title: A novel mutation of the CLCN1 gene associated with myotonia hereditaria in an Australian cattle dog.
abstract: BACKGROUND
  Heritable myotonia is a genetic muscle disorder characterized by slow relaxation of skeletal muscles. The main clinical signs are skeletal muscle stiffness, especially after vigorous contraction, and muscle hypertrophy. Muscle stiffness may be enhanced by inactivity, and often is relieved by exercise. Myotonia can be inherited in an autosomal dominant or recessive manner (Thomsen- or Becker-type myotonia, respectively). In mice, goats, Miniature Schnauzer dogs, and most affected humans, the disorder is caused by mutations in CLCN1, which encodes the skeletal muscle voltage-gated chloride channel, Cl1C-1.
  
  
  OBJECTIVE
  We hypothesized that an Australian Cattle Dog with generalized muscle stiffness and hypertrophy examined at the Ontario Veterinary College would have a mutation in the CLCN1 gene.
  
  
  METHODS
  A pure-bred Australian Cattle Dog from Ontario, Canada, was used.
  
  
  METHODS
  Based on clinical signs and electromyographic test results, a diagnosis of myotonia hereditaria was made, and a muscle biopsy was collected for genetic analysis.
  
  
  RESULTS
  Sequence data obtained from the affected dog confirmed that it was homozygous for a single base insertion in the CLCN1 coding sequence. This mutation would result in a truncated ClC-1 protein being expressed, which, based on molecular evidence from other studies, would result in functionally compromised chloride conduction in the skeletal muscles of the animal.
  
  
  CONCLUSIONS
  To the authors' knowledge, this report describes the Ist case of myotonia in an Australian Cattle Dog and represents the 1st non-Schnauzer canine myotonia to be genetically characterized. In addition, we developed a polymerase chain reaction-based genetic screen to detect heterozygotes with this mutation in the at-large Australian Cattle Dog population.
authors.affiliation: Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Finnigan
authors.forename: W J Brad
authors.initials: WJ
authors.lastname: Hanna
authors.forename: Roberto
authors.initials: R
authors.lastname: Poma
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bendall
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D008969:Molecular Sequence Data; D009132:Muscles / Q000503:physiopathology*; D009154:Mutation; D009222:Myotonia / Q000235:genetics / Q000662:veterinary*; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D018118:Chloride Channels