Adult Onset Neuropathy (AN)

 UPDATES

Oct 2014     |     Nov 4, 2014     |     Jan 8, 2015     |     Jan 15, 2015     |     May 2015

 October 2014

HURRAH!!

IT’S WITH GREAT ENTHUSIASM WE ARE ANNOUNCING THE DISCOVERY OF THE MUTATION FOR “NEUROPATHY” IN ENGLISH COCKERS!

OUR RESEARCH TEAM CONSISTING OF DRS. GARY JOHNSON, JOAN COATES, AND CHARLES VITE LOCATED THE MUTATION IN AN OBSCURE GENE. IT HAS BEEN DETERMINED THAT THIS MUTATION IS RECESSIVELY INHERITED.

The Adult Onset Neuropathy test is available NOW on the OFA website under DNA tests at  http://www.offa.org/dnatesting/an.html

OFA will send a kit with instructions and supplies to collect DNA using a cheek swab and a barcoded card, which is treated to stabilize the DNA so it can be sent to our research lab with no special handling required.

Canine Genetic Diseases will run the test, and OFA will report results to the owners. This is now available on the OFA site (www.OFFA.org – click ORDER DNA TESTS and follow the links). Liz Hansen stated they are preparing information to go on their website, www.CanineGeneticDiseases.net. Owners of dogs showing clinical signs are eligible for a free DNA test for these affected (or suspected affected) dogs if samples are sent directly to our lab – the website will have a pdf file with instructions and a form to send a blood sample, or a cheek swab kit can be requested by emailing   This email address is being protected from spambots. You need JavaScript enabled to view it. . It is anticipated this info will be up on our website early next week. In addition, any owner that has DNA from their dogs banked here for any reason, or via blood sample in the CHIC DNA Bank, may request this test at the reduced fee of $35. This offer is only for dogs that are already DNA banked – it’s our way to say “thank you” to owners that made samples available for DNA research. Owners with dogs already DNA banked can also email This email address is being protected from spambots. You need JavaScript enabled to view it. This email address is being protected from spambots. You need JavaScript enabled to view it.  to request a test request for banked samples form.

Be sure to check the information above often during the next week. Keep in mind we’ve let the cat out of the bag before they had time to get the ducks in a row!

We are sincerely thankful to these doctors for their interest, commitment, and speed in identifying this mutation.

We can now eliminate the occurrence of this disease in the solid population. Special THANKS are also extended to ALL THOSE THAT PARTICIPATED IN THIS STUDY THROUGH THE SUBMISSION OF TISSUE AND/OR DNA. I would also like to THANK LIZ NEFF for her dedication and commitment to this project!

Addi Pittman
Liz Neff

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 November 4, 2014

At this point over 35 dogs have been tested and results were reported to owners. More results are pending.

Parti-colored English Cockers with ANY solid colored cockers in their pedigrees SHOULD be tested.

We now have solids that ‘tested’ carrier that are part of the genetic fabric of some parti-colored lines. All Hybrid cockers should be tested. Eradicate this disease before it is infused into our gene pool any further. We sincerely appreciate those breeders that have released test results into the public domain. This positive action will promote informed breeding decisions for our future generations. If you don’t know the status on your dog don’t breed it until you do! This applies to ALL health clearances. Be a responsible breeder/owner. Copies of all health clearances should be exchanged between stud dog owners and bitch owners before they are bred.

The AKC Online Breeder Classifieds program is in the process of adding each Parent Club’s health screening recommendations for consumers shopping for that breed. Consumers will be able to make an informed decision regarding health before they purchase a puppy/adult.

We have furnished the following information.

The ECSCA strongly recommends the following health screening tests prior to breeding. Documentation should be available and copies made for new owners.

  • OFA/Penn Hip evaluation for hip dysplasia (All ECS)
  • Progressive Retinal Atrophy DNA test performed by OptiGen (All ECS)
  • Patellar Luxation evaluation (All ECS)
  • BAER testing for parti-colored English Cockers (Parti-colored ECS)
  • Familiar Nephropathy DNA test performed by OptiGen (All ECS)
  • Adult Onset Neuropathy DNA test for solid colored English Cockers* (Solid colored/hybrid ECS)
  • ACVO Eye Exam (All ECS)

The ECSCA Breed Requirements for CHIC

Mandatory

Hip Dysplasia - OFA Evaluation/registration (All ECS)
Progressive Retinal Atrophy—OptiGen prcd DNA test (All ECS)
Patellar Luxation- OFA Evaluation/registration (All ECS)
Elective—Two of the following:
OFA Thyroid Evaluation (All ECS)
OptiGen Familial Nephropathy DNA test (All ECS)
BAER Test (Parti-colored ECS)
ACVO Eye Exam registered with OFA or CERF (All ECS)
Adult Onset Neuropathy DNA test* (All ECS)

*When testing be sure to choose ‘ADULT ONSET NEUROPATHY’ for English Cockers. Our breed does not have ‘DEGENERATIVE MYELOPATHY’ that occurs in many other breeds. If you own an English Cocker that was tested for DM you still need to test for AN!!

The ECSCA Health Committee
Addi Pittman, Chair

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 January 8, 2015

Over the past 20 years research efforts at the University of Missouri Animal Genetics Laboratory have focused on the identification of mutations responsible for heritable diseases of dogs. To date we have identified 25 disease-causing mutations. In addition, we have provided a genetic testing service for many of the mutations that we identified and for a few mutations discovered elsewhere. Each year our Animal Genetics Laboratory preforms approximately 9,000 DNA screening tests for inherited diseases in dogs.

Half of our successes have been made since the year 2010 when we began using whole genome sequencing as a preferred method for identifying disease-causing mutations. This technique involves the determination of the sequence of nearly all of the three billion nucleotides that comprise an individual dog’s DNA. We are testing and optimizing computing strategies that allow us to sort through these sequences from a diseased dog and pinpoint the one nucleotide change responsible for the disease. Thus far our use of whole genome sequencing has resulted in the identification of the causes for 13 canine diseases. Our current success rate for finding disease-causing mutations by whole genome sequence is about 35%; however, we haven’t given up on finding the 65% of so far unsolved diseases. We expect to identify several more disease-causing mutations as we improve our computer analysis and re-examine the whole genome sequences. Eleven of these discoveries were made with DNA from a single affected dog. We needed to sequence the genomes of two affected dogs before we could identify the other two disease-causing mutations.

One of the diseases that was solved only after we sequenced the genomes of two affected dogs was labeled adult-onset neuropathy of English Cocker Spaniels (ANECS). ANECS is progressive movement disorder due to a sensory and motor neuropathy which has been recognized as an autosomal recessive, hereditary disorder in English Cocker Spaniels. Clinical signs typically begin between 7 and 9 years of age and consist first of an uncoordinated gait or wobbling in the hind limbs. The stance in the hind limbs is wide-base and the hocks will drop lower to the ground. The disease eventually progresses to also involve the front limbs. Over time, the dogs are unable to walk and they may develop swallowing difficulties. The neurologic signs seem to progress gradually over 3 to 4 years and more slowly than those of degenerative myelopathy. So far the disease has only been clinically diagnosed in English Cocker Spaniels, although DNA tests indicate that the mutation also occurs in Field Spaniels where it is very rare. We have used DNA testing to search for the mutation in the other spaniel breeds, including the “American” Cocker Spaniel. So far we have only found it in English Cocker Spaniels and Field Spaniels.

As of the end of 2014, we have completed ANECS DNA tests on 227 English Cocker Spaniels. Samples from 135 English Cocker Spaniels were sent directly to us. The other 92 came to us via the Orthopedic Foundation for Animals. Fifty-one of the samples tested “AFFECTED/AT RISK,” indicating they inherited a mutant gene from each of their parents. These dogs either already have clinical signs of ANECS or are expected to develop the initial signs of the disease before their 10th birthday. A test result of ”CARRIER” was obtained for 59 of the English Cocker Spaniel samples. These dogs inherited a mutant gene from one parent and a normal gene from the other parent. So far as we have been able to tell, these dogs are perfectly normal. Nonetheless, the can produce AFFECTED/AT RISK offspring if bred to CARRIER or an AFFECTED/AT RISK mate. “NORMAL” test results were obtained for 56% of the tested English Cocker Spaniels. We believe that AFFECTED/AT RISK and CARRIER dogs are over-represented in our collection of DNA samples and that the percent of NORMALs in the entire English Cocker Spaniel population is much higher than 56%. In the past, only solid color English Cocker Spaniels were thought to develop ANECS; however, we have now detected the mutation in at least four roans and parti-color English Cocker Spaniels. We do not yet have coat color information on many of the tested dog so we are unable to estimate the prevalence of the mutation in the various coat colors.

We are eager to use whole genome sequencing to identify the mutations responsible for other heritable canine diseases. In addition, we are starting to sequence the genomes of healthy breed representatives that have made (or are likely to make) substantial contributions to their breeds. The sequence information from these dogs will be submitted to the NIOH maintained Sequence Read Archives, where they will be available to researchers around the world. Those breeds with normal control sequences already available in the Sequence Read Archives are more likely to be represented in future molecular genetic studies. The current cost for generating a whole genome sequence is about $5,000. Any Dog Club or individual wishing to fund the generation and analysis of a whole genome sequence to study a particular heritable disease or to provide a normal reference sequence for a particular breed should contact Gary Johnson at   This email address is being protected from spambots. You need JavaScript enabled to view it. .

View the OFA site list of tested dogs by going to  http://www.offa.org/, Advanced Search, select English Cocker Spaniel, then Adult Onset Neuropathy.

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 January 15, 2015

We recently mentioned a parti-colored English Cocker tested ‘Carrier’ for Adult Onset Neuropathy. This finding was a surprise because we have not received any reports of affected dogs that involve this sector of our breed. That didn’t mean it couldn’t happen. Additional dogs in this family were also tested. The mother and maternal aunt also tested ‘carrier.’ Three other dogs in the family pedigree tested ‘normal.’ A few more dogs in this family are now being tested. As a result of these findings all parti-colored dogs should be tested. This is our only option. We hope that everyone will choose to release their results into the public domain at the time the test is ordered through the OFA site. Since AN is a late-onset disease that occurs after prime reproductive years all breeding stock should be DNA tested prior to breeding before dissemination of the mutation occurs

This DNA test is very affordable ($65). When you fill out the paperwork, please include the color of the dog, sire and dam. Information on the disease and test are located on the OFA website at:  http://www.offa.org/dnatesting/an.html This link will guide through the process. PLEASE consider releasing all results for the good of our breed. OFA also maintains a list with dogs that have been tested ‘normal’ and those that are ‘affected and carriers.’ If you tested a dog previously, but did not choose to ‘release’ results at the time the kit was ordered you can submit a form to OFA reversing that decision. The OFA updates the list of tested dogs weekly. Pedigree information is usually available on tested dogs IF tested dogs have a sire/dam that have been tested previously for other diseases by OFA. You can view tested dogs at: www.offa.org Look on the left side of the home page for ‘advanced search’ click on that. You then choose BREED and look for English Cocker Spaniel, then choose REPORT TYPE, scroll to DNA and then choose Adult Onset Neuropathy. This list is not complete. It only involves dogs tested through OFA, Normal results (published automatically), and those that agreed to release all results. Many people have chosen not to release results, sadly. Missouri currently shows over 300 dogs have been tested. There is NO SHAME in sharing all results. If you love the breed and want to provide all English Cockers the opportunity to live a long, healthy, disease free life it starts with full-disclosure. Think about the welfare of the breed first…Do No Harm

Should you have questions about Adult Onset Neuropathy or other issues don’t hesitate to contact someone on the Health Committee.

Sincerely,
Addi Pittman, Chairman
Elizabeth Neff
Dr. Bruce Barrett
Joyce Winkels
Genelle Joseph

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 May 2015

Update courtesy of Liz Neff.

An informal meeting was held to discuss Adult Onset Neuropathy at the ECSCA 2015 national specialty, below you will find the items that were covered, questions answered during the meeting, and answers to questions that came up that took a little searching.

Thanks to all who attended as well as those who have asked for more information.

The following counts are different because some dogs were tested prior to the kits becoming available through OFA. These dogs were tested directly through the university as were dogs tested by other means such as DNA stored at Optigen, DNA from frozen semen, etc.

You can still test deceased dogs if there is enough DNA remaining at Optigen or one of the foreign DNA test companies. You can also test from frozen semen, but this is more expensive and requires a minimum of two straws,  however three or four straws are preferable. Semen contains very little DNA, so a larger volume is required to extract enough DNA. Although I have used this method with success, unfortunately it was more than twice as expensive. If there is a limited amount of frozen semen, you might consider  breeding a clear bitch to the frozen and testing the puppies.

Dogs tested through OFA as of the end of April, 2015.

339 tested
220 normal
92 carrier
27 affected

Dogs tested through U of Missouri

Total tested so far (thru 5/1) = 392
Of these, 239 tested NORMAL, 105 tested CARRIER, 48 tested AFFECTED/AT RISK

Tested directly thru lab (research or later testing) = 85 (36 Normal, 22 CARRIER, 27 AFFECTED/AT RISK)

The count is now over 400 dogs tested, which is awesome!

Dogs tested include almost all colors. Carriers have been found in solid and parti ECS. This is no longer a solid disease. Because of this it is very important to test ALL breeding stock. We can no longer make the assumption, as we have in the past, that a dog might be clear because of its pedigree. This disease clearly has no color or border boundaries. Carriers and Affected dogs have been found around the world. Just like PRCD and FN make sure to ask to see certification that a dog you are considering using has all three DNA tests.

In looking at these counts above it is important to remember that they include the initial study dogs. There were approximately 20 ECS in the initial study group and also blood/DNA was tested from several other Affected dogs who were not available for necropsy. These are dogs who were all diagnosed as clinically Affected first.

Breeders with concerns also test first so the Carrier and Affected percentages may be higher now than it ultimately will be after a larger portion of the breed has been tested.

These counts also include the initial control group of approximately 25 presumed Clear dogs used for comparison. All of those dogs tested Clear except one who tested Carrier.

Of the initial affected study dogs all were clinically Affected first and all but one were confirmed as Affected via necropsy. That one dog had spinal injury from another cause so was not initially used in the DNA research. That dog did test Affected when it's DNA was tested so it had AN plus the other spinal injury.

To date the researchers say that ALL dogs who have tested Affected AND have reached the age of onset have been clinically diagnosed as Affected.

All the early DNA Affected dogs have been tested twice and their owners have received a call from the researchers. They want to follow all dogs DNA testing Affected throughout their lives.

There have been a couple dogs with similar symptoms who tested Carrier only. It was later determined that these dogs had another cause for their disability. One had Lyme and has recovered after treatment. This shows the importance of having a Veterinary Neurologist examine any dog suspected of being Affected.  Dr Coates or Dr Vite can refer you or your vet to a Neurologist who knows how to diagnose AN. Please let us know if you need help with this. Assumptions do no one any good so if you suspect you have a case DNA test for the disease but also have the dog examined by your vet and referred to a Neurologist for full exam. If it is confirmed please let us know and we will help you any way we can.

The researchers want to make it clear that by using this test we can eliminate this disease without losing the great qualities of Carrier or even Affected dogs. We can breed Clear dogs to Affected or Carrier dogs. In a short time we can prevent producing Affected dogs and reduce the number of Carriers to eventually eliminate this disease just as we are working towards doing with PRCD and FN. It is possible to go from Affected to Clear in just two generations.

It is clear that for many years dogs with AN have been misdiagnosed as having other diseases. This shows the importance of breeder education about this disease and especially shows the importance of educating Vets about this disease. The researchers plan to publish their findings, hopefully later in 2015 or early. 2016. That will accomplish two things, it will begin to make all vets aware of the disease and it will allow peer review of the research.

Until then we can all start educating our vets by sharing with them the articles written about AN and the videos of Affected dogs. If they have questions they can email Dr Coates at U of Mo or Dr Vite at Penn. Both are great sources of information and can direct vets to the nearest Neurologist if further examination is needed. If you want write to me I will send you a packet of information to share with your vet. This email address is being protected from spambots. You need JavaScript enabled to view it.

The ECSCA will continue to fund testing for dogs owned or bred by members as long as the researchers continue to require more cases to study.  The owners must agree to follow the researchers directions, including PM when the time comes, and they must also agree to post their dog's results on the OFA list.

By posting results you are doing a great service to the future of our breed.

Sadly, there is still no treatment but, in time and with our help, maybe that will come. I did ask if the drugs being tried with ALS human patients might help, and those drugs really do very little or nothing at all. Maybe eventually stem cell research will give us hope but until then keeping the Affected dog fit and loved is the best we can do.

Again, THANKS to all those who allowed their wonderful dogs to participate in the research, both Affected dogs and Clear dogs for comparison. When asked for presumed Clear old dogs for the control group so many breeders jumped in to help that we had the 25 blood samples needed in less than two weeks!

THANKS to all those who have posted all of their results, good and bad!!! You are the ones who are truly dedicated to the future health of our breed. Even if it doesn't initially seem like it will help, the more breeders know the better off our dogs will be.

Another huge THANKS to the ECSCA, the ECSCA Health Committee, and The ECSCA Health and Rescue Organization as well as all of you who have contributed to our HRO!!!

 

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