Skeletal dysplasia

Gene: LTBP3

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: Deletion, LTBP3 gene; c.158 del. G, p.(G53A fs STOP 16), exon1, chr.D1.

Medical system: Skeletal

Breeds: British Shorthair

Age of onset of symptoms: 8 – 10 weeks

Two kittens from an inbred pedigree of British Shorthair cats showed limb paralysis, loss of motor functions of the hind limbs, lordosis and scoliosis as well as intestinal stasis.  Radiographs revealed severe vertebral column defects with compression of the spinal cord.  The kittens were euthanized for humanitarian reasons.  Molecular studies revealed a homozygous mutation in the LTBP3 gene, which codes for a protein that regulates the expression of the TGFb growth factor, which itself is involved in bone growth and remodeling. Both parents of the affected kittens were carriers for the mutation in question.  A small survey of 6 unrelated British Shorthair cats did not detect the mutation.  Due to this small sample size, it is unclear whether the mutation in the LTBP3 gene is restricted to a single pedigree or is of larger concern for the British Shorthair breed.  A survey of genomes from 430 additional cats including domestic cats and cats from breeds other than the British Shorthair breed did not detect the mutation.

References:

OMIA link: [2485-9685]

Rudd Garces G, Knebel A, Hülskötter K, et al. (2021) LTBP3 frameshift variant in British Shorthair cats with complex skeletal dysplasia. Genes (Basel) 12(12):1923.  [pm/34946872]

Contributed by: Éloïse Bonneville and Élyane Moreau, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation DWS).