OMIA 000319-9685 : Ears, folded (drop vs prick) in Felis catus

In other species: dog , pig , sheep

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 113500 (trait) , 606835 (trait) , 606071 (trait) , 156530 (trait) , 168400 (trait) , 181405 (trait) , 184095 (trait) , 600175 (trait) , 184252 (trait) , 605427 (gene) , 613719 (gene) , 613718 (trait) , 617383 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Incompletely Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific name: Scottish fold, Scottish Fold osteochondrodysplasia(SFOCD), osteodystrophy

Species-specific description: This entry combines information about two phenes in cats: 'OMIA000319-9685 : Ears folded (drop vs prick)' and 'OMIA001315-9685 : Osteochondrodysplasia' as both are caused by the same mutation.

Inheritance: Data supporting incompletely penetrant autosomal dominant inheritance was reported by Todd (1972), Dyte and Turner (1973) and Takanosu et al. (2008).

Mapping: By conducting a case-control GWAS on "35 Scottish fold and 32 controls (17 Scottish Shorthair, 8 Selkirk Rex, 3 British Shorthair and 4 Persian)", each genotyped with the Illumina Infinium Feline 63K iSelect DNA chip (yielding 46,203 informative SNPs), Gandolfi et al. (2016) mapped this disorder to a region of chromosome FCAD3 from D3:24,380,099 bp to D3:25,202,262 bp.

Molecular basis: Of the 23 genes in the mapped region (see above), Gandolfi et al. (2016) identified the most likely candidate as TPRV4. mutations in which are "responsible for a spectrum of dominantly inherited human skeletal dysplasias" (see Possible human homologues above). Sequencing of the coding sequence of this gene in 2 affecteds and 3 controls, followed by direct sequencing in other cats revealed just one missense mutation (c.1024G>T; p.V342F) as the likely cause: "all 21 Scottish shorthair cats were homozygous for the wild-type allele, two Scottish fold cats were homozygous for the variant allele and 39 Scottish fold cats were heterozygous. A single Scottish fold cat tested homozygous wild-type". Further "Screening of 648 cats representing several breeds and domestic shorthair cats of unknown ear type demonstrated the c.1024G>T substitution was detected only in the Scottish fold breed and was absent in all other populations."

Clinical features: As summarised by Gandolfi et al. (2016), "Scottish fold cats, named for their unique ear shape, have a dominantly inherited osteochondrodysplasia involving malformation in the distal forelimbs, distal hindlimbs and tail, and progressive joint destruction."

Rorden et al. (2021) "early work demonstrated that homozygous cats with two copies of this variant develop severe radiographic consequences. Subsequent breeding programs have mated heterozygous cats with straight-eared cats to ensure an equal mix of heterozygous (fold) and wild-type (nonfolded) offspring, in the hope of raising healthy cats. More recent radiological surveys suggest that these heterozygous cats may also have medical problems consisting of deformed distal extremities in the worst cases and accelerated onset of osteoarthritis. … Our aim was to determine if heterozygous cats exhibit radiological abnormalities…. Specifically, DNA and radiographs were acquired for 22 Scottish Fold cats. Four reviewers, blinded to the ear phenotype, assessed the lateral radiographs. … Although each reviewer, on average, gave a numerically worse 'severity score' to folded-ear cats relative to straight-ear cats, the images in heterozygous cats showed much milder radiological signs than previously published.”

Pathology: Gandolfi et al. (2016): "Preliminary histologic examinations suggested chondrocyte cell death in articular cartilage, and disturbed maturation of proliferative chondrocytes to hypertrophic chondrocytes in the growth plate [Malik et al., 1999]."

Endochondral ossification of tail bones, carpal, metacarpal, tarsal and metatarsal bones are observed in affected animals. Joint inflammation results from the joint fusion, and exostoses (benign bone growths) may also occur (Rorden et al., 2020).

[IT thanks DVM students Beverly Hwang and Grace Iacobbe for contributions to this entry in April 2022]

Breeds: Foldex, Highland Fold, Scottish Fold.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TRPV4 transient receptor potential cation channel, subfamily V, member 4 Felis catus D3 NC_058379.1 (18746862..18711473) TRPV4 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
140 Scottish Fold Ears, folded TRPV4 Fd missense Naturally occurring variant Felis_catus_9.0 D3 g.18884219C>A c.1024G>T p.(V342F) XM_023241517.1; XP_023097285.1 2016 27063440 Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley.

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2022 Sartore, S., Moretti, R., Iamone, G., Piras, L.A., Chessa, S., Sacchi, P. :
Short Communication: Ligase Detection Reaction as a genotyping technique to identify cats carrying the c.1024G>T mutation on TRPV4 gene. Research Square :, 2022. DOI: 10.21203/rs.3.rs-1380903/v1.
2021 Alhaddad, H., Abdi, M., Lyons, L.A. :
Patterns of allele frequency differences among domestic cat breeds assessed by a 63K SNP array. PLoS One 16:e0247092, 2021. Pubmed reference: 33630878. DOI: 10.1371/journal.pone.0247092.
Rorden, C., Griswold, M.C., Moses, N., Berry, C.R., Keller, G.G., Rivas, R., Flores-Smith, H., Shaffer, L.G., Malik, R. :
Radiographical survey of osteochondrodysplasia in Scottish Fold cats caused by the TRPV4 gene variant. Hum Genet 140:1525-1534, 2021. Pubmed reference: 34406467. DOI: 10.1007/s00439-021-02337-5.
2020 Nakajo, T., Fujita, Y., Ichinohe, T., Maruo, T. :
Combined surgical, radiation, and medical therapies for osteochondrodysplasia in a Scottish Fold cat. J Am Anim Hosp Assoc 56:175, 2020. Pubmed reference: 32182117. DOI: 10.5326/JAAHA-MS-6980.
Takanosu, M., Hattori, Y. :
Osteochondrodysplasia in Scottish Fold cross-breed cats. J Vet Med Sci 82:1769-1772, 2020. Pubmed reference: 33162427. DOI: 10.1292/jvms.20-0299.
2019 Selting, K.A., Lattimer, J.C., Hause, W., Megan, G. :
Osteochondrodysplasia in a Scottish Fold cat treated with radiation therapy and samarium-153-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid. J Am Anim Hosp Assoc 55:e55304, 2019. Pubmed reference: 30870611. DOI: 10.5326/JAAHA-MS-6797.
2016 Gandolfi, B., Alamri, S., Darby, W.G., Adhikari, B., Lattimer, J.C., Malik, R., Wade, C.M., Lyons, L.A., Cheng, J., Bateman, J.F., McIntyre, P., Lamandé, S.R., Haase, B. :
A dominant TRPV4 variant underlies osteochondrodysplasia in Scottish fold cats. Osteoarthritis Cartilage 24:1441-50, 2016. Pubmed reference: 27063440. DOI: 10.1016/j.joca.2016.03.019.
2015 Fujiwara-Igarashi, A., Igarashi, H., Hasegawa, D., Fujita, M. :
Efficacy and complications of palliative irradiation in three Scottish Fold cats with osteochondrodysplasia. J Vet Intern Med 29:1643-7, 2015. Pubmed reference: 26365740. DOI: 10.1111/jvim.13614.
2009 Nagai, A., Fujioka, T., Ebata, K., Ishihara, N., Setobayashi, M., Fujioka, S., Miyake, R. :
The radiotherapy of osteochondorodysplasia in a Scottish Fold cat Japanese Journal of Veterinary Anesthesia & Surgery 40:13-17, 2009.
2008 Takanosu, M., Takanosu, T., Suzuki, H., Suzuki, K. :
Incomplete dominant osteochondrodysplasia in heterozygous Scottish Fold cats. J Small Anim Pract 49:197-9, 2008. Pubmed reference: 18339089. DOI: 10.1111/j.1748-5827.2008.00561.x.
2007 Chang, J., Jung, J., Oh, S., Lee, S., Kim, G., Kim, H., Kweon, O., Yoon, J., Choi, M. :
Osteochondrodysplasia in three Scottish Fold cats. J Vet Sci 8:307-9, 2007. Pubmed reference: 17679781. DOI: 10.4142/jvs.2007.8.3.307.
2004 Hubler, M., Volkert, M., Kaser-Hotz, B., Arnold, S. :
Palliative irradiation of Scottish Fold osteochondrodysplasia. Vet Radiol Ultrasound 45:582-5, 2004. Pubmed reference: 15605854. DOI: 10.1111/j.1740-8261.2004.04101.x.
2002 Schrey, C., Gerlach, K.F. :
Osteochondrodysplasia in poodle cats (Rex Fold) Kleintierpraxis 47:433-435, 2002.
2000 Simon, D. :
Osteochondrodystrophy in the Scottish fold cat Tierarztliche Praxis Ausgabe Kleintiere Heimtiere 28:86+, 2000.
1999 Malik, R., Allan, G.S., Howlett, C.R., Thompson, D.E., James, G., McWhirter, C., Kendall, K. :
Osteochondrodysplasia in Scottish Fold cats Australian Veterinary Journal 77:85-92, 1999. Pubmed reference: 10078353. DOI: 10.1111/j.1751-0813.1999.tb11672.x.
1998 Vecchiotti, G.G :
Two breeds of cats with ear mutations (American Curl and Scottish Fold) Praxis Veterinaria (Milano) 19:25-27, 1998.
1996 Partington, BP., Williams, JF., Pechman, RD., Beach, RT. :
What is your diagnosis? Scottish Fold osteodystrophy. J Am Vet Med Assoc 209:1235-6, 1996. Pubmed reference: 8837640.
1995 Mathews, K.G., Koblik, P.D., Knoeckel, M.J., Pool, R.R., Fyfe, J.C. :
Resolution of lameness associated with Scottish fold osteodystrophy following bilateral ostectomies and pantarsal arthrodeses Journal of the American Animal Hospital Association 31:280-288, 1995. Pubmed reference: 7552658.
1975 Jackson, O.F. :
Congenital bone lesions in cats with folded ears Bulletin of the Feline Advisory Bureau 14:2-4, 1975.
1973 Dyte, C.E., Turner, P. :
Further data on folded-ear cats Carnivore Genetics Newsletter 2:112 only, 1973.
1972 Todd, N.B. :
Folded-ear cats: further observations Carnivore Genetics Newsletter 2:64-65, 1972.

Edit History


  • Created by Frank Nicholas on 10 Feb 2011
  • Changed by Frank Nicholas on 13 Apr 2016
  • Changed by Imke Tammen2 on 22 Aug 2021
  • Changed by Imke Tammen2 on 22 May 2022