{"doi":"10.1111/jvim.17180","title":"Novel <i>COL5A1</i> variants and associated disease phenotypes in dogs with classical Ehlers-Danlos syndrome","abstract":"BACKGROUND: Human patients with Ehlers-Danlos syndrome (EDS) are categorized into subtypes based on causative genetic variants and phenotypes. The classical form of EDS, primarily caused by variants in COL5A1 or COL5A2, is a very common subtype in people but is poorly characterized in dogs. OBJECTIVE: Describe likely causal COL5A1 variants in dogs with classical EDS, summarize clinical histories, discuss potential disease mechanisms, and draw conclusions about disease prognosis. ANIMALS: Seven client-owned dogs that exhibited clinical signs of classical EDS. METHODS: Clinical information was recorded from medical records and communication with attending veterinarians and dog owners. To identify potential causal gene sequence variants whole-genome sequence analyses (n = 6) or Sanger sequencing (n = 1) were performed on DNA isolated from the probands. Pathological abnormalities in skin biopsy samples were assessed using histology and electron microscopy in 3 dogs. RESULTS: Six distinct heterozygous COL5A1 sequence variants were identified. 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. CONCLUSION AND CLINICAL IMPORTANCE: We describe the genotypic and phenotypic spectrum of the classical subtype of EDS by identifying 6 novel COL5A1 variants in conjunction with detailed clinical histories that included long-term follow-up information in 7 dogs.","journal":"Journal of Veterinary Internal Medicine","year":2024,"id":479028,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":452825,"name":"Jared A. Jaffey","orcid":"0000-0002-0270-4728","position":1,"is_corresponding":false},{"id":452830,"name":"Leah A. Cohn","orcid":"0000-0002-7785-2696","position":2,"is_corresponding":false},{"id":1318331,"name":"Erika Sox","orcid":null,"position":3,"is_corresponding":false},{"id":451754,"name":"Eric T. Hostnik","orcid":"0000-0002-7651-4775","position":4,"is_corresponding":false},{"id":1318332,"name":"Kyle D. Hutcheson","orcid":null,"position":5,"is_corresponding":false},{"id":1318333,"name":"Erin Matero","orcid":null,"position":6,"is_corresponding":false},{"id":1318334,"name":"Karen S. Hoffmann","orcid":null,"position":7,"is_corresponding":false},{"id":414484,"name":"Gary S. Johnson","orcid":"0000-0003-2225-3204","position":8,"is_corresponding":false},{"id":400492,"name":"Martin L. Katz","orcid":"0000-0002-2582-9187","position":9,"is_corresponding":false},{"id":452828,"name":"Garrett Bullock","orcid":"0000-0002-9231-8758","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:06:50.355747Z","pmid":"39175162","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}