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: