Abstract: Background: Muscular dystrophies occur in several dog breeds, arising from mutations in laminin α2, dystrophin, sarcoglycans, dystroglycan and collagen-6 genes. To date, there are no confirmed mutations causing any form of muscular dystrophy in American Staffordshire terriers.
Objective: To describe the clinical features, diagnostic testing and genetic mutation resulting in congenital muscular dystrophy in American Staffordshire terriers.
Animals: Two young client-owned American Staffordshire terrier littermates with suspected congenital neuromuscular disease.
Methods: Neurological examination, creatine kinase activity, infectious disease titers, cerebrospinal fluid analysis, and electrodiagnostic testing were performed. Muscle biopsies were collected for histopathology and immunohistochemical staining for localization of dystrophy-associated proteins. Genomic DNA was extracted from muscle and whole genome sequencing was performed on one of the affected dogs, and variants were compared to a database of over 700 unrelated dogs.
Results: Clinical signs included progressive weakness, joint contracture, and distal limb joint hyperlaxity. Creatine kinase activity was elevated in both dogs. Histopathology confirmed a dystrophic phenotype and immunofluorescence staining of muscle cryosections revealed an absence of staining for collagen-6. Whole genome sequencing identified a novel frameshift mutation in the COL6A3 gene that was homozygous and unique to the affected dog: Sanger sequencing confirmed homozygosity for the mutation in the affected dog and littermate.
Conclusions and Clinical Importance: A novel COL6A3 mutation resulting in Ullrich-like congenital muscular dystrophy was confirmed in American Staffordshire terriers. The clinical phenotype of distal joint contractures and laxity should alert clinicians to this disorder. A genetic test for this variant is now available.
