{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:10:33Z","timestamp":1791141033025,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,18]],"date-time":"2013-03-18T00:00:00Z","timestamp":1363564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2013,7]]},"abstract":"Summary<\/jats:title>Type 2M von Willebrand disease (VWD<\/jats:styled-content>) includes qualitative defects in von W<\/jats:styled-content>illebrand factor (VWF<\/jats:styled-content>) function, with normal multimer distribution but a defect in VWF<\/jats:styled-content> activity with respect to platelet or collagen binding. We characterized novel VWF<\/jats:italic><\/jats:styled-content> gene mutations found in type 2M VWD<\/jats:styled-content> subjects enrolled in the Zimmerman Program for the Molecular and Clinical Biology of VWD<\/jats:styled-content>. Subjects were enrolled based on a pre\u2010existing diagnosis of type 2M VWD<\/jats:styled-content>. Testing included full\u2010length gene sequencing, VWF<\/jats:styled-content> antigen (VWF<\/jats:styled-content>:Ag), VWF<\/jats:styled-content> ristocetin cofactor activity (VWF<\/jats:styled-content>:RCo<\/jats:styled-content>), VWF<\/jats:styled-content> collagen binding and multimer distribution. Recombinant VWF<\/jats:styled-content> variants were synthesized using site\u2010directed mutagenesis and expressed in HEK293T<\/jats:styled-content> cells. Platelet binding was measured by flow cytometry with fixed platelets and ELISA with recombinant glycoprotein Ib\u03b1 (GPIb\u03b1<\/jats:styled-content>). Four novel VWF<\/jats:styled-content> A1 domain mutations were found in individuals with type 2M VWD<\/jats:styled-content>: S1358N, S1387I, S1394F and Q1402P. All subjects had a history of bleeding, VWF<\/jats:styled-content>:RCo<\/jats:styled-content>\u00a0<\u00a040\u00a0IU\u00a0dL\u22121<\/jats:sup>, VWF<\/jats:styled-content>:RCo<\/jats:styled-content>\/VWF<\/jats:styled-content>:Ag<\/jats:styled-content> ratios <0.6 and normal multimer distribution. No defect in expression, secretion, or multimerization was found for any of the mutations. All showed decreased binding to intact platelets, and decreased or absent binding to a mutant GPIb\u03b1<\/jats:styled-content> construct with spontaneous VWF<\/jats:styled-content> binding. 1387I had decreased binding to all collagen types tested. 1402P had reduced binding exclusively to type VI collagen. Type 2M VWD<\/jats:styled-content> is a heterogeneous category comprised of both collagen\u2010 and platelet\u2010binding defects. Understanding the precise defect for each mutation may ultimately lead to better diagnosis and treatment.<\/jats:p>","DOI":"10.1111\/hae.12117","type":"journal-article","created":{"date-parts":[[2013,3,18]],"date-time":"2013-03-18T08:45:03Z","timestamp":1363596303000},"page":"590-594","source":"Crossref","is-referenced-by-count":27,"title":["Variability in platelet\u2010 and collagen\u2010binding defects in type 2M von Willebrand disease"],"prefix":"10.1111","volume":"19","author":[{"given":"D. M.","family":"Larsen","sequence":"first","affiliation":[{"name":"Medical College of Wisconsin Milwaukee WI USA"},{"name":"Children's Research Institute Children's Hospital of Wisconsin Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. L.","family":"Haberichter","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin Milwaukee WI USA"},{"name":"Children's Research Institute Children's Hospital of Wisconsin Milwaukee WI USA"},{"name":"Blood Research Institute Blood Center of Wisconsin Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C.","family":"Gill","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin Milwaukee WI USA"},{"name":"Children's Research Institute Children's Hospital of Wisconsin Milwaukee WI USA"},{"name":"Blood Research Institute Blood Center of Wisconsin Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. D.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Indiana Hemophilia and Thrombosis Center Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. H.","family":"Flood","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin Milwaukee WI USA"},{"name":"Children's Research Institute Children's Hospital of Wisconsin Milwaukee WI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02146.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1657568"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-27820"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1281031"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01643.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1182\/blood.V88.7.2559.bloodjournal8872559","article-title":"Type 2M:Milwaukee\u20101 von Willebrand disease: an in\u2010frame deletion in the Cys509\u2010Cys695 loop of the von Willebrand factor A1 domain causes deficient binding of von Willebrand factor to platelets","volume":"88","author":"Mancuso DJ","year":"1996","journal-title":"Blood"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1182\/blood.V91.5.1572","article-title":"Type 2M von Willebrand disease: F606I and I662F mutations in the glycoprotein ib binding domain selectively impair ristocetin\u2010 but not botrocetin\u2010mediated binding of von Willebrand factor to platelets","volume":"91","author":"Hillery CA","year":"1998","journal-title":"Blood"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0021-9258(17)42483-5","article-title":"von Willebrand factor. 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