OMIA:002165-9615 : classical Ehlers-Danlos syndrome (cEDS), COL5A1-related in Canis lupus familiaris
In other species: domestic cat
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: 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."
Clinical features: "On physical examination, evidence of generalized joint hyperextensibility with a range of motion greater than 180° (Figure 1) and skin hyperextensibility (Figure 2 and Figure 3) 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).
|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|
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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|
|1124||Labrador Retriever||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|
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.
|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:, 2019. Pubmed reference: 31546637 . DOI: 10.3390/genes10100731.|
- 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