Test Detail

Primary ciliary dyskinesia (PCD)

General · Dog

Hereditary disorder of the motile cilia that alters mucociliary clearance of the airways, the function of ependymal cilia and, in the male, sperm flagellar motility. It presents with cough and mucopurulent rhinorrhoea from the first weeks of life, recurrent pneumonia and bronchiectasis; in some cases situs inversus (Kartagener syndrome) or hydrocephalus appear. It is inherited in an autosomal recessive manner and the causal variants differ by breed: CCDC39 in the Old English Sheepdog (Bobtail) and NME5 in the Alaskan Malamute.
Inheritance patternAutosomal recessive (OMIA:001540-9615 and OMIA:002206-9615).
Gene / MutationOld English Sheepdog (Bobtail): CCDC39 (CFA34) c.286C>T, p.(Arg96*) (OMIA:001540-9615; PMID 21131972). Alaskan Malamute: NME5 (CFA11) c.43delA, p.(Thr15Leufs*56) (OMIA:002206-9615; PMID 31479451).
PenetranceHigh penetrance in homozygotes, with variable expressivity; heterozygotes are asymptomatic carriers. No carriers with clinical signs have been described.
Codeeqlp
Turnaround time15 days
Price52,60 €

Incidence

Old English Sheepdog (Bobtail): in a non-random sample of 578 dogs, the CCDC39 variant was more frequent in the European population (19% carriers) than in the non-European one (7%) (Merveille 2014). Alaskan Malamute: the variant was identified in a family with two of six affected puppies and was not detected in control genomes (Anderegg 2019). There are isolated clinical cases in other breeds without confirmed molecular basis.

Breeder management

- Test breeding animals with the breed-specific test (CCDC39 in Bobtail, NME5 in Alaskan Malamute)
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier may be mated with a clear animal; test the offspring intended for breeding
- Avoid the spread of the allele to lines where it is not present
- Consider screening imported breeding animals before incorporating them into breeding

Specialist notes

Differential diagnosis with chronic bronchitis, megaoesophagus, immunodeficiencies and respiratory foreign body. Functional diagnostic tests (nasal nitric oxide measurement, saccharin test, mucosal biopsy with electron microscopy) guide the diagnosis, but molecular confirmation is the breed-specific test. In the Alaskan Malamute, concurrent hydrocephalus suggests involvement of the ependymal cilia.

References

1. Merveille AC et al. (2011) CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nat Genet 43(1):72-78. PMID: 21131972
2. Merveille AC et al. (2014) Clinical findings and prevalence of the mutation associated with primary ciliary dyskinesia in Old English Sheepdogs. J Vet Intern Med 28(3):771-778. PMID: 24773602
3. Anderegg L et al. (2019) NME5 frameshift variant in Alaskan Malamutes with primary ciliary dyskinesia. PLoS Genet 15(8):e1008378. PMID: 31479451

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