Primary ciliary dyskinesia (PCD) in Alaskan Malamutes

The primary ciliary dyskinesia is a hereditary disease that is characterized by a defect of motile cilia of epithelial cells of the respiratory and reproductive tracts of male and female dogs and the epithelium of the nervous system. This disease is also known in humans and in several domestic animal species inclusive dogs.

The motile cilia of the airways clear the mucous membranes and help to propel pathogens and inhaled dust particles trapped in the mucous layer out of the airways.  The PCD causes dysfunction of the motile cilia due to the defects in the normal microscopic structure of motile cilia that result in reduced motility. This dysfunction is caused by shortening or loss of dynein arms of the cilia. Abnormal ciliary function typically leads to recurrent and chronic infections of respiratory tract. The puppies can have mucoid to mucopurulent nasal discharge and chronic productive cough. The respiratory problems can be very extensive and result in permanent damage to respiratory tract.

The ciliary epithelium of the reproductive tract ensures egg transport from the ovary to the uterus and sperm transport and therefore this disease causes reduced fertility of the affected individuals.

In some cases, hydrocephalus is also observed in connection with this disease.

In Alaskan Malamutes, a mutation c.43delA in NME5-gene has been identified that is responsible for this disease. It has an autosomal recessive mode of inheritance; it means that the disease occurs only in individuals who inherited the mutated gene from both parents. Individuals who inherited only one mutated gene from one parent will remain without clinical symptoms but pass the disease on to its offspring. Therefore, it is important to prevent spreading of this disease in the population of the Alaskan Malamutes by genetic testing.   Immunochemically, the mutation is associated with the absence of NME5 protein in the nasal epithelium of an affected dog.

The c.43delA mutation has not been proven in any of 72 tested dog breeds.

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Reference:

Anderegg L, Im Hof Gut M, Hetzel U, Howerth EW, Leuthard F, Kyöstilä K, et al. (2019): NME5 frameshift variant in Alaskan Malamutes with primary ciliary dyskinesia. PLoS Genet 15(9): e1008378.