In other species: domestic cat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 130000

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

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."

Clinical features: "On physical examination, evidence of generalized joint hyperextensibility with a range of motion greater than 180° (Figure 1) and skin hyperextensibility (Figure 2 and Figure 3) 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).

Associated gene: