Osteogenesis Imperfecta (COL1A2 gene, Beagle)

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a genetic disease that affects collagen production in the body. Collagen is a crucial protein that helps strengthen bones.

Symptoms

Characteristic symptoms of OI include: difficulty moving or limping, bone pain and tenderness, bone deformities, bones that fracture easily, joint laxity, dental problems. Other possible signs include hearing loss and growth retardation.

Disease Management

Currently there is no cure for OI so the focus of treatment is on managing the symptoms and improving the animal's quality of life. If you suspect that your dog may have symptoms of the disease you should consult your veterinarian for the most appropriate treatment. This may include the use of pain medications, physical therapy, and in some cases, surgery to stabilize the bones.

Genetic basis

This disease follows an autosomal dominant mode of inheritance. Autosomal dominant inheritance means that dogs only have to inherit one copy of the mutation or pathogenic variant to be at risk of developing the disease. Each puppy born to a parent carrying one copy of the mutation has a 50% chance of inheriting one copy of the mutation and being at risk for the disease. Breeding between dogs carrying genetic variants that can cause disease is not recommended, even if they do not show symptoms.

Technical report

Canine OI is associated with autosomal dominant mutations in the genes coding for the alpha1 and alpha2 subunits of collagen type 1, COL1A1 and COL1A2 respectively, and with an autosomal recessive mutation in the SERPINH1 gene, involved in collagen maturation. The disease has been observed in several breeds such as Golden Retriever, Collie, Poodle, Beagle, Norwegian Elkhound, Dachshund and Bedlington Terrier. However, OI-causing mutations have only been identified in Beagle, Golden Retriever, Dachshund and Chow Chow. The variant we study here in the COL1A2 gene is c.3656_3859delinsTGTCATTGG. This alteration results in the deletion of four nucleotides (3991-3994) and their replacement by an insertion of nine nucleotides. This results in a reading frame shift and a premature stop codon leading to a truncated COL1A2 protein. The variant was identified by Campbell et al. in Beagle dogs.

Most affected breeds

Beagle
Chow Chow

Bibliography

Campbell BG, Wootton JA, Macleod JN,et al. Canine COL1A2 mutation resulting in C-terminal truncation of pro-alpha2(I) and severe osteogenesis imperfecta. J Bone Miner Res. 2001 Jun;16(6):1147-53.

Quist EM, Doan R, Pool RR,et al. Identification of a Candidate Mutation in the COL1A2 Gene of a Chow Chow With Osteogenesis Imperfecta. J Hered. 2018 Mar 16;109(3):308-314.