Open AccessClinical Findings and Prevalence of the Mutation Associated with Primary Ciliary Dyskinesia in Old English Sheepdogs
Author(s) -
Merveille A.C.,
Battaille G.,
Billen F.,
Deleuze S.,
Fredholm M.,
Thomas A.,
Clercx C.,
Lequarré A.S.
Publication year - 2014
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.12336
Subject(s) - primary ciliary dyskinesia , medicine , taqman , mutation , motile cilium , population , pathology , cohort , genotype , retrospective cohort study , gastroenterology , polymerase chain reaction , genetics , cilium , gene , biology , bronchiectasis , environmental health , lung
Background Primary ciliary dyskinesia ( PCD ) is generally a recessively inherited disorder characterized by dysfunction of motile cilia. A mutation in a new causative gene ( CCDC 39 ) has been identified in the Old English Sheepdog ( OES ). Objectives 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 . Animals 578 OES , including 28 affected and 550 clinically healthy dogs. Methods 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. CCDC39 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 CCDC39 mutation in these dogs. Results 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 ( IDA s). Molecular analysis revealed a reduced expression of CCDC 39 RNA and an absence of CCDC 39 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%). Conclusion and Clinical Importance CCDC 39 mutation is dispersed in a worldwide population and is responsible for PCD in this breed. Genetic testing might enable control of this disease.