In other species: domestic cat

Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 310400 (trait) , 300415 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0010683: X-linked centronuclear myopathy

Mendelian trait/disorder: yes

Mode of inheritance: X-linked recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2010

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

Inheritance: Beggs et al. (2010) presented pedigree information that was inconsistent with autosomal recessive inheritance but consistent with X-linked recessive inheritance.

Molecular basis: Based on the close histopathological resemblance to human MTM1 (see link to MIM entry above), Beggs et al. (2010) sequenced all 15 exons of the comparative candidate MTM1 gene in two affected male Labrador Retrievers, one obligate female carrier Labrador Retriever, and several non-affected dogs from other breeds. A potentially causative missense mutation (c.465C>A; p.N155K) in exon 7 was confirmed by further sequencing ("seven affected males, representing each of the affected families, were found to be hemizygous for this change, whereas three obligate female carriers were all heterozygous") and genotyping (the mutation "was not seen in any of 237 unrelated and unaffected Labrador Retrievers from throughout North America, Europe, and Australia, nor was it detected in any of 59 additional control dogs from 25 other breeds"). Shelton et al. (2015) sequenced the same gene in a group of Australian Rottweilers segregating in a similar (X-linked) manner for very similar clinical signs, and discovered a different causal missense mutation (c.1151A>C; p.Q384P) in exon 11. Subsequent genotyping of this mutation in UK Rottweilers and other (unrelated) Australian Rottweliers showed no trace of the mutation, suggesting that this mutation is fairly new. In an affected male Boykin spaniel, Olby et al. (2020) identified a likely causal variant, namely "a premature stop codon in exon 13 of MTM1 (ChrX: 118,903,496 C > T, c.1467C>T, p.Arg512X). . . . The puppy's dam was heterozygous for the variant, and 3 male puppies from a subsequent litter all of which died by 2 weeks of age were hemizygous for the variant."

Breeds: Boykin Spaniel (Dog) (VBO_0200214), Labrador Retriever (Dog) (VBO_0200800), Rottweiler (Dog) (VBO_0201143).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: