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

In other species: domestic cat , taurine cattle , sheep

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 225410 (trait) , 604539 (gene)

Links to relevant human diseases in MONDO:

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 (Dog) (VBO_0200014), Catahoula Leopard Dog (Dog) (VBO_0200298), Doberman Pinscher (Dog) (VBO_0200442), obsolete Pit Bull Terrier (Dog) (VBO_0201022).
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
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 Year Published PubMed ID(s) Acknowledgements
1513 Alapaha Blue Blood Bulldog (Dog) obsolete Pit Bull Terrier (Dog) 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 (Dog) 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 Dog (Dog) 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

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:000328-9615: 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.

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.

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
  • Changed by Imke Tammen2 on 16 Dec 2022