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).

Molecular basis: The likely causal variant in Labradors 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).

Stavinohova et al. (2019) reported a likely causal variant in Northern Inuit Dogs (NID) to be "a nonsense single nucleotide polymorphism [c.700C>T; p.Arg234Ter] in COL9A3".

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 likely causal variant in the overall Labrador retriever population is estimated at 4% (Goldstein et al., 2010).

Stavinohova et al. (2019): the c.700C>T "variant was genotyped in a total of 1,232 dogs. All seven affected NID [Northern Inuit Dogs] were homozygous for the variant allele (T/T), while 31/116 OSD-unaffected NID were heterozygous for the variant (C/T) and 85/116 were homozygous for the wildtype allele (C/C) . . . A subset of 56 NID unrelated at the parent level were analysed to determine an allele frequency of 0.08, estimating carrier and affected rates to be 15% and 0.6% respectively in NID. All 1,109 non-NID were C/C, suggesting the variant is rare or absent in other breeds."

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

Breeds: Labrador Retriever, Northern Inuit Dog.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
COL9A3 collagen, type IX, alpha 3 Canis lupus familiaris 24 NC_051828.1 (47526060..47541889) COL9A3 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.

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) CanFam2.0 24 g.49699850_49699851insG c.10_11insG Goldstein et al. (2010): "a 1-base insertion (guanine) in exon 1 that changes a string of four guanines (CFA24: 49,699,847–49,699,850; CanFam2) to a string of five guanines (c. 7–10 insG). This shifts the open reading frame of the putative protein, alters amino acids 4–48, and introduces a premature stop codon at codon 49 (p.A4GX46)" 200922: to render this consistent with HGVS nomenclature, I am assuming that the insertion is after the last nucleotide, i.e. g.49,699,847_49,699,850insG becomes g.49699850_49699851insG; and c. 7_10insG becomes c.10_11insG. The p. info (p.A4GX46) has been removed until it can be standardised 2010 20686772
Northern Inuit Dog Oculoskeletal dysplasia 1 COL9A3 nonsense (stop-gain) CanFam3.1 24 g.46660067C>T c.700C>T p.Arg234Ter 2019 31415586


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.
2020 Sebbag, L., Riggs, A., Carnevale, J. :
Oculo-skeletal dysplasia in five Labrador Retrievers. Vet Ophthalmol 23:386-393, 2020. Pubmed reference: 31595625. DOI: 10.1111/vop.12715.
2019 Stavinohova, R., Hartley, C., Burmeister, L.M., Ricketts, S.L., Pettitt, L., Tetas Pont, R., Hitti, R.J., Schofield, E., Oliver, J.A.C., Mellersh, C.S. :
Clinical, histopathological and genetic characterisation of oculoskeletal dysplasia in the Northern Inuit Dog. PLoS One 14:e0220761, 2019. Pubmed reference: 31415586. DOI: 10.1371/journal.pone.0220761.
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.

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  • Created by Frank Nicholas on 02 Nov 2010
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  • Changed by Frank Nicholas on 28 Sep 2011
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