In other species: dog

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 310400 (trait) , 300415 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: X-linked recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2022

Cross-species summary: Also known as X-linked myotubular myopathy (XLMTM)

History: Kopke et al. (2022) reported the first case of myotubular myopathy in cats, and a likely causal variant.

Molecular basis: Kopke et al. (2022) reported that "Whole genome sequencing [of the single affected male Maine Coon cat] identified an underlying missense variant in myotubularin 1 (MTM1), a known candidate gene for X-linked myotubular myopathy."

Clinical features: Kopke et al. (2022): "A 7-month-old male Maine coon was evaluated for progressively worsening gait abnormalities and generalized weakness. Neurolocalization was to the neuromuscular system. Genetic testing for spinal muscular atrophy (LIX1) was negative. Given the progressive nature and suspected poor long-term prognosis, the owners elected euthanasia. Histopathology of skeletal muscle obtained post-mortem disclosed numerous rounded atrophic or hypotrophic fibers with internal nuclei or central basophilic staining. Using oxidative reactions mediated by cytochrome C oxidase and succinic dehydrogenase, scattered myofibers were observed to have central dark staining structures and a “ring-like” appearance. Given the cat's age and clinical history, a congenital myopathy was considered most likely, with the central nuclei and “ring-like” changes consistent with either centronuclear or myotubular myopathy. "

Prevalence: Kopke et al. (2022): "Besides the 339 cats and the reference genome cats without the variant, the variant additionally was genotyped by direct Sanger sequencing and not identified in 11 unrelated Maine coon cats, 1 random bred cat, and 1 cat of a different breed."

Associated gene: