Canine lafora disease: An unstable repeat expansion disorder

Thilo von Klopmann, Saija Ahonen, Irene Espadas-Santiuste, Kaspar Matiasek, Daniel Sanchez-Masian, Stefan Rupp, Helene Vandenberghe, Jeremy Rose, Travis Wang, Peixiang Wang, Berge Arakel Minassian, Clare Rusbridge

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Canine Lafora disease is a recessively inherited, rapidly progressing neurodegenerative disease caused by the accumulation of abnormally constructed insoluble glycogen Lafora bodies in the brain and other tissues due to the loss of NHL repeat containing E3 ubiquitin protein ligase 1 (NHLRC1). Dogs have a dodecamer repeat sequence within the NHLRC1 gene, which is prone to unstable (dynamic) expansion and loss of function. Progressive signs of Lafora disease include hypnic jerks, reflex and spontaneous myoclonus, seizures, vision loss, ataxia and decreased cognitive function. We studied five dogs (one Chihuahua, two French Bulldogs, one Griffon Bruxellois, one mixed breed) with clinical signs associated with canine Lafora disease. Identification of polyglucosan bodies (Lafora bodies) in myocytes supported diagnosis in the French Bulldogs; muscle areas close to the myotendinous junction and the myofascial union segment had the highest yield of inclusions. Postmortem examination of one of the French Bulldogs revealed brain Lafora bodies. Genetic testing for the known canine NHLRC1 mutation confirmed the presence of a homozygous mutation associated with canine Lafora disease. Our results show that Lafora disease extends beyond previous known breeds to the French Bulldog, Griffon Bruxellois and even mixed-breed dogs, emphasizing the likely species-wide nature of this genetic problem. It also establishes these breeds as animal models for the devastating human disease. Genetic testing should be used when designing breeding strategies to determine the frequency of the NHLRC1 mutation in affected breeds. Lafora diseases should be suspected in any older dog presenting with myoclonus, hypnic jerks or photoconvulsions.

Original languageEnglish (US)
Article number689
Issue number7
StatePublished - Jul 2021


  • Canine
  • Chihuahua
  • Dodecamer repeat mutation
  • EPM2A
  • French Bulldog
  • Griffon Bruxellois
  • Hypnic jerk
  • Muscle biopsy
  • NHLRC1
  • Photoconvulsions
  • Progressive myoclonic epilepsy

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Space and Planetary Science
  • Palaeontology


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