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

G. Diane Shelton, Katie M. Minor, Natassia M. Vieira, Louis M. Kunkel, Steven G. Friedenberg, Jonah N. Cullen, Ling T. Guo, Mayana Zatz, James R. Mickelson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)836-841
Number of pages6
JournalNeuromuscular Disorders
Issue number10
StatePublished - Oct 2022

Bibliographical note

Funding Information:
SGF is supported in part by an NIH Special Emphasis Research Career Award ( 1 K01 OD027058 ) in Pathology and Comparative Medicine sponsored by the Division of Comparative Medicine, Office of Research Infrastructure Programs. MZ is supported by the Sao Paulo Research Foundation (FAPESP/Brazil) [ 2013/08028-1 , 2014/50931-3 and 2020/09702-1 ] and the National Council for Scientific and Technological Development (CNPq) [ 465355/2014-5 ], and LMK supported in part by the National Institutes of Health R01AR064300 The authors thank Drs. Gena Silver, Nancy Hatfield, Sonnya Denis, and Andrea Molenbeek for searching medical records for clinical information, and the owners of the affected dogs for providing information on final clinical outcomes.

Publisher Copyright:
© 2022


  • Dog
  • Muscular dystrophy
  • Myopathy
  • Whole genome sequencing

PubMed: MeSH publication types

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


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