Novel COL6A3 Frameshift Mutation Causes Ullrich-Like Congenital Muscular Dystrophy in American Staffordshire Terrier Dogs

Two 10-month-old American Staffordshire terrier littermates presented for progressive weakness, joint contracture, and distal limb joint hyperlaxity beginning around 6 months of age. Neurological examination, serum creatine kinase activity, infectious disease titers, CSF 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 (WGS) was performed on one affected dog. Variants were compared to a database of nearly 700 unaffected dogs. Histopathology confirmed a dystrophic phenotype and immunofluorescence staining of muscle cryosections revealed an absence of staining for collagen-6. WGS identified a homozygous novel frameshift mutation in the COL6A3 gene, unique to the affected dog. Sanger sequencing confirmed the mutation in the affected dog and littermate. This report describes the clinical features and novel genetic mutation of Ullrich-like congenital muscular dystrophy in American Staffordshire terriers.