Myotubular myopathy 1 (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.

Mutation: Substitution, MTM1 gene; c.455C>T, p.(Ala152Val), exon6, chromosome X.

Breed: Maine Coon

Medical system: Muscular, neuromuscular.

Age of onset of symptoms: By 4 months of age.

Myotubular (or centronuclear) myopathies are a family of congenital myopathies that can be caused by mutations in several genes.  As seen in humans and in the dog, these myopathies can have autosomal transmission resulting from mutations in the DNM2, BIN1, RYR1 or PTPLA/HACD1 genes, or X-linked transmission resulting from mutations in the MTM1 gene.

A single adolescent male Maine coon cat was presented with progressive gait anomalies, general weakness and difficulties in feeding.  A diagnosis of congenital myopathy was made, which on histological analysis of muscle tissue was further classified as myotubular (centronuclear) myopathy.  DNA analysis identified a mutation in the MTM1 gene as the presumed cause of the phenotype.  Due to the X-chromosome location of the MTM1 gene and consistent with X chromosome recessive heredity, it was presumed that the mother of the affected cat was a silent carrier.  No other DNA analysis of the pedigree in question could be performed.  However, 11 unrelated Main Coon cats tested negative for the mutation as did 339 additional cats of unspecified breeds.  Thus, the frequency of the MTM1 mutation within the Maine Coon breed remains undetermined.

References:

OMIA link: [1508-9685]

Kopke MA, Diane Shelton G, Lyons LA, et al. (2022) X-linked myotubular myopathy associated with an MTM1 variant in a Maine coon cat. J Vet Intern Med 36:1800-1805. [pm/35962713]

Contributed by: Laurie Bellemare and Justine Moreau, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)