Centronuclear Myopathy (CNM) in Labrador Retrievers
Centronuclear myopathy is a hereditary myopathy of Labrador Retrievers characterized by generalized loss of muscle tone and control.
Phenotype: Signs of centronuclear myopathy include generalized loss of muscle tone and control, exercise intolerance, and an awkward gait. CNM typically manifests in puppies at 2-5 months of age.
Mode of Inheritance:Autosomal recessive
Alleles: N = Normal, CNM = Centronuclear myopathy
Breeds appropriate for testing: Labrador Retriever
Explanation of Results:
Dogs with N/N genotype will not have centronuclear myopathy and cannot transmit this CNM variant to their offspring.
Dogs with N/CNM genotype will not be affected by centronuclear myopathy, but are carriers. They will transmit this CNM variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% centronuclear myopathy-affected puppies.
Dogs with CNM/CNM genotype will have centronuclear myopathy.
Centronuclear myopathy (CNM) is a hereditary myopathy of Labrador Retrievers resulting from a mutation in the protein tyrosine phosphatase-like member A gene (PTPLA). PTPLA codes for a dehydratase enzyme that functions in the production of long chain fatty acids, these molecules are thought to be involved in muscle homeostasis. While the precise role of PTPLA in this disease is unknown, the CNM mutation has been shown to lead to a reduction in normal gene product.
The disease is inherited in an autosomal recessive fashion with both sexes equally affected.
This condition has also been called type II muscle fiber deficiency, autosomal recessive muscular dystrophy, and hereditary myopathy.
CNM typically manifests in puppies at age 2-5 months. Signs of CNM include generalized loss of muscle tone and control, exercise intolerance, and an awkward gait. Dogs with one normal copy and one mutant copy of the gene (heterozygous) do not display signs. Breeding two carriers is predicted to produce 25% affected offspring and 50% carriers of the disease.
Testing for CNM can assist clinicians, owners, and breeders in identifying affected and carrier dogs. Breeders can use results from the test as a tool for selection of mating pairs to avoid producing affected dogs.
Note: This test is specific for the CNM mutation described in Labrador Retrievers.
No copies of CNM mutation detected. Dog is normal.
1 copy of CNM mutation. Dog is a carrier and unaffected. If bred to another carrier, 25% of offpsring are predicted to be affected.
2 copies of CNM mutation. Dog is affected.
Pelé, M., Tiret, L., Kessler, J.L., Blot, S., & 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(11), 1417-1427. doi: 10.1093/hmg/ddi151
Maurer, M., Mary, J., Guillaud, L., Fender, M., Pelé, M., Bilzer, T., Olby, N., Penderis, J., Shelton, G.D., Panthier, J.J., Thibaud, J.L., Barthélémy, I., Aubin-Houzelstein, G., Blot, S., Hitte, C., & Tiret, L. (2012). Centronuclear myopathy in Labrador Retrievers: A recent founder mutation in the PTPLA gene has rapidly disseminated worldwide. PloS One 7(10): e46408. doi: 10.1371/journal.pone.0046408