Genetic Testing for Inherited Polyneuropathy in Leonbergers
additonal info
http://www.leowatch.org/HTMLfiles/Healthissues/polyneuropathy.htm
http://www.cvm.umn.edu/vbs/faculty/Mickelson/lab/ipn/ipn/index.htm
http://www.leonbergerunion.com/health/healthe.htm (English)
http://www.leonbergerunion.com/health/healthd.htm (Deutsch)
http://www.leonbergerunion.com/health/testilpn1fr.pdf (Francais)
http://www.leonbergerunion.com/health/lpn1nedelands.pdf (Nederlands)
From the University
of Minnesota and the University of Bern:
Genetic Testing for Inherited Polyneuropathy in Leonbergers
Leonbergers may suffer from a hereditary neurological disease, which has
frequently been termed "inherited polyneuropathy (IPN)" or "Leonberger
polyneuropathy (LPN)" by veterinarians and breeders. Affected dogs suffer
from slowly worsening exercise intolerance and may develop gait
abnormalities, such as an exaggerated hitched step, especially in the hind
limbs. There is often wasting of the hind limb muscles as well.
Additionally, these dogs may have noisy breathing, a change in their bark,
or even difficulty breathing due to involvement of the larynx and laryngeal
folds in the throat. Eventually the disease may progress to the point where
the dog can no longer support its own weight.
Genetic research carried out at the University of Minnesota, the University
of Bern, and the University of California San Diego, indicates that
polyneuropathy is likely a group of several genetically distinct, but
clinically similar diseases. We have mapped two major genetic risk loci and
identified the causative mutation in one of these loci that we now term
LPN1. Dogs being homozygous mutant (two copies of the mutation) for this
mutation will typically develop neuropathy before they reach 3 years of age.
At this time we do not know whether dogs heterozygous for this mutation (one
copy of the mutation) might also develop mild clinical signs late in life,
but they will most likely not develop severe disease. The identified
mutation is responsible for approximately one third of the cases of
polyneuropathy in Leonbergers. The other two thirds of cases are apparently
caused by different genetic mutations.
The University of Minnesota and the University of Bern will offer genetic
testing for the identified LPN1 mutation starting July 1st, 2010. At this
time we recommend that all breeding dogs should be tested. We also recommend
avoiding breeding homozygous mutant dogs as well as matings that could
produce homozygous mutant dogs. We do not recommend excluding heterozygous
mutant dogs from breeding as this would significantly constrict the gene
pool of the Leonberger population and might lead to an increase in the other
forms of disease. However, dogs heterozygous for the LPN1 mutation should
only be mated to tested dogs which are free of the mutation. This will
ensure that no homozygous mutant offspring affected with the severe form of
the disease will be born.
At this time the implementation of genetic testing cannot completely
eliminate polyneuropathy from the Leonberger population. This LPN1 test
diagnoses only one of possibly several genetic risk factors. Thus, it is
still possible that affected offspring with a different genetic form of
polyneuropathy will result even from a mating of two dogs that both have
been tested free for this mutation. However, the current LPN1 test can
reliably eliminate one severe early-onset form of disease and significantly
reduce the overall frequency of neurological disease in Leonbergers.
Part 2 of 2
Dog owners who submitted blood samples for the research projects in either
Minnesota or Bern before 15-June-2010 will receive the results of this LPN1
genetic test at no cost within the next weeks. We are continuing to search
for the other genetic risk factors and blood samples from additional dogs
affected by apparent neurological disease will enhance this research. Dog
owners who submit a blood sample from an affected dog, together with
neurological exam or biopsy results, may receive the LPN1 test for free. In
North America, muscle and peripheral nerve biopsy specimens should be
submitted to:
Comparative Neuromuscular Laboratory
University of California, San Diego
Basic Science Building Room 2095
9500 Gilman Drive
La Jolla, CA 92093-0705
Phone: (858) 534-1537
Website
http://vetneuromuscular.ucsd.edu
Questions email
musclelab@ucsd.edu
Instructions for ordering the LPN1 test:
North America. Genetic testing will be performed at the University of
Minnesota Veterinary Diagnostic Laboratory. The preferred sample is 2-3 ml
of fresh blood collected in EDTA tubes.
Further information on sample submission, as well as the required submission
forms is available at:
http://www.cvm.umn.edu/vdl/ourservices/canineneuromuscular/home.html
The samples, packaged in a padded, leak-proof container, accompanied by a
submission form for each dog, should be sent by regular mail, without
cooling, to the Veterinary Diagnostic Laboratory:
Veterinary Diagnostic Laboratory
College of Veterinary Medicine
University of Minnesota
1333 Gortner Avenue
St Paul, MN 55108-1098
Phone: (612) 625-8787 or (800) 624-8787
Website: www.vdl.umn.edu
LPN-specific questions email:
lpninfo@umn.edu
The price per test is $85 and the expected turnaround time is 3 - 4 weeks.
Europe. For genetic testing a 2-5 ml EDTA blood sample of the animal in
question is required. The use of plastic tubes is recommended. Blood samples
should be sent in a padded envelope by regular mail without cooling to our
laboratory. They have to arrive within 3-4 days of sample taking. Order
forms can be downloaded from:
http://www.vetsuisse.unibe.ch/genetic/content/service/dog/index_eng.html
Please send the samples together with a signed order form to:
Institut für Genetik
Stichwort "Leonberger"
Bremgartenstrasse 109A
CH-3001 Bern
The direct genetic test costs 110.-- CHF or 75.-- EUR plus VAT. Initially,
we will run the test once a month. As we cannot run the complete procedure
for single individual samples it may take 1-2 months until the result is
communicated to the owners.
Questions and Answers from and for Leonberger Owners about the new LPN1
Genetic Test - Part 1
1. Should I have my Leonberger tested? Yes, we would like to encourage all
Leonbergers to be tested for LPN1 so we can obtain a complete as possible
picture of LPN1 in the Leonberger population. However, we do recommend the
following prioritization for testing:
a. Leonbergers to be bred in the next few months
b. Leonbergers that are in the current breeding pool, and those Leonbergers
that might be bred in the near future
c. Leonbergers showing clinical signs of LPN
d. Leonbergers that are offspring of a Leonberger that testing has shown to
have the LPN1 mutation, or direct offspring of Leonbergers showing clinical
signs before death (please note that if a DNA sample is currently present at
either University the sample will be tested even if the dog is deceased)
e. Leonbergers under the age of 3 that have no clinical signs of LPN and do
not have parents with the LPN1 mutation (or no information on the parents'
status)
f. Leonbergers over the age of 3 that have no clinical signs of LPN and do
not have parents with the LPN1 mutation (or no information on the parents'
status).
Please also make sure to have the results of any genetic test you have
performed released for publication. This is the only way we are going to be
able to understand the LPN1 affected population and attempt to breed LPN1
out of future Leonbergers.
2. I am planning on breeding my dog/bitch in the next few weeks/months, can
I expedite testing? Although there is no program for expedited testing, if
your testing will be in the US, you could send an email to
lpnifo@umn.edu
making a case for a quick turnaround.
3. Will this test be part of breeding requirements in the future? The
Leonberger Health Foundation, the Swiss Leonberger Club and other interested
parties will be working with the International Leonberger Union and
individual breed clubs to come up with breeding requirements/guidelines in
the very near future. Until those requirements/guidelines are in place, we
recommend that all breeding Leonbergers be tested, and as stated in the
initial release from the University of MN and the University of Bern,
breeding of homozygous affected Leonbergers be suspended and heterozygous at
risk Leonbergers be bred to only those Leonbergers, through testing, are
shown to be free of the mutation. Of course, a Leonberger showing clinical
signs of a neurological disease should not be bred even though they are
heterozygotes or clear for LPN1
4. I received results that show my Leonberger is homozygous affected for the
LPN1 mutation, what should I be looking for and doing to prepare me and my
Leonberger for LPN? There is already a wonderful support network of people
that have dogs with LPN. We are currently putting together a reference post
so information can be readily shared. Please look for the reference post in
the coming weeks.
5. If my Leonberger is homozygous affected for the LPN1 mutation, should I
have my dog/bitch neutered/spayed? Spaying or neutering your Leonberger is
a decision that should be made between you, your veterinarian, and possibly
your breeder. However, if your Leonberger is homozygous, we recommend the
dog/bitch not be bred at this time.
Questions and Answers from and for Leonberger Owners about the new LPN1
Genetic Test - Part 2
6. I am thinking of getting a Leonberger puppy in the near future, should I
only get one from parents that are free of the LPN1 mutation? One should
not immediately dismiss getting a puppy from a breeding with one Leonberger
that is heterozygous at risk for LPN1. As stated in the release from the
University of MN and the University of Bern, excluding heterozygous at risk
Leonbergers from the breeding population may have a negative impact on
genetic diversity and could possibly lead to an increase in other diseases.
Therefore we expect that breeders will breed heterozygous at risk
Leonbergers in the future because of other traits the dog/bitch can bring to
the breed. For example the breeder might choose to breed a heterozygous
stud to a LPN1 mutation free bitch because the dog has a history of
longevity in his line. You should always discuss health concerns/testing
with a breeder and should seek to fully understand the choices the breeder
has made in a particular breeding before choosing a puppy.
7. Should I call my breeder to see if my Leonberger's sire or dam is
affected and if/when I should have my Leonberger tested? All Leonberger
owners and breeders are receiving this information at the same time.
Although in the future, a breeder should be able to give you test results
for the LPN1 mutation, it is going to take some time before a breeder will
have test results for all of their breeding Leonbergers. Please be patient.
8. I don't remember if my Leonberger's DNA is at one of the Universities,
how can I find out? If you think your Leonberger's sample is at the
University of Minnesota, you can send an inquiry via email to
lpninfo@umn.edu.
When we have inquiry information for the University of
Bern, we will provide it.
9. I have moved since I submitted my Leonberger's sample. How can I update
my contact information to make sure I get the test results? In the US, send
your new contact information to
lpninfo@umn.edu. Please
include as much
identifying information as possible for you and your Leonberger to make this
easy on the university staff. When we have update information for the
University of Bern, we will provide it.
10. For Breeders - I just did a breeding and/or I chose to use a
heterozygous at risk Leonberger in my breeding. Can I have the puppies
tested before sending them to their new homes? The earliest recommended age
for having a blood sample taken from a Leonberger puppy is 6-8 weeks and
test results will take 4 weeks. In most cases, results would not be
available before the time one would normally be sending a puppy home.
However, if rear dew claws are present and you choose to have them removed,
the dewclaws can be sent for testing, giving a possible window for testing a
new litter. Please note: the removal of dewclaws is banned in some
countries, please know your country's regulations before removing and
sending in rear dew claws for testing.
11. This is great news! How can I help with further LPN studies?
a. Both the Leonberger Health Foundation and the Swiss Leonberger Club have
recently approved additional funding for the University of Minnesota and the
University of Bern to continue the polyneuropathy studies. If you would
like to send a donation to help support these and other Leonberger health
efforts, please send to one of the following locations:
Leonberger Health Foundation
c/o Suzi Ritter, Treasurer
1660 Beach Avenue., #7
Atlantic Beach, FL 32233 USA
OR
The Health Foundation of the Swiss Leonberger Club
Valiant Bank, CH-3001 Bern
SWIFT-Code: VABE CH 22, IBAN No. CH 63 0630 0016 0009 4710 4
b. The universities are requesting Leonberger owners continue to send
postmortem nerve biopsies from both affected and unaffected dogs to the lab
at UCSD until all polyneuropathy studies are complete. Additional
information on sending these biopsies is available in the initial release
and at
http://www.leowatch.org/HTMLfiles/Healthissues/polyneuropathy.htm
c. If you have a DNA sample already at one of the universities, please
continue to update the information on your dog, particularly information on
presentation of any polyneuropathy symptoms and/or changes in your dog's
health status. In the US, please utilize the form at
http://www.cvm.umn.edu/vbs/faculty/Mickelson/lab/ipn/ipn/index.htm
to send
updates.