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A novel mutation in CLCN1 associated with feline myotonia congenita.

Gandolfi B, Daniel RJ, O'Brien DP, Guo LT, Youngs MD, Leach SB, Jones BR, Shelton GD, Lyons LA - PLoS ONE (2014)

Bottom Line: 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).Muscle histopathology showed hypertrophy of all fiber types.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri - Columbia, Columbia, Missouri, United States of America.

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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Supramaximal repetitive nerve stimulation in a cat with myotonia congenita.Stimulation of the right tibial nerve at 3 Hz shows a decrement of 48.3% between the 1st and 30th waveforms.
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pone-0109926-g003: Supramaximal repetitive nerve stimulation in a cat with myotonia congenita.Stimulation of the right tibial nerve at 3 Hz shows a decrement of 48.3% between the 1st and 30th waveforms.

Mentions: Left tibial nerve motor conduction velocity was tested in two cats and found to be within normal limits. Supramaximal repetitive nerve stimulation was performed at the left distal hock in three cats at a repetition rate of 3 Hz. Decrement was observed in two cats tested, with percentage decreases in area under the curve between the 1st and 10th waveforms of 31.4% and 66.9% and percentage decreases of 48% and 67% between the 1st and 30th waveforms (Figure 3).


A novel mutation in CLCN1 associated with feline myotonia congenita.

Gandolfi B, Daniel RJ, O'Brien DP, Guo LT, Youngs MD, Leach SB, Jones BR, Shelton GD, Lyons LA - PLoS ONE (2014)

Supramaximal repetitive nerve stimulation in a cat with myotonia congenita.Stimulation of the right tibial nerve at 3 Hz shows a decrement of 48.3% between the 1st and 30th waveforms.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214686&req=5

pone-0109926-g003: Supramaximal repetitive nerve stimulation in a cat with myotonia congenita.Stimulation of the right tibial nerve at 3 Hz shows a decrement of 48.3% between the 1st and 30th waveforms.
Mentions: Left tibial nerve motor conduction velocity was tested in two cats and found to be within normal limits. Supramaximal repetitive nerve stimulation was performed at the left distal hock in three cats at a repetition rate of 3 Hz. Decrement was observed in two cats tested, with percentage decreases in area under the curve between the 1st and 10th waveforms of 31.4% and 66.9% and percentage decreases of 48% and 67% between the 1st and 30th waveforms (Figure 3).

Bottom Line: 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).Muscle histopathology showed hypertrophy of all fiber types.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri - Columbia, Columbia, Missouri, United States of America.

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.

Show MeSH
Related in: MedlinePlus