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

In other species: domestic cat

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 130000 (trait) , 120215 (gene)

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).

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 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 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

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.
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.

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