Primary Ciliary Dyskinesia (STK36 type)

Gene: STK36

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: Substitution, STK36 gene; c.2868-1 G>A, p.(M957P fs STOP 11), chr.37.

Medical system: Respiratory

Breeds:

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.

A single mature Australian Shepherd with a history of recurring nose infections and nasal discharge was examined.  Nasal and tracheal biopsies revealed aberrant cilia ultra-structure on electron microscope examination.  Molecular studies on genomic DNA from the animal revealed a homozygous mutation in the STK36 gene, whose protein product is needed for normal cilia structural formation. The mutation was not found in 281 Australian Shepherd control animals.  The clinical significance of this mutation for the Australian Shepherd breed remains to be determined.

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)