Phenotype: Neuromuscular disorder characterized by generalized muscle weakness and fatigue, usually induced by exercise. Affected puppies collapse after a few minutes of rigorous exercise, but recover after some rest. Signs usually appear between 6 to 12 weeks of age.
Mode of Inheritance:Autosomal recessive
Alleles: N = Normal/Unaffected, CMS = Congenital myasthenic syndrome
Breeds appropriate for testing: Labrador Retriever
Explanation of Results:
Dogs with N/N genotype will not have congenital myasthenic syndrome and will not transmit this congenital myasthenic syndrome variant to their offspring.
Dogs with N/CMS genotype will not have congenital myasthenic syndrome, but are carriers. They will transmit this congenital myasthenic syndrome variant to 50% of their offspring. When bred to other carriers, matings are expected to produce 25% congenital myasthenic syndrome affected puppies.
Dogs with CMS/CMS genotype will have congenital myasthenic syndrome.
At least 15 business days; may be delayed beyond 15 business days if sample requires additional testing, or a new sample is requested.
Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder characterized by severe generalized skeletal muscle weakness and fatigue, usually induced by exercise. Puppies with this syndrome generally collapse after a few minutes of rigorous exercise, but typically recover after some rest. Signs usually appear between 6 to 12 weeks of age.
CMS is caused by a single nucleotide mutation (c.1010T>C) in exon 14 of the Collagen-like Tail Subunit of AsymmetricAcetylcholinesterase (COLQ) gene. This allele is predicted to cause improper anchoring of ColQ protein to the basal lamina of muscle cells and impair the termination of signal transmission within the neuromuscular junction, where motor neurons and muscle fibers connect. Malfunction of signal transmission affects muscle contraction. The mode of inheritance is autosomal recessive, which means that males and females are equally affected and that two copies of the mutation are needed to cause CMS.
According to the referenced paper below, only 2 Labrador Retrievers were reported to be affected and homozygous for this mutation but 16 out of 58 (28%) of their relatives were carriers. However, carriers can transmit the recessive allele to their offspring and can thus produce affected offspring if their mate also contributes a recessive allele. No carriers were found among 288 unrelated Labrador Retrievers, which suggests that the mutation is not widespread within the breed. Coincidentally, 2 human CMS patients were reported to be homozygous for an identical mutation (c.1010T>C), thus supporting the causality of the dog mutation. Screening of a random set of Labradors Retrievers at the VGL resulted in a frequency of 1.1% for the CMS disease allele.
Testing for CMS assists clinicians with differential diagnosis of CMS and helps breeders identify carriers among breeding stock and select appropriate mates to reduce the risk of producing CMS-affected offspring.
No copies of the CMS mutation detected. Dog is normal.
1 copy of the CMS mutation detected. Dog is a carrier and unaffected. If bred to another carrier, 25% of offspring are predicted to be affected.
2 copies of the CMS mutation detected. Dog is affected and will develop congenital myasthenic syndrome.
Rinz, C. J., Levine, J., Minor, K. M., Humphries, H. D., Lara, R., Starr-Moss, A. N., Guo, L. T., Williams, D. C., Shelton, G. D., & Clark, L. A. (2014). A COLQ missense mutation in Labrador Retrievers having congenital myasthenic syndrome. PLoS One, 9(8):e106425. doi: 10.1371/journal.pone.0106425