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:

• MONDO:0009161: Ehlers-Danlos syndrome, dermatosparaxis type

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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), American Pit Bull Terrier (Dog) (VBO_0200054), Catahoula Leopard Dog (Dog) (VBO_0200298), Doberman Pinscher (Dog) (VBO_0200442).
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: