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.
Highlights
A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified
We report here the discovery of the first mutation in the canine sarcoglycan alpha subunit (SGCA) gene in young adult miniature dachshunds that leads to a form of limb-girdle muscular dystrophies (LGMD) with clinical signs that include subclinical myopathy with hyperCKemia, exercise intolerance, progressive weakness, variable dysphagia and pneumonia, and myoglobinuria
The veterinarians reported that all four dogs had persistently elevated creatine kinase (CK) activities and a myopathic clinical phenotype varying from generalized weakness and exercise intolerance with myoglobinuria to pharyngeal dysphagia (Fig. 1)
Summary
A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified. The most common forms include the X-linked Duchenne and Becker muscular dystrophies associated with mutations in the dystrophin gene (DMD), and the limb-girdle muscular dystrophies (LGMD) associated with autosomal dominant (LGMD1) or autosomal recessive (LGMD2) mutations in several genes [1, 2]. Further sub-classification of LGMDs is based on an alphabetical system following the order of Mutations in the dystrophin gene (DMD) result in a wide range of clinical severity in human patients, including the milder Becker type MD (BMD) to the severe Duchenne type MD (DMD). Patients with LGMD may have a wide range of clinical phenotypes including both the severe DMD and milder BMD types with onset from childhood to young adult. It is difficult to reach a diagnosis of a specific sarcoglycanopathy based on immunoreactivity alone
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