OMIA:002165-9685 : classical Ehlers-Danlos syndrome (cEDS), COL5A1-related in Felis catus (domestic cat)

In other species: dog

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 130000 (trait) , 120215 (gene)

Links to relevant human diseases in MONDO:

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. McElroy et al. (2023) identified a "a novel splice acceptor site variant at exon 4 in COL5A1 (c.501-2A>C)" in a 14 week old male domestic medium hair cat with Ehlers-Danlos syndrome.
Rietmann et al. (2024) reported a female Maine Coon cat with suspected EDS diagnosis based on clinical and histopathological presentation. The authors identified a "heterozygous deletion spanning 33 740 base pairs [NC_058380.1:g.93561989_93595728del] including the last two exons of COL5A1" as likely causal variant.

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, Maine Coon (Cat) (VBO_0100154).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

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

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 Year Published PubMed ID(s) Acknowledgements
1696 Maine Coon (Cat) classical Ehlers-Danlos syndrome COL5A1 deletion, gross (>20) Naturally occurring variant F.catus_Fcat126_mat1.0 D4 NC_058380.1:g.93561989_93595728del deletion of 33740 base pairs including the last two exons of COL5A1 2024 38745376
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 classical Ehlers-Danlos syndrome 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
1609 Domestic medium-haired classical Ehlers-Danlos syndrome COL5A1 splicing Naturally occurring variant Felis_catus_9.0 D4 g.93290016T>G c.501-2A>C XM_023242950.1 2023 37594181
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

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:002165-9685: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2024 Rietmann, S.J., Nowell, S., Keating, M.K., Bauer, C., Jagannathan, V., Leeb, T. :
Heterozygous COL5A1 deletion in a cat with classical Ehlers-Danlos syndrome. Anim Genet , 2024. Pubmed reference: 38745376. DOI: 10.1111/age.13446.
2023 McElroy, A., Gray-Edwards, H., Coghill, L.M., Lyons, L.A. :
Precision medicine using whole genome sequencing in a cat identifies a novel COL5A1 variant for classical Ehlers-Danlos syndrome. J Vet Intern Med , 2023. Pubmed reference: 37594181. DOI: 10.1111/jvim.16805.
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.

Edit History


  • Created by Frank Nicholas on 11 Feb 2019
  • Changed by Frank Nicholas on 11 Feb 2019
  • Changed by Tosso Leeb on 02 Jun 2022
  • Changed by Tosso Leeb on 27 Jun 2022
  • Changed by Imke Tammen2 on 21 Aug 2023
  • Changed by Imke Tammen2 on 17 May 2024