OMIA:000328-9615 : Dermatosparaxis Ehlers-Danlos syndrome (dEDS), ADAMTS2-related in Canis lupus familiaris
In other species: domestic cat , cattle , sheep
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 225410 (trait) , 604539 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
Species-specific name: Dermatosparaxis Ehlers Danlos syndrome (dEDS), ADAMTS2-related; Ehlers-Danlos syndrome, type VII (Dermatosparaxis)
Species-specific symbol: dEDS; EDS
Species-specific description: This phene has been renamed from "Ehlers-Danlos syndrome, type VII (Dermatosparaxis)" to "Dermatosparaxis Ehlers-Danlos syndrome (dEDS), ADAMTS2-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 the single affected dog, followed by sequence analysis of 19 comparative functional candidate genes enabled Jaffy et al. (2019) to identify the likely causal variant as a "C-to-T transition at position 2408978 on chromosome 11. This transition is predicted to alter the ADAMTS2 transcript (ADAMTS2:c.769C>T) and encode a nonsense mutation (p.Arg257Ter)."
Jaffey et al. (2022) "report two novel, ADAMTS2 variants in DNA from EDS-affected dogs. Separate whole-genome sequences from a Pit Bull Terrier and an Alapaha Blue Blood Bulldog each contained a rare, homozygous variant (11:2280117delC, CanFam3.1), predicted to produce a frameshift in the transcript from the first coding ADAMTS2 exon (c.10delC) and a severely truncated protein product, p.(Pro4ArgfsTer175). ... The whole-genome sequence from an adult Catahoula Leopard Dog contained a homozygous ADAMTS2 missense mutation, [11:2491238G>A; p.(Arg966His)]."
Clinical features: Jaffy et al. (2019): "an 8‐week‐old male Doberman Pinscher . . . was presented to South Willamette Veterinary Clinic for evaluation of cutaneous wounds. The physical examination identified pain, hyper‐mobility and moderate effusion in the carpal, tarsal and stifle joints. In addition, bilateral ocular chemosis and elevation of the nictitating membranes were noted. The skin had several wounds in various stages of healing, and several small, atrophic scars from previous wounds that had healed by secondary intention were apparent. The ventral abdomen had a fresh linear 6‐cm‐long wound. The skin was noticeably loose and hyper‐elastic".
Jaffey et al. (2022): The clinical features of these [Pit Bull Terrier and an Alapaha Blue Blood Bulldog] dogs [with the 11:2280117delC, CanFam3.1 deletion] and 4 others with the same homozygous deletion included multifocal wounds, atrophic scars, joint hypermobility, narrowed palpebral fissures, skin hyperextensibility, and joint-associated swellings. Due to severe skin fragility, the owners of all 6 dogs elected euthanasia before the dogs reached 13 weeks of age. Cross sections of collagen fibrils in post-mortem dermal tissues from 2 of these dogs showed hieroglyphic-like figures similar to those from cases of severe dermatosparaxis in other species. ... [The Catahoula Leopard Dog with the 11:2491238G>A; p.(Arg966His) variant] exhibited multifocal wounds, atrophic scars, and joint hypermobility, but has survived for at least 9 years."
Breeds: Alapaha Blue Blood Bulldog, Catahoula leopard dogs, Doberman Pinscher, Pit Bull Terrier.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ADAMTS2||ADAM metallopeptidase with thrombospondin type 1 motif, 2||Canis lupus familiaris||11||NC_051815.1 (2257166..2480747)||ADAMTS2||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|
|1513||Alapaha Blue Blood Bulldog Pit Bull Terrier||Ehlers-Danlos syndrome, type VII (Dermatosparaxis)||ADAMTS2||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||11||g.2280117delC||c.10delC||p.(P4Rfs*175)||2022||36421833|
|1117||Doberman Pinscher||Ehlers-Danlos syndrome, type VII (Dermatosparaxis)||ADAMTS2||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||11||g.2408978C>T||c.769C>T||p.(R257*)||2019||31294848|
|1514||Catahoula leopard dogs||Ehlers-Danlos syndrome, type VII (Dermatosparaxis)||ADAMTS2||missense||Genome-editing (CRISPR-Cas9)||CanFam3.1||11||g.2491238G>A||c.2897G>A||p.(R966H)||2022||36421833|
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||Jaffey, J.A., Bullock, G., Guo, J., Mhlanga-Mutangadura, T., O'Brien, D.P., Coates, J.R., Morrissey, R., Hutchison, R., Donnelly, K.S., Cohn, L.A., Katz, M.L., Johnson, G.S. :|
|Novel homozygous ADAMTS2 variants and associated disease phenotypes in dogs with dermatosparactic Ehlers-Danlos syndrome. Genes (Basel) 13:2158, 2022. Pubmed reference: 36421833 . DOI: 10.3390/genes13112158.|
|Takeda, M., Arai, N., Koketsu, Y., Mizoguchi, Y. :|
|Factors associated with canine skin extensibility in toy poodles. J Vet Med Sci :, 2022. Pubmed reference: 35046238 . DOI: 10.1292/jvms.21-0266.|
|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||Jaffey, J.A., Bullock, G., Teplin, E., Guo, J., Villani, N.A., Mhlanga-Mutangadura, T., Schnabel, R.D., Cohn, L.A., Johnson, G.S., Jaffey, J.A., Bullock, G., Teplin, E., Guo, J., Villani, N.A., Mhlanga-Mutangadura, T., Schnabel, R.D., Cohn, L.A., Johnson, G.S. :|
|A homozygous ADAMTS2 nonsense mutation in a Doberman Pinscher dog with Ehlers Danlos syndrome and extreme skin fragility. Anim Genet 50:543-545, 2019. Pubmed reference: 31294848 . DOI: 10.1111/age.12825.|
- Created by Frank Nicholas on 21 Sep 2019
- Changed by Frank Nicholas on 21 Sep 2019
- Changed by Tosso Leeb on 02 Jun 2022
- Changed by Imke Tammen2 on 16 Dec 2022