Dystrophin-Deficient Muscular Dystrophy in a Family of Shiba Inu Dogs with a Complex Deletion Encompassing DMD Exon 5.

BACKGROUND: Two Shiba Inu littermates presented for investigation of marked and persistent elevation of creatine kinase activities. METHOD AND RESULTS: Histopathology of muscle biopsy samples revealed a dystrophic phenotype and immunostaining confirmed an absence of dystrophin protein in both cases. Whole genome sequencing of one affected dog revealed a complex deletion in the DMD gene encompassing exon 5. Screening of 27 related dogs confirmed an X-linked inheritance. The variant was identified in three related male dogs. One littermate died from cardiac arrest and the other littermate had no clinical myopathic signs at the time of the manuscript's preparation. An additional related male dog reportedly died suddenly during grooming. CONCLUSION: This study adds a new breed to the canine dystrophinopathy spectrum having a ~17 kb deletion that encompasses exon 5 of DMD. This same exon 5 deletion has been identified in human dystrophin-deficient muscular dystrophy patients.