A Novel Mutation in CLCN1 Associated with Feline Myotonia Congenita |
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Authors: | 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 |
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Institution: | 1. Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri – Columbia, Columbia, Missouri, United States of America.; 2. Department of Pathology, University of California San Diego, La Jolla, California, United States of America.; 3. Winnipeg Humane Society, Winnipeg, Manitoba, Canada.; 4. Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.; University of Valencia, Spain, |
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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. |
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