OMIA 001522-9615 : Oculoskeletal dysplasia 1 in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 108300 , 154780

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2010

Cross-species summary: This disorder has been renamed in OMIA on the basis of the review by Miyadera et al. (2012)

Species-specific symbol: osd1; drd1

Species-specific description: Oculoskeletal dysplasia is a collagen disorder characterized by short-limbed dwarfism, particularly of the forelimbs, and vitreous dysplasia with associated retinal detachment and cataracts. A genetic test is available.

History: This disorder was characterized in the Labrador retriever by Farnum et al (1992) and Carrig et al (1977).

Inheritance: Obligate heterozygotes do not have skeletal lesions but may exhibit mild ocular lesions (Goldstein et al., 2010).

Mapping: CFA24

Molecular basis: The causative mutation is an insertion of a guanine residue in exon 1 in the COL3 domain of COL9A3, causing an amino acid codon frameshift and a premature stop codon. Reduced RNA expression is found in affected retinas (Goldstein et al., 2010). It is currently thought that the causative mutation leads to collagen absence or deficiency in cartilage and ocular collagen, with a larger effect in vitreous and retinal tissue than in the limbs (Goldstein et al., 2010).

Clinical features: Signs may be noticeable as early as 4 to 6 weeks of age (Carrig et al., 1997; Goldstein et al., 2010). Affected dogs have short-limbed dwarfism and vitreous dysplasia. Associated ophthalmic lesions include retinal detachment and cataracts. The forelimbs are most noticeably affected, particularly the short radius and ulna, which subsequently develop curvature with varus/valgus deformities (Carrig et al., 1997). In pups, the dome of the cranium is often pronounced and there is moderate excessive exotropic strabismus. Some, but not all, carriers have vitreal stands, focal retinal folds or plaques of retinal dysplasia.

Pathology: There is a range of ocular defects, but the most consistent findings are cortical equatorial cataracts and vitreal liquefaction (Goldstein et al, 2010). Histologic lesions in the growth plates included disorganization of cellular columns with abnormal extent of calcification, great variability in chrondrocyte shape, and premature cellular condensation in the maturation zone (Farnum et al., 1992).

Prevalence: The frequency of the causative allele in the overall Labrador retriever population is estimated at 4% (Goldstein et al., 2010).

Control: Parents and siblings of affected dogs should be tested. Breeding of affected or carrier dogs is not recommended.

Genetic testing: There is a test available to detect the causative mutation. Affected dogs are not reliably identified by clinical signs alone, so suspected dogs should be tested. Dogs having mild ocular lesions may be carriers and should be tested.

Breed: Labrador Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
COL9A3 collagen, type IX, alpha 3 Canis lupus familiaris 24 NC_006606.3 (46653400..46669183) COL9A3 Homologene, Ensembl, NCBI gene

Variants

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 required column headers

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Labrador Retriever Oculoskeletal dysplasia 1 COL9A3 insertion, small (<=20) an insertion of a guanine residue in exon 1 in the COL3 domain of COL9A3 2010 20686772

References


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.
2012 Miyadera, K., Acland, G.M., Aguirre, G.D. :
Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. Mamm Genome 23:40-61, 2012. Pubmed reference: 22065099. DOI: 10.1007/s00335-011-9361-3.
2010 Goldstein, O., Guyon, R., Kukekova, A., Kuznetsova, TN., Pearce-Kelling, SE., Johnson, J., Aguirre, GD., Acland, GM. :
COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia. Mamm Genome 21:398-408, 2010. Pubmed reference: 20686772. DOI: 10.1007/s00335-010-9276-4.
1995 Acland, G.M., Aguirre, G.D. :
Oculoskeletal dysplasias in Samoyed and Labrador retriever dogs: nonallelic disorders akin to Stickler-like syndromes affecting humans 2nd international DOGMAP meeting, Cambridge :, 1995.
1992 Farnum, C.E., Jones, K., Riis, R., Wilsman, N.J. :
Ocular-Chondrodysplasia in Labrador Retriever Dogs - A Morphometric and Electron Microscopical Analysis Calcified Tissue International 50:564-572, 1992. Pubmed reference: 1525714.
1988 Carrig, CB., Sponenberg, DP., Schmidt, GM., Tvedten, HW. :
Inheritance of associated ocular and skeletal dysplasia in Labrador retrievers. J Am Vet Med Assoc 193:1269-72, 1988. Pubmed reference: 3204050.
1977 Carrig, C.B., MacMillian, A., Brundage, S., Pool, R.R., Morgan, J.P. :
Retinal dysplasia associated with skeletal abnormalities in Labrador Retrievers Journal of the American Veterinary Medical Association 170:49-57, 1977. Pubmed reference: 830631.

Edit History


  • Created by Frank Nicholas on 02 Nov 2010
  • Changed by Vicki Meyers-Wallen on 13 Sep 2011
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 08 Dec 2011
  • Changed by Frank Nicholas on 12 Dec 2011