Primary Ciliary Dyskinesia (Old English sheepdog type)

 

Gene: CCDC39

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, CCDC39 gene; c.286 C>T, p.(R96 STOP), exon3, chr.34.

Medical system: Respiratoiry

Breed: Maltese Terrier, Old English Sheepdog

Age of onset of symptoms: A few days after 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.

An immobile cilia syndrome involving chronic airway inflammation has been reported in the Old English Sheepdog since the 1980s. Further studies revealed that a situs inversus phenotype (right-left body axis reversal) could also be associated with the syndrome.  Note that motile cilia are involved in early embryogenesis for making body axis decisions.  Molecular studies identified a mutation within the CCDC39 gene as being responsible for these phenotypes.

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: [1540-9615]

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]

Merveille AC, Battaille G, Billen F, et al. (2014) Clinical findings and prevalence of the mutation associated with primary ciliary dyskinesia in old English sheepdogs. J Vet Intern Med 28:771-8.  [pubmed/24773602]

Merveille AC, Davis EE, Becker-Heck A, Legendre M, et al. (2011) CCDC39 is required for assembly of inner dyhein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nature Genetics 43(1):72-79. [pubmed/21131972]

Randolph JF, Castleman WL. (1984) Immotile cilia syndrome in two Old-English sheep dog littermates. J Small Anim Pract 25:679-686.  [https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1748-5827.1984.tb03381.x]