In other species: dog

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: 2018

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

Species-specific symbol: cEDS, EDS

Species-specific description: 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].

Molecular basis: By analysing the sequence of comparative functional candidate genes in "a 1.5-year-old, spayed female, domestic shorthair cat with EDS [Ehlers-Danlos syndrome]", Spycher et al. (2018) identified "a heterozygous single base-pair deletion in exon 43 of the COL5A1 gene, namely c.3420delG. The deletion was predicted to result in a frameshift and premature stop codon: p.(Leu1141SerfsTer134). Sanger sequencing confirmed that the variant was present in the affected cat and absent from 103 unaffected cats from different breeds. The variant was also absent from a Burmese cat with EDS. Based on knowledge about the functional impact of COL5A1 variants in other species, COL5A1:c.3420delG represents a compelling candidate causative variant for the observed EDS in the affected cat". Kiener et al. (2022) identified three additional COL5A1 loss-of-function variants in cats with cEDS using whole genome sequence data. The authors genotyped both parents of one case and experimentally confirmed the de novo mutation event leading to the dominant cEDS allele. Kiener et al. postulated de novo mutation events also for the other two variants reported in their study. McElroy et al. (2023) identified a "a novel splice acceptor site variant at exon 4 in COL5A1 (c.501-2A>C)" in a 14 week old male domestic medium hair cat with Ehlers-Danlos syndrome.
Rietmann et al. (2024) reported a female Maine Coon cat with suspected EDS diagnosis based on clinical and histopathological presentation. The authors identified a "heterozygous deletion spanning 33 740 base pairs [NC_058380.1:g.93561989_93595728del] including the last two exons of COL5A1" as likely causal variant.

Clinical features: Spycher et al. (2018): "The affected cat showed multiple recurrent skin tears with little or no bleeding, located mainly on the dorsal neck and the shoulders, and hyperextensibility of the skin (Fig. 1). The skin extensibility index, according to Hansen et al. (2015), was 27%. Some of the previous lacerations had slowly healed leaving shiny alopecic scars. Other clinical findings included bilateral hip subluxation with a positive Ortolani sign even in the awake patient, bilateral carpal hyperextension with plantigrade appearance, pain and laxity during palpation of all joints and bilateral perineal hernias. The index cat was found on the street when she was a kitten together with a female littermate, which appeared to be normal at the clinical examination."

Breeds: Bengal (Cat) (VBO_0100040), Bombay (Cat) (VBO_0100045), Domestic Shorthair, Maine Coon (Cat) (VBO_0100154).
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: