OMIA:002305-9615 : Muscular dystrophy, limb-girdle, type R3 (LGMDR3) in Canis lupus familiaris (dog)
Categories: Muscle phene
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2021
Cross-species summary: Previously known as Muscular dystrophy, limb-girdle, type 2D (LGMD2D): "At the 229th ENMC international workshop, Straub et al. (2018) reviewed, reclassified, and/or renamed forms of LGMD. The proposed naming formula was 'LGMD, inheritance (R or D), order of discovery (number), affected protein.' Under this formula, LGMD2D was renamed LGMDR3." (OMIM 608099)
Species-specific name: LGMD2D; alpha-sarcoglycanopathy
Molecular basis: Mickleson et al. (2021): "Genetic mapping and whole genome sequencing" in a "cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria" "identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA)" as a likely causal variant.
Clinical features: Clinical signs first becomes apparent in affected Miniature Dachshunds when they are young, at approximately 6 months of age, and is slowly progressive (Mickelson et al, 2021). Dogs with this disease will show signs such as exercise intolerance, a stiff gait, difficulty swallowing and pneumonia (Mickelson et al., 2021). Blood tests will show consistent high levels of the muscle enzyme, creatinine kinase (CK) in the blood and urine tests will show myoglobinuria, an excess of myoglobin indicating muscle breakdown (Mickelson et al, 2021). A marked and persistent elevation in CK, even if the dog is not showing clinical signs, may be an indicator of disease in young Miniature Dachshunds (Mickelson et al, 2021).
IT thanks DVM student Dilshara Hill, who provided the basis of this contribution in May 2023.
Pathology: Mickelson et al. (2021): "Pathological changes in muscle biopsies from the four affected miniature dachshunds were dystrophic in nature regardless of the clinical presentation ... . Immunofluorescent antibody staining ... showed a normal pattern for the dystrophin rod domain and patchy staining with the antibody against the c-terminus of dystrophin. Staining for utrophin and laminin α-2 was similar to control muscle. Clusters of regenerating fibers were highlighted with the antibody against developmental myosin heavy chain (dMHC). Staining for α-sarcoglycan and γ-sarcoglycan was absent and staining was decreased for β-sarcoglycan."
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SGCA||sarcoglycan, alpha (50kDa dystrophin-associated glycoprotein)||Canis lupus familiaris||9||NC_051813.1 (26959303..26972755)||SGCA||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.
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|
|1280||Miniature dachshund||Muscular dystrophy, limb-girdle, type R3||SGCA||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||9||g.26166312G>A||c.G224A||p.(W75*)||2021||33407862|
Cite this entry
|2021||Mickelson, J.R., Minor, K.M., Guo, L.T., Friedenberg, S.G., Cullen, J.N., Ciavarella, A., Hambrook, L.E., Brenner, K.M., Helmond, S.E., Marks, S.L., Shelton, G.D. :|
|Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D. Skelet Muscle 11:2, 2021. Pubmed reference: 33407862 . DOI: 10.1186/s13395-020-00257-y.|
- Created by Frank Nicholas on 09 Jan 2021
- Changed by Frank Nicholas on 09 Jan 2021
- Changed by Imke Tammen2 on 04 May 2023