OMIA 000328-9615 : Dermatosparaxis Ehlers-Danlos syndrome (dEDS), ADAMTS2-related in Canis lupus familiaris

In other species: domestic cat , cattle , sheep

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 225410 (trait) , 604539 (gene)

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)."

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".

Breed: Doberman Pinscher.

Associated gene:

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

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
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

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.
2022 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.

Edit History


  • Created by Frank Nicholas on 21 Sep 2019
  • Changed by Frank Nicholas on 21 Sep 2019
  • Changed by Tosso Leeb on 02 Jun 2022