OMIA 001508-9615 : Myotubular myopathy 1 in Canis lupus familiaris
In other species: domestic cat
Category: Muscle phene
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: X-linked recessive
Considered a defect: 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, Labrador Retriever, Rottweiler.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MTM1||myotubularin 1||Canis lupus familiaris||X||NC_051843.1 (121040671..121137182)||MTM1||Homologene, Ensembl, NCBI gene|
By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.
WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1459||Boykin Spaniel||Myotubular myopathy 1||MTM1||nonsense (stop-gain)||Naturally occurring variant||X||g.118903496C>T||c.1467C>T||p.(R512*)||2020||32417001|
|63||Labrador Retriever||Myotubular myopathy 1||MTM1||missense||Naturally occurring variant||CanFam3.1||X||g.118885117C>A||c.465C>A||p.(N155K)||XM_005641935.3; XP_005641992.1||rs1152388426||2010||20682747||Genomic coordinates in CanFam3.1 and EVA ID provided by Robert Kuhn|
|91||Rottweiler||Myotubular myopathy 1||MTM1||missense||Naturally occurring variant||CanFam3.1||X||g.118901282A>C||c.1151A>C||p.(Q384P)||XM_005641935.3; XP_005641992.1||2015||25664165||Genomic position in CanFam3.1 provided by Robert Kuhn and Mateo Etcheveste.|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2020||Olby, N.J., Friedenberg, S., Meurs, K., DeProspero, D., Guevar, J., Lau, J., Yost, O., Guo, L.T., Shelton, G.D. :|
|A mutation in MTM1 causes X-Linked myotubular myopathy in Boykin spaniels. Neuromuscul Disord 30:353-359, 2020. Pubmed reference: 32417001. DOI: 10.1016/j.nmd.2020.02.021.|
|Ross, J.A., Tasfaout, H., Levy, Y., Morgan, J., Cowling, B.S., Laporte, J., Zanoteli, E., Romero, N.B., Lowe, D.A., Jungbluth, H., Lawlor, M.W., Mack, D.L., Ochala, J. :|
|rAAV-related therapy fully rescues myonuclear and myofilament function in X-linked myotubular myopathy. Acta Neuropathol Commun 8:167, 2020. Pubmed reference: 33076971. DOI: 10.1186/s40478-020-01048-8.|
|2017||Mack, D.L., Poulard, K., Goddard, M.A., Latournerie, V., Snyder, J.M., Grange, R.W., Elverman, M.R., Denard, J., Veron, P., Buscara, L., Le Bec, C., Hogrel, J.Y., Brezovec, A.G., Meng, H., Yang, L., Liu, F., O'Callaghan, M., Gopal, N., Kelly, V.E., Smith, B.K., Strande, J.L., Mavilio, F., Beggs, A.H., Mingozzi, F., Lawlor, M.W., Buj-Bello, A., Childers, M.K. :|
|Systemic AAV8-mediated gene therapy drives whole-body correction of myotubular myopathy in dogs. Mol Ther 25:839-54, 2017. Pubmed reference: 28237839. DOI: 10.1016/j.ymthe.2017.02.004.|
|2016||Lawlor, M.W., Beggs, A.H., Buj-Bello, A., Childers, M.K., Dowling, J.J., James, E.S., Meng, H., Moore, S.A., Prasad, S., Schoser, B., Sewry, C.A. :|
|Skeletal Muscle Pathology in X-Linked Myotubular Myopathy: Review With Cross-Species Comparisons. J Neuropathol Exp Neurol 75:102-10, 2016. Pubmed reference: 26823526. DOI: 10.1093/jnen/nlv020.|
|2015||Goddard, M.A., Mack, D.L., Czerniecki, S.M., Kelly, V.E., Snyder, J.M., Grange, R.W., Lawlor, M.W., Smith, B.K., Beggs, A.H., Childers, M.K. :|
|Muscle pathology, limb strength, walking gait, respiratory function and neurological impairment establish disease progression in the p.N155K canine model of X-linked myotubular myopathy. Ann Transl Med 3:262, 2015. Pubmed reference: 26605308. DOI: 10.3978/j.issn.2305-5839.2015.10.31.|
|Shelton, G.D., Rider, B.E., Child, G., Tzannes, S., Guo, L.T., Moghadaszadeh, B., Troiano, E.C., Haase, B., Wade, C.M., Beggs, A.H. :|
|X-linked myotubular myopathy in Rottweiler dogs is caused by a missense mutation in Exon 11 of the MTM1 gene. Skelet Muscle 5:1, 2015. Pubmed reference: 25664165. DOI: 10.1186/s13395-014-0025-3.|
|Snyder, J.M., Meisner, A., Mack, D., Goddard, M., Coulter, I.T., Grange, R., Childers, M.K. :|
|Validity of a Neurological Scoring System for Canine X-Linked Myotubular Myopathy. Hum Gene Ther Clin Dev 26:131-7, 2015. Pubmed reference: 26086764. DOI: 10.1089/humc.2015.049.|
|2012||Grange, R.W., Doering, J., Mitchell, E., Holder, M.N., Guan, X., Goddard, M., Tegeler, C., Beggs, A.H., Childers, M.K. :|
|Muscle function in A canine model of X-linked myotubular myopathy. Muscle Nerve 46:588-91, 2012. Pubmed reference: 22987702. DOI: 10.1002/mus.23463.|
|2010||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. DOI: 10.1073/pnas.1003677107.|
|2008||Cosford, KL., Taylor, SM., Thompson, L., Shelton, GD. :|
|A possible new inherited myopathy in a young Labrador retriever. Can Vet J 49:393-7, 2008. Pubmed reference: 18481550.|
- Created by Frank Nicholas on 26 Oct 2010
- Changed by Frank Nicholas on 28 Sep 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 24 Feb 2015
- Changed by Frank Nicholas on 15 Oct 2016
- Changed by Imke Tammen2 on 18 Sep 2021
- Changed by Imke Tammen2 on 15 Nov 2021
- Changed by Frank Nicholas on 25 May 2022