{"doi":"10.1160/th07-05-0347","title":"A novel von Willebrand factor mutation (I1372S) associated with type 2B-like von Willebrand disease: An elusive phenotype and a difficult diagnosis","abstract":"<jats:title>Summary</jats:title><jats:p>Mutations in the A1 domain of von Willebrand factor (VWF) may be associated with gain of function in theVWF-platelet GPIb interaction and consumption of largeVWF multimers, as seen in type 2B von Willebrand disease (VWD). We report a new VWF abnormality associated with greater VWF-GPIb interaction in the presence of all VWF multimers. The index case is a woman with a lifelong history of bleeding, found hyperresponsive to ristocetin with spontaneous platelet aggregation (SPA). She had normal factor VIII,VWF:Ag,VWF:RCo and VWF:CB levels, normal VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios, and a full panel of plasma and platelet VWF multimers. A missense mutation (4115T&gt;G) was found in exon 28 of theVWF gene, which replaced a isoleucine with a serine at position 1372 of pre-pro-VWF (I1372S) at heterozygous level. Recombinant VWF carrying the I1372S mutation and showing a normal VWF multimer organisation was capable of inducing SPA on normal plateletrich plasma (unlike wild-type VWF), as well as a hyper-response to ristocetin in the same platelets (0.6 mg/ml ristocetin vs. 1.2 of wild-type VWF). The new I1372S VWF mutation, characterised by SPA and hyper-responsiveness to ristocetin thus has some of the features of type 2B VWD, but not the lack of large VWF multimers, so we defined this variant as type 2B-likeVWD. Why I1372SVWF is associated with bleeding symptoms, despite normalVWF levels and multimer organisation,remains to be seen.</jats:p>","journal":"Thrombosis and Haemostasis","year":2007,"id":33022,"datarank":1.163737952361636,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.7000815843578885,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.7000815843578885,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":15,"citers_with_citation_signal":13,"citers_with_endowment":13,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":173675,"name":"Elena Pontara","orcid":null,"position":1,"is_corresponding":false},{"id":173676,"name":"Lisa Gallinaro","orcid":null,"position":2,"is_corresponding":false},{"id":173677,"name":"Antonella Bertomoro","orcid":null,"position":3,"is_corresponding":false},{"id":173678,"name":"Maria Grazia Cattini","orcid":null,"position":4,"is_corresponding":false},{"id":173679,"name":"Viviana Daidone","orcid":null,"position":5,"is_corresponding":false},{"id":173680,"name":"Maryta Szukowska","orcid":null,"position":6,"is_corresponding":false},{"id":173681,"name":"Antonio Pagnan","orcid":null,"position":7,"is_corresponding":false},{"id":173682,"name":"Alessandra Casonato","orcid":null,"position":8,"is_corresponding":false},{"id":173674,"name":"Francesca Sartorello","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18064311","pmcid":null,"openalex_id":"https://openalex.org/W2054174072","authors":[],"funders":[{"funder_name":"Telethon Foundation and MURST","grant_id":"","title":null}],"total_grants":1,"fwci":1.1034,"citation_percentile":0.77303071,"influential_citations":1,"citation_trend":[{"year":2012,"count":2},{"year":2014,"count":2},{"year":2015,"count":2},{"year":2016,"count":4},{"year":2017,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://www.thieme-connect.de/products/ejournals/pdf/10.1160/TH07-05-0347.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1160/th07-05-0347","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18064311","host_type":"repository"},{"url":"http://hdl.handle.net/11577/2462074","host_type":"repository"}],"fields_of_study":["Platelet Disorders and Treatments","Antiplatelet Therapy and Cardiovascular Diseases","Heparin-Induced Thrombocytopenia and Thrombosis","Chemistry","Medicine","Adult","Animals","Blood Platelets","Cell Line","Cricetinae","DNA Mutational Analysis","Exons","Female","Genotype","Hemorrhage","Humans","Mutation, Missense","Pedigree","Phenotype","Platelet Aggregation","Platelet Function Tests","Platelet Glycoprotein GPIb-IX Complex","Protein Structure, Quaternary","Protein Structure, Tertiary","Ristocetin","Transfection","von Willebrand Diseases","von Willebrand Factor"],"mesh_terms":["Adult","Animals","Blood Platelets","Cell Line","DNA Mutational Analysis","Exons","Female","Genotype","Cricetinae","Hemorrhage","Humans","Pedigree","Phenotype","Platelet Aggregation","Platelet Function Tests","Ristocetin","Transfection","von Willebrand Factor","von Willebrand Diseases","Protein Structure, Tertiary","Platelet Glycoprotein GPIb-IX Complex","Mutation, Missense","Protein Structure, Quaternary"],"keywords":["Ristocetin","Von Willebrand disease","Von Willebrand factor","Platelet","Missense mutation","Mutation","Platelet Glycoprotein GPIb-IX Complex","Internal medicine","Endocrinology","Medicine","Chemistry","Molecular biology","Gene","Biology","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T15:23:32.310469Z","pmid":null,"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":[]}