A novel mutation in CLCN1 associated with feline myotonia congenita

Barbara Gandolfi, Rob J. Daniel, Dennis P. O'brien, Ling T. Guo, Melanie D. Youngs, Stacey B. Leach, Boyd R. Jones, G. Diane Shelton, Leslie A Lyons

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere109926
JournalPLoS One
Volume9
Issue number10
DOIs
StatePublished - Oct 30 2014
Externally publishedYes

Fingerprint

Myotonia Congenita
Felidae
Muscle
Cats
chloride channels
Chloride Channels
cats
mutation
Mutation
skeletal muscle
Skeletal Muscle
Screening
Cystathionine
cystathionine
screening
muscles
RNA Splice Sites
electromyography
Channelopathies
eyelids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gandolfi, B., Daniel, R. J., O'brien, D. P., Guo, L. T., Youngs, M. D., Leach, S. B., ... Lyons, L. A. (2014). A novel mutation in CLCN1 associated with feline myotonia congenita. PLoS One, 9(10), [e109926]. https://doi.org/10.1371/journal.pone.0109926

A novel mutation in CLCN1 associated with feline myotonia congenita. / Gandolfi, Barbara; Daniel, Rob J.; O'brien, Dennis P.; Guo, Ling T.; Youngs, Melanie D.; Leach, Stacey B.; Jones, Boyd R.; Shelton, G. Diane; Lyons, Leslie A.

In: PLoS One, Vol. 9, No. 10, e109926, 30.10.2014.

Research output: Contribution to journalArticle

Gandolfi, B, Daniel, RJ, O'brien, DP, Guo, LT, Youngs, MD, Leach, SB, Jones, BR, Shelton, GD & Lyons, LA 2014, 'A novel mutation in CLCN1 associated with feline myotonia congenita', PLoS One, vol. 9, no. 10, e109926. https://doi.org/10.1371/journal.pone.0109926
Gandolfi B, Daniel RJ, O'brien DP, Guo LT, Youngs MD, Leach SB et al. A novel mutation in CLCN1 associated with feline myotonia congenita. PLoS One. 2014 Oct 30;9(10). e109926. https://doi.org/10.1371/journal.pone.0109926
Gandolfi, Barbara ; Daniel, Rob J. ; O'brien, Dennis P. ; Guo, Ling T. ; Youngs, Melanie D. ; Leach, Stacey B. ; Jones, Boyd R. ; Shelton, G. Diane ; Lyons, Leslie A. / A novel mutation in CLCN1 associated with feline myotonia congenita. In: PLoS One. 2014 ; Vol. 9, No. 10.
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