Dystrophin-Deficient Muscular Dystrophy in a Jack Russell Terrier With a Large Deletion in the Canine DMD Gene

A 6-month-old male Jack Russell Terrier presented with failure to thrive, lethargy, muscle atrophy, hypersalivation, and exercise intolerance. Similar signs were reported for the only other male puppy in the litter that died prematurely, whereas all the female puppies developed normally. An electromyography (EMG) test revealed abnormal electrical activity, such as complex repetitive discharges and fibrillation potentials. Cryosections of skeletal muscles revealed degenerative and regenerative myopathy with calcific deposits, consistent with a form of muscular dystrophy. Immunohistochemical testing demonstrated a lack of dystrophin, alongside upregulation of utrophin, and a subsequent reduction in dystrophin-associated proteins, which is consistent with dystrophin-deficient muscular dystrophy. Whole genome sequencing revealed a complex structural variant including a deletion of approximately 25.5 kb encompassing exons 8 and 9 of the DMD gene, which was absent in more than 1750 unrelated control genomes. This loss-of-function variant most likely accounts for the clinical presentation. Subsequent PCR testing revealed the presence of the wild-type allele in both parents and a normal female littermate. Amplification of the mutant allele could not be achieved. The mutant allele was likely transmitted from the mother to the index case and the presumed affected male littermate. It remains unresolved whether the mutant allele was transmitted over several generations in the maternal line or arose by a de novo mutation event in the germline of the mother. In conclusion, we describe a partial deletion of the DMD gene in a Jack Russell Terrier with a Duchenne-like muscular dystrophy phenotype due to non-functional dystrophin.