{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:07:56Z","timestamp":1753862876013,"version":"3.41.2"},"reference-count":18,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070139"],"award-info":[{"award-number":["82070139"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Case Reports"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The risk factors for a family with VWD presenting with an ischemic stroke (IS) were explored. FVIII activity (FVIII:C), VWF antigen (VWF:Ag), and protein S activity were measured. Next generation sequencing (NGS) was performed targeting <jats:italic>F8<\/jats:italic>, <jats:italic>F9<\/jats:italic>, <jats:italic>VWF<\/jats:italic>, <jats:italic>PROC, and PROS1<\/jats:italic>. Sanger sequencing validation was performed on family members. The proband and his sister both had low FVIII:C (1\u00a0IU\/dL) and VWF:Ag (3\u00a0IU\/dL) levels, confirming the diagnosis of type 3 VWD. His father had nearly normal levels of FVIII:C (58\u2009IU\/dL) and VWF:Ag (57\u2009IU\/dL). His daughter had type 1 VWD with decreased FVIII:C (46\u2009IU\/dL) and VWF:Ag (19\u2009IU\/dL). NGS identified a heterozygous VWF c.2328delT (p.A778Lfs*23) frame shift mutation only in the proband and his sister. Another VWF missense mutation, c.6521G\u2009&gt;\u2009T (p.C2174F), was found heterozygous in all members studied. A <jats:italic>PROS1<\/jats:italic> mutation, c.946C\u2009&gt;\u2009T (p.R316C), previously reported to relate to ischemic stroke, was found heterozygous in the patient, his father, and his daughter. Only the proband and daughter have a slightly decreased plasma protein S level. This may be the first case with type 3 VWD with severe VWF\/FVIII deficiency presented with ischemic stroke contributed to by a protein S defect.<\/jats:p>","DOI":"10.1002\/ccr3.6269","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T09:09:52Z","timestamp":1661332192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protein S gene mutation c.<scp>946C<\/scp>\u00a0&gt;\u2009T (p.<scp>R316C<\/scp>) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel <scp>VWF<\/scp> gene mutations, c.<scp>2328delT<\/scp> (p.<scp>A778Lfs<\/scp>* 23) and c.<scp>6521G<\/scp>\u00a0&gt;\u2009T (p.<scp>C2174F<\/scp>)"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1712-0768","authenticated-orcid":false,"given":"Baolai","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Hematology Beijing Shijitan Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Hematology Yuebei People's Hospital affiliated to Medical College of Shantou University  Shaoguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Hematology Clinical Medical College, Yangzhou University  Yangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianjun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Hematology Clinical Medical College, Yangzhou University  Yangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7012-2420","authenticated-orcid":false,"given":"Man\u2010Chiu","family":"Poon","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Calgary, Cumming School of Medicine, Foothills Medical Center, and Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program  Calgary Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-05-782029"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1601561"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2001.3237"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.586289"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12194"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02061.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03975.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12503"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-05-0375"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13175"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.168765"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781444329926.ch3"},{"key":"e_1_2_10_14_1","unstructured":"vWFdb. (2021).International society on thrombosis and Haemostasis scientific and standardization committee VWF information homepage. Available from:www.vwf.group.shef.ac.uk. Accessed 10 December."},{"key":"e_1_2_10_15_1","unstructured":"GeneTests Web site. (2021). Available from:http:\/\/www.ncbi.nlm.nih.gov\/gtr\/. Accessed 10 December."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1646373"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(94)00138-4"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.012877"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00877-1"}],"container-title":["Clinical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.6269","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ccr3.6269","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.6269","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T01:52:07Z","timestamp":1692669127000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ccr3.6269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":18,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/ccr3.6269"],"URL":"https:\/\/doi.org\/10.1002\/ccr3.6269","archive":["Portico"],"relation":{},"ISSN":["2050-0904","2050-0904"],"issn-type":[{"type":"print","value":"2050-0904"},{"type":"electronic","value":"2050-0904"}],"subject":[],"published":{"date-parts":[[2022,8]]},"assertion":[{"value":"2021-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e6269"}}