A novel mutation in CLCN1 associated with feline myotonia congenita

PLoS One. 2014 Oct 30;9(10):e109926. doi: 10.1371/journal.pone.0109926. eCollection 2014.


Myotonia congenita (MC) is a skeletal muscle channelopathy characterized by inability of the muscle to relax following voluntary contraction. Worldwide population prevalence in humans is 1:100,000. Studies in mice, dogs, humans and goats confirmed myotonia associated with functional defects in chloride channels and mutations in a skeletal muscle chloride channel (CLCN1). CLCN1 encodes for the most abundant chloride channel in the skeletal muscle cell membrane. Five random bred cats from Winnipeg, Canada with MC were examined. All cats had a protruding tongue, limited range of jaw motion and drooling with prominent neck and proximal limb musculature. All cats had blepharospasm upon palpebral reflex testing and a short-strided gait. Electromyograms demonstrated myotonic discharges at a mean frequency of 300 Hz resembling the sound of a 'swarm of bees'. Muscle histopathology showed hypertrophy of all fiber types. Direct sequencing of CLCN1 revealed a mutation disrupting a donor splice site downstream of exon 16 in only the affected cats. In vitro translation of the mutated protein predicted a premature truncation and partial lack of the highly conserved CBS1 (cystathionine β-synthase) domain critical for ion transport activity and one dimerization domain pivotal in channel formation. Genetic screening of the Winnipeg random bred population of the cats' origin identified carriers of the mutation. A genetic test for population screening is now available and carrier cats from the feral population can be identified.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cat Diseases* / genetics
  • Cat Diseases* / metabolism
  • Cat Diseases* / pathology
  • Cat Diseases* / physiopathology
  • Cats
  • Cell Membrane* / genetics
  • Cell Membrane* / metabolism
  • Chloride Channels* / genetics
  • Chloride Channels* / metabolism
  • Dogs
  • Electromyography
  • Exons
  • Goats
  • Humans
  • Mice
  • Muscle, Skeletal* / metabolism
  • Muscle, Skeletal* / pathology
  • Muscle, Skeletal* / physiopathology
  • Mutation*
  • Myotonia Congenita* / genetics
  • Myotonia Congenita* / metabolism
  • Myotonia Congenita* / mortality
  • Myotonia Congenita* / physiopathology
  • Myotonia Congenita* / veterinary
  • RNA Splice Sites


  • Chloride Channels
  • RNA Splice Sites