Chondrodysplasia, disproportionate short-limbed

Gene: ITGA10

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, ITGA10 gene; c.2083 C>T, p.(R695 STOP)

Medical system: Skeleton

Breeds: American Staffordshire Terrier/Amstaff, Boston Terrier, Boxer, Chinook, German Shepherd, Karelian Bear Dog, Labrador Retriever, Norwegian Elkhound

Age of onset of symptoms: Radiographic signs are evident from 5-12 weeks of age. Visible clinical signs are apparent from the puppy’s late development.

Chondrodysplasia as seen in the Norwegian Grey Elkhound and Karelian Bear Dog breeds is a genetic disorder of cartilage development of long bones resulting in disproportionate dwarfism.  A substitution mutation within the ITGA10 gene causes a premature stop and defective synthesis of an integrin protein on the surface of chondrocytes. This  integrin protein is essential for normal collagen binding and proper epiphyseal cartilage development within long bones.  Affected dogs, with two copies of the mutated ITGA10 gene, have a defect in collagen syntheses resulting in disordered growth and proliferation of epiphyseal cartilage.  Clinically these animals present with shortened limbs and vertebrae and often also have enlarged bones of the skull.  In a recent survey study by Donner et al. (2023), low levels of this mutation were also detected in additional dog breeds.

References:

OMIA link: [1886-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Kyöstilä K, Lappalainen AK, Lohi H. (2013) Canine chondrodysplasia caused by a truncating mutation in collagen-binding integrin alpha subunit 10. PLoS One 8:e75621.  [pubmed/24086591]

Bingel SA, Sande RD. (1982) Chondrodysplasia in the Norwegian Elkhound American Journal of Pathology 107(2):219-29. [pubmed/7081383]

Contributed by: Sydney King et Syrah Deraspe, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).