In other species: domestic cat

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 130000 (trait) , 120215 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0019567: Ehlers-Danlos syndrome, classic type, 1

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

Species summary: 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].

Species-specific name: classical Ehlers-Danlos syndrome (cEDS), COL5A1-related; Ehlers-Danlos syndrome, classic type, 1

Species-specific symbol: cEDS, EDS

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."
Bullock et al. (2024) "describe the genotypic and phenotypic spectrum of the classical subtype of EDS by identifying 6 novel COL5A1 variants [omia.variant:1719-1724] in conjunction with detailed clinical histories that included long-term follow-up information in 7 dogs."

Clinical features: "On physical examination, evidence of generalized joint hyperextensibility with a range of motion greater than 180° ... and skin hyperextensibility ... 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).
Bullock et al. (2024) reported 7 affected dogs from different breeds: "The most common clinical signs included fragile skin (n = 7), hyperextensible skin (n = 7), joint hypermobility (n = 6), and atrophic scars (n = 5). The median age at last follow-up or death was 12 years (range, 6.5-14 years). Ultrastructural abnormalities in dermal collagen differed among dogs with different COL5A1 variants."

Breeds: Beagle (Dog) (VBO_0200131), Dachshund, Miniature (Dog) (VBO_0200408), German Shepherd Dog (Dog) (VBO_0200577), Golden Retriever (Dog) (VBO_0200610), Labrador Retriever (Dog) (VBO_0200800), Mixed Breed (Dog) (VBO_0200902), Scottish Terrier (Dog) (VBO_0201198).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: