OMIA:002165-9685 : classical Ehlers-Danlos syndrome (cEDS), COL5A1-related in Felis catus
In other species: dog
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 130000 (trait) , 120215 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2018
Species-specific name: classical Ehlers-Danlos syndrome (cEDS), COL5A1-related; Ehlers-Danlos syndrome, classic type, 1
Species-specific symbol: cEDS, EDS
Species-specific description: This phene has been renamed from "Ehlers-Danlos syndrome, classic type, 1" to "classical Ehlers-Danlos syndrome (cEDS), COL5A1-related" in OMIA on the basis of the review on human Ehlers-Danlos syndromes by Malfait et al. (2020) [2/6/2022].
Molecular basis: By analysing the sequence of comparative functional candidate genes in "a 1.5-year-old, spayed female, domestic shorthair cat with EDS [Ehlers-Danlos syndrome]", Spycher et al. (2018) identified "a heterozygous single base-pair deletion in exon 43 of the COL5A1 gene, namely c.3420delG. The deletion was predicted to result in a frameshift and premature stop codon: p.(Leu1141SerfsTer134). Sanger sequencing confirmed that the variant was present in the affected cat and absent from 103 unaffected cats from different breeds. The variant was also absent from a Burmese cat with EDS. Based on knowledge about the functional impact of COL5A1 variants in other species, COL5A1:c.3420delG represents a compelling candidate causative variant for the observed EDS in the affected cat".
Kiener et al. (2022) identified three additional COL5A1 loss-of-function variants in cats with cEDS using whole genome sequence data. The authors genotyped both parents of one case and experimentally confirmed the de novo mutation event leading to the dominant cEDS allele. Kiener et al. postulated de novo mutation events also for the other two variants reported in their study.
Clinical features: Spycher et al. (2018): "The affected cat showed multiple recurrent skin tears with little or no bleeding, located mainly on the dorsal neck and the shoulders, and hyperextensibility of the skin (Fig. 1). The skin extensibility index, according to Hansen et al. (2015), was 27%. Some of the previous lacerations had slowly healed leaving shiny alopecic scars. Other clinical findings included bilateral hip subluxation with a positive Ortolani sign even in the awake patient, bilateral carpal hyperextension with plantigrade appearance, pain and laxity during palpation of all joints and bilateral perineal hernias. The index cat was found on the street when she was a kitten together with a female littermate, which appeared to be normal at the clinical examination."
Breeds: Bengal (Cat) (VBO_0100040), Bombay (Cat) (VBO_0100045), Domestic Shorthair.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|COL5A1||collagen, type V, alpha 1||Felis catus||D4||NC_058380.1 (93735906..93587273)||COL5A1||Homologene, Ensembl , NCBI gene|
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
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|
|1465||Bombay (Cat)||classical Ehlers-Danlos syndrome||COL5A1||nonsense (stop-gain)||Naturally occurring variant||Felis_catus_9.0||D4||g.93209345T>A||c.3514A>T||p.(Lys1172*)||XM_023242950.1; XP_023098718.1||2022||35627182|
|1025||Domestic Shorthair||Ehlers-Danlos syndrome, classic type, 1||COL5A1||deletion, small (<=20)||Naturally occurring variant||Felis_catus_9.0||D4||g.93210344del||c.3420del||p.(L1141Sfs*134)||XM_023242951.1; XP_023098719.1; published as c.3420delG||2018||30246406|
|1466||Domestic Shorthair||classical Ehlers-Danlos syndrome||COL5A1||deletion, small (<=20)||Naturally occurring variant||Felis_catus_9.0||D4||g.93215496del||c.3066del||p.(Gly1023Valfs*50)||XM_023242950.1; XP_023098718.1||2022||35627182|
|1464||Bengal (Cat)||classical Ehlers-Danlos syndrome||COL5A1||deletion, gross (>20)||Naturally occurring variant||Felis_catus_9.0||D4||g.93331577_93331598del||c.112_118+15del||r.spl?||XM_023242950.1||2022||35627182|
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||Kiener, S., Apostolopoulos, N., Schissler, J., Hass, P.K., Leuthard, F., Jagannathan, V., Schuppisser, C., Soto, S., Welle, M., Mayer, U., Leeb, T., Fischer, N.M., Kaessmeyer, S. :|
|Independent COL5A1 variants in cats with Ehlers-Danlos syndrome. Genes (Basel) 13:797, 2022. Pubmed reference: 35627182 . DOI: 10.3390/genes13050797.|
|2021||Roberts, J.H., Halper, J. :|
|Connective tissue disorders in domestic animals. Adv Exp Med Biol 1348:325-335, 2021. Pubmed reference: 34807427 . DOI: 10.1007/978-3-030-80614-9_15.|
|Vroman, R., Malfait, A.M., Miller, R.E., Malfait, F., Syx, D. :|
|Animal models of Ehlers-Danlos syndromes: Phenotype, pathogenesis, and translational potential. Front Genet 12:726474, 2021. Pubmed reference: 34712265 . DOI: 10.3389/fgene.2021.726474.|
|2020||Malfait, F., Castori, M., Francomano, C.A., Giunta, C., Kosho, T., Byers, P.H. :|
|The Ehlers-Danlos syndromes. Nat Rev Dis Primers 6:64, 2020. Pubmed reference: 32732924 . DOI: 10.1038/s41572-020-0194-9.|
|2018||Spycher, M., Bauer, A., Jagannathan, V., Frizzi, M., De Lucia, M., Leeb, T. :|
|A frameshift variant in the COL5A1 gene in a cat with Ehlers-Danlos syndrome. Anim Genet 49:641-644, 2018. Pubmed reference: 30246406 . DOI: 10.1111/age.12727.|
- Changed by Frank Nicholas on 11 Feb 2019
- Created by Frank Nicholas on 11 Feb 2019
- Changed by Tosso Leeb on 02 Jun 2022
- Changed by Tosso Leeb on 27 Jun 2022