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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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Myotonic discharges in a cat with myotonia congenita.EMG recorded from the biceps femoris muscle showed a sustained run of initially positive biphasic to triphasic spikes with a firing frequency of 240 Hz. Note also the waxing and waning in amplitude of the spike train.
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pone-0109926-g002: Myotonic discharges in a cat with myotonia congenita.EMG recorded from the biceps femoris muscle showed a sustained run of initially positive biphasic to triphasic spikes with a firing frequency of 240 Hz. Note also the waxing and waning in amplitude of the spike train.

Mentions: Appendicular as well as axial skeletal muscle was tested. Prolonged insertional activity with myotonic discharges were identified in all skeletal muscles tested and showed the characteristic waxing and waning amplitude (Figure 2 and Video S4). The discharges had a mean amplitude of 277 µV (130 µV, 240 µV and 470 µV) and a mean frequency of 300 Hz (240 Hz, 260 Hz and 400 Hz). Because of the remarkably high frequency of the myotonic discharges, the sound generated from these discharges on the EMG loudspeaker resembled a swarm of bees.


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)

Myotonic discharges in a cat with myotonia congenita.EMG recorded from the biceps femoris muscle showed a sustained run of initially positive biphasic to triphasic spikes with a firing frequency of 240 Hz. Note also the waxing and waning in amplitude of the spike train.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0109926-g002: Myotonic discharges in a cat with myotonia congenita.EMG recorded from the biceps femoris muscle showed a sustained run of initially positive biphasic to triphasic spikes with a firing frequency of 240 Hz. Note also the waxing and waning in amplitude of the spike train.
Mentions: Appendicular as well as axial skeletal muscle was tested. Prolonged insertional activity with myotonic discharges were identified in all skeletal muscles tested and showed the characteristic waxing and waning amplitude (Figure 2 and Video S4). The discharges had a mean amplitude of 277 µV (130 µV, 240 µV and 470 µV) and a mean frequency of 300 Hz (240 Hz, 260 Hz and 400 Hz). Because of the remarkably high frequency of the myotonic discharges, the sound generated from these discharges on the EMG loudspeaker resembled a swarm of bees.

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