OMIA 001540-9615 : Ciliary dyskinesia, primary, CCDC39-related in Canis lupus familiaris
Category: Respiratory system phene
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2011
Species-specific name: Primary ciliary dyskinesia
Species-specific symbol: PCD
Species-specific description: Several types of primary ciliary dyskinesia exist. See also 'OMIA002206-9615 : Ciliary dyskinesia, primary, NME5-related in Canis lupus familiaris' and 'OMIA000573-9615 : Ciliary dyskinesia, primary, generic in Canis lupus familiaris'.
Previously, references to case reports of dogs with primary ciliary dyskinesia with unknown genetic cause were listed here, but these have been moved to the generic entry for this disease [3/6/2022].
Mapping: By conducting a GWAS on 5 affected and 15 control Old English Sheepdogs (that all traced back to a common ancestor), each genotyped with an Affymetrix v2.0 Canine SNP chip, Merveille et al. (2011), from the LUPA consortium, identified a 15Mb region of autozygosity on chromosome CFA34.
Molecular basis: Sequencing of the six most-likely candidate genes in the CFA34 candidate region (see Mapping section) region identified a nonsense mutation in the CCDC39 gene, which encodes coiled-coil domain-containing protein 39. By searching for CCDC39 mutations in PCD cases in humans (where PCD is a heterogeneous inherited disorder), they were able to identify a new cause of human PCD. This study highlights the power of canine genomic studies to inform knowledge of human inherited disorders that are genetically heterogeneous.
Clinical features: As reported by Merveille et al. (2014), "Clinical findings were recurrent nasal discharge and cough, pyrexia, leucocytosis, and bronchopneumonia."
Prevalence: After genotyping "578 OES [Old English Sheepdogs], including 28 affected and 550 clinically healthy dogs" for the mutation discovered by Merveille et al. (2011) (see Molecular section), Merveille et al. (2014) reported that ""The mutation was more frequent in nonrandomly selected European OES population with a higher proportion of carriers (19%) compared to non-European dogs (7%).
Breed: Old English Sheepdog.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|CCDC39||coiled-coil domain containing 39||Canis lupus familiaris||34||NC_051838.1 (13860663..13816636)||CCDC39||Homologene, Ensembl, NCBI gene|
By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.
WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|266||Old English Sheepdog||Ciliary dyskinesia, primary||CCDC39||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||34||g.13952270G>A||c.286C>T||p.(R96*)||2011||21131972||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2014||Merveille, A.C., Battaille, G., Billen, F., Deleuze, S., Fredholm, M., Thomas, A., Clercx, C., Lequarré, A.S. :|
|Clinical findings and prevalence of the mutation associated with primary ciliary dyskinesia in old English sheepdogs. J Vet Intern Med 28:771-8, 2014. Pubmed reference: 24773602. DOI: 10.1111/jvim.12336.|
|2011||Merveille, A.C., Davis, E.E., Becker-Heck, A., Legendre, M., Amirav, I., Bataille, G., Belmont, J., Beydon, N., Billen, F., Clément, A., Clercx, C., Coste, A., Crosbie, R., de Blic, J., Deleuze, S., Duquesnoy, P., Escalier, D., Escudier, E., Fliegauf, M., Horvath, J., Hill, K., Jorissen, M., Just, J., Kispert, A., Lathrop, M., Loges, N.T., Marthin, J.K., Momozawa, Y., Montantin, G., Nielsen, K.G., Olbrich, H., Papon, J.F., Rayet, I., Roger, G., Schmidts, M., Tenreiro, H., Towbin, J.A., Zelenika, D., Zentgraf, H., Georges, M., Lequarré, A.S., Katsanis, N., Omran, H., Amselem, S. :|
|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 43:72-8, 2011. Pubmed reference: 21131972. DOI: 10.1038/ng.726.|
|2000||Clercx, C., Peeters, D., Beths, T., McEntee, K., Votion, D., Snaps, F., Henroteaux, M., Jorissen, M. :|
|Use of ciliogenesis in the diagnosis of primary ciliary dyskinesia in a dog Journal of the American Veterinary Medical Association 217:1681-1685, 2000. Pubmed reference: 11110460.|
|1984||Randolph, J.F., Castleman, W.L. :|
|Immotile cilia syndrome in two Old-English sheep dog littermates. J. Small Anim. Pract. 25:679-686, 1984.|
- Created by Frank Nicholas on 21 Jul 2011
- Changed by Frank Nicholas on 10 Aug 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 29 Jun 2013
- Changed by Frank Nicholas on 02 May 2014
- Changed by Imke Tammen2 on 06 Apr 2021
- Changed by Imke Tammen2 on 03 Jun 2022