Primary ciliary dyskinesia (PCD) in Old English Sheepdogs (Bobtails)
Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by insufficient function of cilia of epithelial mucous membrane. Typical symptoms of PCD are recurrent infection of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome –internal organs misplaced to wrong side of body, which can be caused by improper motility of cilia in the early embryonic stage). The function of mucus clearance from the airways is ineffective and results in chronic inflammation of nasal cavities, windpipe (trachea) and lower airways. Symptoms such as sneezing, nasal discharge, cough, breathlessness and lethargy occur at the age of several weeks or months.
PCD symptoms have been recorded in 19 breeds; the search for causal mutation in individual breeds still continues.
Research of PCD in Old English Sheepdog breed resulted in discovery of responsible mutation in CCDC39-gene. It is a substitution p.Arg96X (C>T transition in the third exon of CCDC39-gene), causing generation of premature stop codon during protein synthesis affecting the correct motility of epithelial cilia.
The disease is inherited as a recessive trait. Dogs that have two copies of the mutant gene are affected with PCD, though the typical signs may be present to a various degree. Dogs carrying one copy of the mutant gene have no external symptoms affecting their health.
If two heterozygous dogs are mated, 25% of the offspring in the litter are expected to be healthy, 50 % of the offspring are expected to be carriers and 25 % of the offspring inherit the mutant allele from both parents and are expected to have PCD. The molecular-genetic test enables to identify the presence or absence of the mutation and determine a potential carrier of the disease.
Merveille at al.; CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs; Nature Genetics; 2010