Charcot-Marie-Tooth disease in Lancashire Heeler

Charcot–Marie–Tooth neuropathy is a hereditary disease of the peripheral nerves, which manifests itself mainly in weakness and muscle atrophy in the limbs, impaired coordination, reduced reflexes, and sometimes also deformities of the front limbs or reduced nerve conduction velocity. In the Lancashire Heeler, this disease also causes severe defects in the enamel of permanent teeth.

The disease is caused by a nonsense mutation c.5002C>T in the ITPR3 gene. The mutation is inherited in an autosomal recessive manner. This means that the disease only develops in individuals who inherit the mutated gene from both parents. Carriers of the mutated gene are clinically healthy, but they pass the mutation on to their offspring. In the case of mating two heterozygous individuals, theoretically 25% of offspring will be completely healthy, 50% will be carriers, and 25% will inherit the mutated gene from both parents and will therefore be affected by the disease.

Genetic testing can clearly reveal an animal's genotype and is a useful tool for breeders to prevent the unintentional breeding of affected puppies.

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References:

Hytönen, M.K., Rönkkö, J., Hundi, S., Jokinen, T.S., Suonto, E., Teräväinen, E., Donner, J., La Rovere, R., Bultynck, G., Ylikallio, E., Tyynismaa, H., Lohi, H. : IP3 receptor depletion in a spontaneous canine model of Charcot-Marie-Tooth disease 1J with amelogenesis imperfecta. PLoS Genet 21:e1011328, 2025. Pubmed reference: 39804930. DOI: 10.1371/journal.pgen.1011328.