

Contacts are: AHT : Genetics DNA Testing Department: dnatesting@aht.org.uk. www.aht.org.uk

Optigen: DNA testing: suepk@optigen.com, www.optigen.com

At this stage there is no advantage to taking samples from non affected dogs as there is no identified marker. Once the need for a test is proven and a marker identified we will work to ensure the Breed can undertake tests as a matter of expediency. However routine eye tests are encouraged.

The Gordon Setter Breed Council will do everything within its power to deal with this in an active and positive way and to that end we would welcome any well documented comments from anywhere in the world regarding PRA in British bred dogs.

Nicky Ackerley-Kemp
President GSA
yennadon@hrsupportconsultancy.co.uk

Elaine Roberts
Chairperson Breed Council
ergordons@aol.com

Updated : 26 July, 2010