Myotubular Myopathy 1

(X-linked centronuclear myopathy)

 

Gene: MTM1

Transmission: X-linked recessive

For an X-linked recessive genetic disease, a male must have one copy of the mutation in question to be at risk of developing the disease.  All affected males transmit the mutation to all the females of their offspring. A female must have two copies of the mutation in question to be at risk of developing the disease. Females with only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Labrador Retriever mutation: Substitution, MTM1 gene; c.465 C>A, p.(N155K), exon 7

Rottweiler mutation: Substitution, MTM1 gene; c.1151 A>C, p.(Q384P), exon 11

Boykin Spaniel mutation: Substitution, MTM1 gene; c.1467 C>T, p.(R512 STOP)

Medical system: Muscular

Breeds: Boykin Spaniel, Labrador Retriever, Rottweiler

Age of onset of symptoms: By 7 weeks of age.

X-linked myotubular myopathy is a severe and progressive disease caused by a defect in the myotubularin 1 protein which is required for normal muscle contraction.  Puppies affected by this disease are males, and will often show muscle atrophy as early as 7 weeks of age.  They generally appear smaller than other puppies in the litter, and may have difficulty with coordination and mobility.  Within a few weeks they may have difficulty holding their heads up, be unable to stand and collapse after exertion.  Most affected dogs are euthanized before reaching the age of 6 months.  Spontaneous and unique mutations in the MTM1 gene have occurred in several breeds.  As diseased male puppies are obvious and identify their mother as a carrier of the mutation, the spread of the mutation can be stopped relatively easily by DNA testing of potential female carriers.  Thus it is unlikely that the disease will spread widely within the breed affected.

 

References:

OMIA link: [1508-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Olby NJ, Friedenberg S, Meurs K, et al. (2020) A mutation in MTM1 causes X-Linked myotubular myopathy in Boykin spaniels. Neuromuscul Disord 30:353-359. [pubmed/32417001]

Lawlor MW, Beggs AH, Buj-Bello A, et al. (2016) Skeletal muscle pathology in X-linked myotubular myopathy: Review with cross-species comparisons. J Neuropathol Exp Neurol 75:102-10.  [pubmed/26823526]

Shelton GD, Rider BE, Child G, et al. (2015) X-linked myotubular myopathy in Rottweiler dogs is caused by a missense mutation in Exon 11 of the MTM1 gene. Skelet Muscle 5:1. [pubmed/25664165]

Beggs AH, Böhm J, Snead E, et al. (2010) MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proc Natl Acad Sci U S A 107:14697-702.  [pubmed/20682747]

 

Contributed by: Chloé Hicher et Noémie Lacroix, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).