Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype

Neuromuscul Disord. 2022 Oct;32(10):836-841. doi: 10.1016/j.nmd.2022.08.001. Epub 2022 Aug 6.


A form of dystrophinopathy with mild or subclinical neuromuscular signs has been previously reported in a family of Labrador retrievers. Markedly and persistently elevated creatine kinase activity was first noted at 6 months of age. Skeletal muscle biopsies revealed a dystrophic phenotype, with dystrophin non-detectable on western blotting and immunohistochemical staining, and with increased utrophin expression. In this report we demonstrate with western blotting that α-dystroglycan is present at essentially normal levels. Whole genome sequencing has also now revealed an approximately 400kb tandem genomic DNA duplication including exons 2-7 of the DMD gene that was inserted into intron 7 of the wild type gene. Skeletal muscle cDNA from 2 cases contained DMD transcripts as expected from an in-frame properly-spliced exon 2-7 tandem insertion. A similar 5' duplication involving DMD exons 2-7 has been reported in a human family with dilated cardiomyopathy but without skeletal myopathy. This is the 3rd confirmed mutation in the DMD gene in Labrador retrievers.

Keywords: Dog; Muscular dystrophy; Myopathy; Whole genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dogs
  • Dystrophin / genetics
  • Dystrophin / metabolism
  • Exons / genetics
  • Humans
  • Introns
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Duchenne* / pathology
  • Phenotype


  • Dystrophin