Osteogenesis Imperfecta, OI (Beagle type)

Gene: COL1A2

Transmission: Autosomal dominant

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutations: 

Beagle mutation: Deletion-insertion, COL1A2 gene; c.3656_365 del-ins TGTCATTGG, p.(L1286C fs STOP 31)

Chow-Chow mutation: Substitution, COL1A2 gene; c.336+1 G>A (splicing error)

Lagotto Romagnolo mutation: Insertion (duplication), COL1A2 gene; c.877_879 dup, p.(P293 dup P)

Medical system: Skeletal

Breeds : Beagle, Chow Chow, Lagotto Romagnolo

Age at onset of clinical signs: 3 to 4 weeks

Osteogenesis imperfecta is a genetic disease caused by a defect in the synthesis of collagen, a structural protein making up bones and ligaments.  Mutations in the COL1A2 gene produce an autosomal dominant disease that is evident in puppies within the first few weeks of birth.  Affected puppies suffer from pain and lameness and have loose joints and brittle teeth.  Their bones are thin and fragile and fracture easily and heal poorly, especially the long bones and ribs.  Affected puppies do not survive to reproductive age, such that the mutations observed are incidental and self limiting for the breeds mentioned.

References:

OMIA link: [2112-9615]

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]

Letko A, Zdora I, Hitzler V, et al. (2019) A de novo in-frame duplication in the COL1A2 gene in a Lagotto Romagnolo dog with osteogenesis imperfecta. Anim Genet 50(6):786-787.  [pubmed/31468557]

Quist EM, Doan R, Pool RR, et al. (2018) Identification of a candidate mutation in the COL1A2 gene of a Chow Chow with osteogenesis imperfecta. J Hered 109:308-314.  [pubmed/29036614]

Campbell BG, Wootton JA, Macleod JN, Minor RR. (2001) Canine COL1A2 mutation resulting in C-terminal truncation of pro-alpha2(I) and severe osteogenesis imperfecta. J Bone Miner Res. 16(6):1147-53. [pubmed/11393792]