Abstract
A 9-month old male Jack Russell Terrier started showing paraparesis of the hindlimbs after a walk. Hospitalized, the dog went into cardiac arrest, and later died. Necroscopic examination revealed a severe thickness of the diaphragm, esophagus, and base of the tongue, leading to the diagnosis of muscular dystrophy. The histology confirmed the marked size variation, regeneration, and fibrosis replacement of the skeletal muscle fibers. Immunohistochemistry demonstrated the absence of dystrophin confirming the diagnosis. Transmission electron microscopy showed disarrangement of skeletal muscle fibers. Finally, whole-genome sequencing identified a ~368kb deletion spanning 19 exons of the canine dystrophin (DMD) gene. This pathogenic loss-of-function variant most likely explains the observed disease phenotype. The X-chromosomal variant was absent in seven controls of the same breed. Most likely, this partial deletion of the DMD gene was either transmitted on the maternal path within the family of the affected dog or arose de novo. This study revealed a spontaneous partial deletion in DMD gene in a Jack Russell Terrier showing a Duchenne-type muscular dystrophy due to non-functional dystrophin.
Highlights
Duchenne and Becker muscular dystrophies are X-linked recessive disorders, these forms occur predominantly in males
A causative genetic variant in Duchenne muscular dystrophy (DMD) was found in 96%
The reported partial deletion of approximately a fifth of the canine DMD gene leads to a true null allele of the DMD gene, with the lack of protein expression being experimentally confirmed
Summary
Duchenne and Becker muscular dystrophies are X-linked recessive disorders, these forms occur predominantly in males. They are caused by genetic variants in the dystrophin gene (DMD), the largest gene in the human genome, and as such are called dystrophinopathies [1]. The DMD gene spanning 2.4 Mb on the X chromosome encodes 79 exons for a 427-kD protein, called dystrophin, a rod-shaped protein located on the inner face of the plasma membrane of all types of myofibers and anchors cytoskeletal F-actin to the extracellular matrix protein laminin [2,3]. The central rod domain comprises the majority of the mass of the dystrophin molecule, forming a flexible, rod-shaped structure [4]. A causative genetic variant in DMD was found in 96%
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