OMIA 001967-9615 : Muscular dystrophy, Ullrich type in Canis lupus familiaris
Collagen VI is made up of three different subunits encoded by the COL6A1, COL6A2, and COL6A3 genes. Variants abolishing the function of either these genes lead to a severe muscular dystrophy phenotype in humans, the so-called Ullrich congenital muscular dystrophy. Based on the knowledge from humans, the identified canine COL6A1 nonsense variant seemed a very likely candidate causative variant for the Landseer disease. Steffen et al. (2015) genotyped 404 Newfoundland dogs and 473 dogs from diverse other breeds and did not find the mutant allele in these breeds.Clinical features: Generalized progressive muscle weakness is noticed very early in life. Due to the severity of the disease affected dogs are euthanized at 5-15 months of age (Steffen et al. 2015). Pathology: "All affected dogs showed pathological variation in muscle fiber size and most of the fibers were round to anisomorphic instead of having a (physiological) polygonal shape. Many small fibres were scattered throughout the biopsies, along with some hypercontracted fibres. Sporadically invading phagocytes grouped around degenerating fibers. Staining for acidic phosphatase showed an increase of activity, indicating degeneration to necrosis in a large number of fibres. Some biopsies correlated to an advanced stage of disease with distinct proliferation of the endomysial connective tissue and an increase of adipose tissue. These findings demonstrate different stages of muscular destruction with compensatory hypertrophy and replacement of lost fibers by connective tissue and fat cells. The histhopathological findings were typical for a muscular dystrophy. However, relatively normal immunohistochemistry findings with an anti-dystrophin antibody clearly showed that the muscular dystrophy in the Landseer dogs is different from the Duchenne/Becker type." (Steffen et al. 2015) Breed: Landseer. Associated gene:
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|COL6A1||collagen, type VI, alpha 1||Canis lupus familiaris||31||NC_006613.3 (39301718..39319895)||COL6A1||Homologene, Ensembl, NCBI gene|
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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.
|Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Year Published||PubMed ID(s)||Acknowledgements|
|Landseer||Muscular dystrophy, Ullrich type||COL6A1||nonsense (stop-gain)||c.289C>T||p.Q97*||2015||26438297|
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.
|2015||Steffen, F., Bilzer, T., Brands, J., Golini, L., Jagannathan, V., Wiedmer, M., Drögemüller, M., Drögemüller, C., Leeb, T. :|
|A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy. G3 (Bethesda) 5:2611-7, 2015. Pubmed reference: 26438297. DOI: 10.1534/g3.115.021923.|
|2013||Marioni-Henry, K., Haworth, P., Scott, H., Witte, P., Guo, L.T., Shelton, G.D. :|
|Sarcolemmal specific collagen VI deficient myopathy in a Labrador Retriever. J Vet Intern Med 28:243-9, 2013. Pubmed reference: 24147807. DOI: 10.1111/jvim.12224.|
- Created by Tosso Leeb on 23 Oct 2015
- Changed by Tosso Leeb on 23 Oct 2015