Sarcoglycan A Mutation in Miniature Dachshund Dogs Causes Limb Girdle Muscular Dystrophy 2D

Abstract

BackgroundA cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria and markedly elevated serum creatine kinase activities were identified. MethodsMuscle biopsy histopathology, immunofluorescence microscopy, and western blotting, were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis.ResultsMuscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene ( SGCA ). Affected dachshunds were confirmed on several continents. ConclusionsThis first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.

Novel COL6A3 frameshift variant in American Staffordshire Terrier dogs with Ullrich‐like congenital muscular dystrophy

“…Autosomal recessive or dominant forms of limb-girdle muscular dystrophy associated with variants in the sarcoglycan (SCG) genes are reported in Boston terrier (OMIA:002122-9615) 12 and miniature dachshund dogs (OMIA:002305-9615). 13 Most recently, variants in the collagen-6 (COL6A) genes are reported in Labrador retrievers (OMIA:002274-9615), 4 Landseer Newfoundland dogs (OMIA:001967-9615), 2 and in this report, an American Staffordshire Terrier.…”