Clinical Findings and Prevalence of the Mutation Associated with Primary Ciliary Dyskinesia in Old English Sheepdogs. (12th March 2014)

• Record Type: Journal Article
• Authors: Merveille, A.‐C.; Battaille, G.; Billen, F.; Deleuze, S.; Fredholm, M.; Thomas, A.; Clercx, C.; Lequarré, A.‐S.
• Is Part Of: Journal of veterinary internal medicine. Volume 28:Number 3(2014:May/Jun.)
• Page Start: 771
• Page End: 778
• Publication Date: 2014-03-12
• Subjects: Veterinary medicine -- Periodicals; 636.0896
• DOI: 10.1111/jvim.12336
• Languages: English
• ISSNs: 0891-6640

Abstract

<abstract abstract-type="main" id="jvim12336-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jvim12336-sec-0001" sec-type="section"> <title>Background</title> <p>Primary ciliary dyskinesia (PCD) is generally a recessively inherited disorder characterized by dysfunction of motile cilia. A mutation in a new causative gene (<italic>CCDC39</italic>) has been identified in the Old English Sheepdog (OES).</p> </sec> <sec id="jvim12336-sec-0002" sec-type="section"> <title>Objectives</title> <p>To describe the clinical findings and the molecular changes of affected dogs and estimate the worldwide prevalence of the mutation in a large cohort of OES.</p> </sec> <sec id="jvim12336-sec-0003" sec-type="section"> <title>Animals</title> <p>578 OES, including 28 affected and 550 clinically healthy dogs.</p> </sec> <sec id="jvim12336-sec-0004" sec-type="section"> <title>Methods</title> <p>This retrospective study reviewed the data of OES diagnosed with PCD and OES tested for the mutation. Clinical data including results of physical examination and further investigations were obtained on 11/28 dogs. <italic>CCDC39</italic> expression was assessed by qRT‐PCR and Western blot analysis in affected dogs and healthy dogs. DNA was extracted on 561/578 dogs and a genetic test by Taqman technology was developed to genotype the <italic>CCDC39</italic> mutation in these dogs.</p> </sec> <sec id="jvim12336-sec-0005" sec-type="section"> <title>Results</title> <p>Clinical findings were recurrent nasal discharge and cough, pyrexia, leucocytosis, and bronchopneumonia. Ultrastructural defects were characterized by central microtubular abnormalities and decreased number of inner dynein arms (IDAs). Molecular analysis revealed a reduced expression of <italic>CCDC39 </italic>RNA and an absence of CCDC39 protein in affected dogs compared to healthy dogs. The mutation was more frequent in nonrandomly selected European OES population with a higher proportion of carriers (19%) compared to non‐European dogs (7%).</p> </sec> <sec id="jvim12336-sec-0006" sec-type="section"> <title>Conclusion and Clinical Importance</title> <p> <italic>CCDC39</italic> mutation is dispersed in a worldwide population and is responsible for PCD in this breed. Genetic testing might enable control of this disease.</p> </sec> </abstract>