Myotonia Congenita in Domestic Random Bred Cats

Myotonia congenita is a skeletal muscle disorder characterized by inability of the muscle to relax following voluntary contraction. Humans’ worldwide population prevalence is 1:100,000 persons. Studies on murine, human and goat confirmed myotonia associated with functional defects in chloride channels and mutations were found in CLCN1, which encodes for the most abundant chloride channel in muscles. Five random bred cats with clinical signs of myotonia congenita from Winnipeg Canada were examined at the University of Missouri, Columbia. The cats showed generalized muscle hypertrophy and an intermittent stiffness of gait; signs that are characteristic of myotonia congenita in other species.  Direct sequencing CLCN1 in affected and healthy cats revealed a mutation disrupting a donor splice site downstream exon 16 in all the affected cats. In vitro translation of the mutated protein predicted a premature truncation responsible for the lack of both highly conserved CBS1 and CBS2 (cystathionine β-synthase) domains, critical for the ion transport activity. Mutation screening in the Winnipeg random bred population was conducted using high resolution melting technology. A genetic test for population screening is now available and carrier cats from the feral population can be identified and neutered. Further studies in Xenopus oocites will elucidate the role of the mutation in the membrane conductance alteration, supporting the domestic cat as a comparative model for humans.