Primary Ciliary Dyskinesia (Alaskan Malamute type)

Gene: NME5

Transmission: Autosomal recessive

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease, but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion, NME5 gene; c.43 del. A, p.(T15L fs STOP 56)

Medical system: Respiratory, (neurologic, reproduction)

Breeds: Alaskan Malamute, Siberian Husky

Age of onset of symptoms: From birth.

Primary ciliary dyskinesia (PCD) in dogs is a ciliopathy, a genetic disease of cilia.  Cilia are microscopic hair-like structures found on the apical surfaces of certain epithelial cells, notably within the respiratory and reproductive tracts.   Coordinated wave-like movement of cilia help to clear mucus, dust, and bacteria from airway surfaces, or to propel gametes within the reproductive system.  The major clinical signs of PCD involve the respiratory system and include coughing, sneezing, excessive nasal discharge as well as infections including sinusitis, bronchitis, and pneumonia.  These symptoms will respond to medical treatment but are recurrent.

In the Alaskan Malamute, puppies from an inbred litter presented with persistent cough and nasal discharge and PCD was suspected.  An additional Alaskan Malamute from an unrelated litter presented with similar respiratory signs and also with hydrocephaly.  Note that the ependymal cells within the central nervous system are ciliated and are involved in cerebral spinal fluid circulation.  Electron microscopy of respiratory epithelium revealed structural anomalies in cilia.  Molecular studies identified a homozygous mutation in the NME5 gene as being responsible for the PCD phenotypes observed.  A survey of 407 Alaskan Malamutes revealed a carrier frequency for the mutation of 1.7%.

Several breed specific gene mutations have been associated with PCD in dogs:

Alaskan malamutes – NME5 gene, OMIA link: [2206-9615]

Old English Sheepdog – CCDC39 gene, OMIA link: [1540-9615]

Australian Sheepdog – STK36 gene, OMIA link: [2623-9615]

References:

OMIA link: [2206-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Anderegg L, Im Hof Gut M, Hetzel U, et al. (2019) ME5 frameshift variant in Alaskan Malamutes with primary ciliary dyskinesia. PLoS Genet 15:e1008378.  [pubmed/31479451]

Contributed by:  Katherine Bourgon and Catherine Lalanne, Class of 2028, Faculty of Veterinary Medicine, University of Montreal.  (Translation, DWS)