Autosomal Recessive Centronuclear Myopathy in Labrador Retrievers
Centronuclear myopathy (CNM) in Labrador Retrievers is an hereditary myopathy characterised by skeletal muscle problems such as muscle weakness and exercise intolerance. It is also known as hereditary myopathy of the Labrador Retriever (HMLR).
The mutation, or change to the structure of the gene, probably occurred spontaneously in a single dog but once in the population has been inherited from generation to generation like any other gene. The disorder shows an autosomal recessive mode of inheritance: two copies of the defective gene (one inherited from each parent) have to be present for a dog to be affected by the disease. Individuals with one copy of the defective gene and one copy of the normal gene - called carriers - show no symptoms but can pass the defective gene onto their offspring. When two apparently healthy carriers are crossed, 25% (on average) of the offspring will be affected by the disease, 25% will be clear and the remaining 50% will themselves be carriers
The mutation responsible for this disease has been identified by a research group at the Ecole Nationale Vétérinaire d'Alfort in France (see below for reference). Using the information from their research, we have developed a DNA test for the disease. This test not only diagnoses dogs affected with this disease, but can also detect those dogs who are carriers, who display no symptoms of the disease but are able to produce affected pups. Under most circumstances, there will be a much greater number of carriers than affected animals in a population. It is important to eliminate such carriers from a breeding population since they represent a hidden reservoir of the disease that can produce affected dogs at any time.
The test is available now and information on submitting samples is given below.
Breeders will be sent results identifying their dog as belonging to one of three categories:
CLEAR: the dog has 2 copies of the normal gene and will neither develop CNM, nor pass a copy of the CNM gene to any of its offspring.
CARRIER: the dog has one copy of the normal gene and one copy of the mutant gene that causes CNM. It will not develop CNM but will pass on the CNM gene to 50% (on average) of its offspring.
AFFECTED: the dog has two copies of the CNM mutation and is affected with CNM. It will develop CNM at some stage during its lifetime, assuming it lives to an appropriate age.
Carriers can still be bred to clear dogs. On average, 50% of such a litter will be clear and 50% carriers; there can be no affected puppies produced from such a mating. Pups which will be used for breeding can themselves be DNA tested to determine whether they are clear or carrier.
Samples for this test can be either cheek swabs (obtainable free of charge from the address below) or 3 mls of blood in an EDTA tube. Samples for testing should be sent together with a completed DNA Testing form and the fee of £65-00 (inc VAT) for each sample to Genetic Services, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU. Payment should be by cheque or credit card. Enquiries should be made to Symone Ingram telephone +44 (0) 8700 509144 or fax +44 (0) 8700 502461 or via e-mail to dnatesting@aht.org.uk.
Request forms can be downloaded by clicking here.
The research to identify the mutation is described in:
Pelé,M., Tiret,L., Kessler,J-L., Blot,S. and Panthier,J-J. (2005) SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs. Human Molecular Genetics 14 1417-1427
