Osteochondrodysplasia (Scottish Fold)

 

Gene: TRPV4

Transmission: Autosomal dominant
For a genetic disease that is autosomal dominant, the animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy. 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. Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.

Mutation: Substitution, TRPV4 gene; c.1024 G>T, p.(V342F), exon5

Breeds: Domestic Cat, Scottish Fold

Age of onset of symptoms: Ear folding becomes evident after 3 weeks; onset of osteochondrodysplasia is variable.

The Scottish Fold breed of cat is known for its unique folded ear shape due to reduced resilience of the cartilage within the ear. This is caused by a dominant mutation within the TRPV4 gene which codes for an ion channel within cartilage and bone tissue. In addition to the ear effects, this mutation can result in cartilage and bone growth defects throughout the body, including osteochondrodysplasia of the distal hindlimbs and forelimbs, stiff or shortened tails as well as progressive degenerative joint disease. Ear folding becomes evident after about 3 weeks of age. Age of onset and severity of the additional clinical signs are highly variable between animals and can be seen in both homozygous mutated (M/M) and heterozygous (M/N) animals. Cats with mild osteochondrodysplasia can be clinically normal, and severity of signs is felt to be due to additional modifier genes that are at present unidentified. In any case, the homozygous (M/M) animal should be avoided, such that fold-cats should only be bred to non-fold cats. Because of the potential of associated disease problems, the Scottish Fold breed is not recognized by European cat registries.

 

References :

OMIA link: [0319-9685]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Rorden, C. Griswold MC, Moses N, et al. (2021) Radiographical survey of osteochondrodysplasia in Scottish Fold cats caused by the TRPV4 gene variant. Hum Genet 140(11):1525-1534. [pubmed/34406467]

Takanosu M, Hattori Y. (2020) Osteochondrodysplasia in Scottish Fold cross-breed cats. J Vet Med Sci. 82(12):1769-1772. [pubmed/33162427]

Gandolfi B, Alamri S, Darby WG, et al. (2016) A dominant TRPV4 variant underlies osteochondrodysplasia in Scottish fold cats. Osteoarthritis and Cartilage 24:1441-1450. [pubmed/27063440]

Takanosu M, Takanosu T, Suzuki H, Suzuki K. (2008) Incomplete dominant osteochondrodysplasia in heterozygous Scottish Fold cats. J Small Anim Pract. 49(4):197-9. [pubmed/18339089]

Malik R, Allan GS, Howlett CR, Thompson DE, et al. (1999) Osteochondrodysplasia in Scottish fold cats.  Australian Veterinary Journal 77:85-92.  [pubmed/10078353]