Myotubular myopathy 1 in Labrador Retrievers

Myotubular myopathy is a rare inherited muscle disease that manifests with progressive muscle atrophy that begins to develop shortly after birth. The first symptoms are hypotonia and weakness accompanied by breathing difficulties. Affected individuals have difficulty  eating and do not thrive. The gait is slow, staggering, with short steps.

In Labrador retrievers, the disease is caused by a missense mutation c.465C>A in the MTM1 gene, which encodes myotubularin. The mutation leads to impaired muscle growth and muscle fibre differentiation.

The mutation is X-linked. This means that it is localized on the X chromosome. Since the genotype of males is composed of X and Y chromosomes, they can only be healthy (unaffected by the mutation) or affected. The female genotype contains two X chromosomes, so females can be either healthy, carriers or affected. Female carriers do not show clinical signs but are able to pass the mutated allele to their offspring. Breeding of carrier females is not recommended. A genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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Reference:

Beggs, A.H., Böhm, J., Snead, E., Kozlowski, M., Maurer, M., Minor, K., Childers, M.K., Taylor, S.M., Hitte, C., Mickelson, J.R., Guo, L.T., Mizisin, A.P., Buj-Bello, A., Tiret, L., Laporte, J., Shelton, G.D. : MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proc Natl Acad Sci U S A 107:14697-702, 2010. Pubmed reference: 20682747