title: A novel mutation in CLCN1 associated with feline myotonia congenita.
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.
authors.affiliation: Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri - Columbia, Columbia, Missouri, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gandolfi
authors.affiliation: Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri - Columbia, Columbia, Missouri, United States of America.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Daniel
authors.affiliation: Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri - Columbia, Columbia, Missouri, United States of America.
authors.forename: Dennis P
authors.initials: DP
authors.lastname: O'Brien
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Ling T
authors.initials: LT
authors.lastname: Guo
authors.affiliation: Winnipeg Humane Society, Winnipeg, Manitoba, Canada.
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Youngs
authors.affiliation: Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri - Columbia, Columbia, Missouri, United States of America.
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Leach
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Boyd R
authors.initials: BR
authors.lastname: Jones
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.affiliation: Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri - Columbia, Columbia, Missouri, United States of America.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lyons
mesh_terms: D000818:Animals; D002371:Cat Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002415:Cats; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D004576:Electromyography; D005091:Exons; D006041:Goats; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D009224:Myotonia Congenita / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology / Q000662:veterinary; D022821:RNA Splice Sites
chemical_list: D018118:Chloride Channels; D022821:RNA Splice Sites