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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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Related in: MedlinePlus

The hypertrophic tongue in a cat affected with myotonia congenita.The tongue is very enlarged and constantly protrudes from the mouth.
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pone-0109926-g001: The hypertrophic tongue in a cat affected with myotonia congenita.The tongue is very enlarged and constantly protrudes from the mouth.

Mentions: Abnormalities on general physical examination common to all five affected cats included a restricted jaw opening, halitosis, varying degrees of gingivitis, pseudoptyalism, marked dental calculus accumulation with palpable loose teeth and evidence of poor grooming habits. Severe muscle hypertrophy was found along the cervical spine, proximal aspects of all limbs (Video S1) and the tongue, which protruded from the mouth (Figure 1 and Video S2). One cat showed signs of respiratory distress (stridor, open mouth breathing) upon examination that lasted for several minutes. Serum creatine kinase (CK) activity was mildly elevated in only one of the five cats tested.


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)

The hypertrophic tongue in a cat affected with myotonia congenita.The tongue is very enlarged and constantly protrudes from the mouth.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0109926-g001: The hypertrophic tongue in a cat affected with myotonia congenita.The tongue is very enlarged and constantly protrudes from the mouth.
Mentions: Abnormalities on general physical examination common to all five affected cats included a restricted jaw opening, halitosis, varying degrees of gingivitis, pseudoptyalism, marked dental calculus accumulation with palpable loose teeth and evidence of poor grooming habits. Severe muscle hypertrophy was found along the cervical spine, proximal aspects of all limbs (Video S1) and the tongue, which protruded from the mouth (Figure 1 and Video S2). One cat showed signs of respiratory distress (stridor, open mouth breathing) upon examination that lasted for several minutes. Serum creatine kinase (CK) activity was mildly elevated in only one of the five cats tested.

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