OMIA:002165-9615 : classical Ehlers-Danlos syndrome (cEDS), COL5A1-related in Canis lupus familiaris (dog)

In other species: domestic cat

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:

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

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: "Whole-genome sequencing [of two affected dogs - one a Labrador and the other mixed-breed - by Bauer et al., 2019] revealed de novo mutations of COL5A1 in both cases, confirming the diagnosis of the classical form of EDS. The heterozygous COL5A1 p.Gly1013ValfsTer260 mutation characterized in case 1 introduced a premature termination codon and would be expected to result in α1(V) mRNA nonsense-mediated mRNA decay and collagen V haploinsufficiency. . . . In the second case, DNA sequencing demonstrated a p.Gly1571Arg missense variant in the COL5A1 gene. . . . such a glycine substitution would be expected to destabilize the strict molecular structure of the collagen V triple helix and thus affect protein stability and/or integration of the mutant collagen into the collagen V/collagen I heterotypic dermal fibrils."
Bullock et al. (2024) "describe the genotypic and phenotypic spectrum of the classical subtype of EDS by identifying 6 novel COL5A1 variants [omia.variant:1719-1724] in conjunction with detailed clinical histories that included long-term follow-up information in 7 dogs."

Clinical features: "On physical examination, evidence of generalized joint hyperextensibility with a range of motion greater than 180° ... and skin hyperextensibility ... and fragility was noted" in an affected Labrador Retriever (Bauer et al. 2019). Two affected mixed breed dogs also showed marked skin hyperextensibility. Bruising and wounds were noted to occur after only mild trauma in these dogs. Joint hypermobility, a typical sign for classical Ehlers-Danlos, was not investiagted in the affected mixed breed dogs (Bauer et al. 2019).
Bullock et al. (2024) reported 7 affected dogs from different breeds: "The most common clinical signs included fragile skin (n = 7), hyperextensible skin (n = 7), joint hypermobility (n = 6), and atrophic scars (n = 5). The median age at last follow-up or death was 12 years (range, 6.5-14 years). Ultrastructural abnormalities in dermal collagen differed among dogs with different COL5A1 variants."

Breeds: Beagle (Dog) (VBO_0200131), Dachshund, Miniature (Dog) (VBO_0200408), German Shepherd Dog (Dog) (VBO_0200577), Golden Retriever (Dog) (VBO_0200610), Labrador Retriever (Dog) (VBO_0200800), Mixed Breed (Dog) (VBO_0200902), Scottish Terrier (Dog) (VBO_0201198).
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 Canis lupus familiaris 9 NC_051813.1 (51583512..51733920) 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
1124 Labrador Retriever (Dog) Ehlers-Danlos syndrome, classic type, 1 COL5A1 deletion, small (<=20) Naturally occurring variant CanFam3.1 9 g.50806169del c.3038del p.(G1013Vfs*260) XM_022423936.1; XP_022279644.1; published as c.3038delG - "variant arose by a de novo mutation event during the development of the mother." (Bauer et al., 2019) 2019 31546637
1125 Mixed Breed (Dog) Ehlers-Danlos syndrome, classic type, 1 COL5A1 missense Naturally occurring variant CanFam3.1 9 g.50832936G>A c.4711G>A p.(G1571R) XM_022423936.1,c.4711G>A; XP_022279644.1,p.(Gly1571Arg) 2019 31546637
1722 Golden Retriever (Dog) Ehlers-Danlos syndrome, classic type 1 COL5A1 nonsense (stop-gain) Naturally occurring variant Dog10K_Boxer_Tasha 9 NC_006591.4:g.50091843C>T XM_038615652.1:c.2512C>T XP_038471580.1:p.(R838*) ENSCAFT00000031582.6:c.2500C>T, p.(Arg834Ter) 2024 39175162
1719 Mixed Breed (Dog) Ehlers-Danlos syndrome, classic type 1 COL5A1 deletion, small (<=20) Naturally occurring variant Dog10K_Boxer_Tasha 9 NC_006591.4:g.50109824del XM_038615652.1:c.3371del XP_038471580.1:p.(E1124Lfs*364) ENSCAFT00000031582.6:c.3360del, p.(E1121Lfs*364)  2024 39175162
1721 Dachshund, Miniature (Dog) Ehlers-Danlos syndrome, classic type 1 COL5A1 duplication Naturally occurring variant Dog10K_Boxer_Tasha 9 NC_006591.4:g.50111993dup XM_038615652.1:c.3675dup XP_038471580.1:p.(G1226Rfs*62) Published as g.50111986insC, ENSCAFT00000031582.6:c.3663_3664insC, p.(Gly1222Argfs*62). Coordinates in this table have been adjusted in accordance with the HGVS recommendations.  2024 39175162
1720 Scottish Terrier (Dog) Ehlers-Danlos syndrome, classic type 1 COL5A1 deletion, small (<=20) Naturally occurring variant Dog10K_Boxer_Tasha 9 NC_006591.4:g.50114284del XM_038615652.1:c.3908del XP_038471580.1:(P1303Rfs*186) Published as g.50114279delC; ENSCAFT00000031582.6:c.3891del; p.(P1299Rfs*186). Coordinates in this table have been adjusted in accordance with the HGVS 3'rule. 2024 39175162
1724 German Shepherd Dog (Dog) Ehlers-Danlos syndrome, classic type 1 COL5A1 missense Naturally occurring variant Dog10K_Boxer_Tasha 9 NC_006591.4:g.50116228G>A XM_038615652.1:c.4117G>A XP_038471580.1:p.(G1373R) ENSCAFT00000031582.6:c.4105G>A, p.(Gly1369Arg) 2024 39175162
1723 Beagle (Dog) Ehlers-Danlos syndrome, classic type 1 COL5A1 deletion, small (<=20) Naturally occurring variant Dog10K_Boxer_Tasha 9 NC_006591.4:g.50131170_50131172del XM_038615652.1:c.5320_5322del XP_038471580.1:p.G1774del Published as chr9:50131166delGAG, ENSCAFT00000031582.6:c.5296_5298del,  p.(Glu1766del). Coordinates in this table have been adjusted in accordance with the HGVS 3'rule.
2024 39175162

Clinical synopsis/links to phenotypes

Variant Phenotype(s) References (Pubmed ID)
Common phenotypes UPHENO:0050422: abnormal collagen fibril organization
MP:0008438: abnormal cutaneous collagen fibril morphology
HP:0001075: atrophic scar
MP:0003089: decrease skin tensile strength
HP:0001030: fragile skin
HP:0000974: hyperextensible skin
HP:0001382: joint hypermobility
MP:0030797: joint laxity
MP:0005421: loose skin
39175162

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:002165-9615: 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 Bullock, G., Jaffey, J.A., Cohn, L.A., Sox, E., Hostnik, E.T., Hutcheson, K.D., Matero, E., Hoffmann, K.S., Johnson, G.S., Katz, M.L. :
Novel COL5A1 variants and associated disease phenotypes in dogs with classical Ehlers-Danlos syndrome. J Vet Intern Med 38:2431-2443, 2024. Pubmed reference: 39175162. DOI: 10.1111/jvim.17180.
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.
2019 Bauer, A., Bateman, J.F., Lamandé, S.R., Hanssen, E., Kirejczyk, S.G.M., Yee, M., Ramiche, A., Jagannathan, V., Welle, M., Leeb, T., Bateman, F.L. :
Identification of two independent COL5A1 variants in dogs with Ehlers-Danlos syndrome. Genes (Basel) 10:731, 2019. Pubmed reference: 31546637. DOI: 10.3390/genes10100731.

Edit History


  • Created by Frank Nicholas on 26 Sep 2019
  • Changed by Frank Nicholas on 26 Sep 2019
  • Changed by Tosso Leeb on 26 Sep 2019
  • Changed by Tosso Leeb on 02 Jun 2022
  • Changed by Imke Tammen2 on 18 Jun 2024
  • Changed by Imke Tammen2 on 24 Aug 2024
  • Changed by Imke Tammen2 on 06 Sep 2024