{"doi":"10.1111/jvim.70150","title":"Identification of a Novel Mutation in the SERPINE1 Gene Causing Clinical Hyperfibrinolysis in English Springer Spaniel Dogs","abstract":"BACKGROUND: A 7-month-old female spayed English Springer Spaniel (ESS) was evaluated for spontaneous hemoperitoneum. Hyperfibrinolysis was identified on thromboelastography. HYPOTHESIS/OBJECTIVES: To identify a genetic mutation causing congenital hyperfibrinolysis in the proband and evaluate the prevalence of the mutation in the ESS breed. ANIMALS: Client-owned ESS with hemorrhage and a non-affected littermate. Samples of DNA from 3 ESS, 1 Welsh Springer Spaniel (WSS) with unexplained hemorrhage, and 199 ESS with no history of hemorrhage. METHODS: Whole genome sequencing (WGS) of the proband with variant filtering against an in-house WGS database of 671 presumably unaffected dogs identified a deleterious variant of SERPINE1 unique to the proband, which encodes for plasminogen activator inhibitor 1 (PAI-1). SERPINE1 was genotyped in the remaining animal population by Sanger sequencing or a Taqman assay. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on platelet pellets from the proband, a littermate, and three unrelated healthy ESS. RESULTS: Whole genome sequencing of the proband identified a unique homozygous insertion at chr6:8640592 in exon 1 of SERPINE1, which is predicted to cause a premature stop codon. The unaffected littermate was heterozygous for the mutation. Two unrelated ESS and 1 WSS with post-operative hemorrhage were homozygous for the mutation. Absence of PAI-1 in the proband's platelets was documented using LC-MS/MS. CONCLUSIONS AND CLINICAL IMPORTANCE: This novel mutation in SERPINE1 is associated with the absence of the PAI-1 protein in platelets and might cause hemorrhage because of hyperfibrinolysis in ESS and related breeds.","journal":"Journal of Veterinary Internal Medicine","year":2025,"id":553066,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9322,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":766974,"name":"Jonah N. Cullen","orcid":"0000-0001-5144-8524","position":1,"is_corresponding":false},{"id":1416325,"name":"Farah F. Almeer","orcid":null,"position":2,"is_corresponding":false},{"id":296490,"name":"LeeAnn Higgins","orcid":null,"position":3,"is_corresponding":false},{"id":294204,"name":"Todd W. Markowski","orcid":"0000-0001-9157-2036","position":4,"is_corresponding":false},{"id":449154,"name":"Marjory B. Brooks","orcid":"0000-0001-5489-9013","position":5,"is_corresponding":false},{"id":383124,"name":"Steven G. Friedenberg","orcid":"0000-0002-7510-2322","position":6,"is_corresponding":false},{"id":1449384,"name":"Molly A. Racette","orcid":"0000-0003-1321-2195","position":7,"is_corresponding":false},{"id":1449383,"name":"Kelley Kilpatrick","orcid":"0000-0003-2137-6560","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:54:37.527189Z","pmid":"40470612","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":[]}