Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 608099 (trait) , 600119 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0011968: autosomal recessive limb-girdle muscular dystrophy type 2D

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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."

Breed: Dachshund, Miniature (Dog) (VBO_0200408).
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: