{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:33:13Z","timestamp":1780047193514,"version":"3.53.1"},"reference-count":33,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The 3\u2032 end of the VWF gene was screened in the affected members of 3 different families with type 2A (phenotype IID) von Willebrand disease (vWD). Exons 49 to 52 of the VWF gene were amplified and screened for mutations by chemical cleavage mismatch detection. Mismatched bands were detected in exon 52 of 2 patients and in exon 51 of a third patient. Using direct DNA sequencing, a heterozygous G8562A transition leading to a Cys2008Tyr substitution was found in all the patients in family 1, and a T8561A transversion leading to a Cys2008Ser substitution was found in both patients from family 2. In a patient from a third family, an 8-base deletion from nucleotide 8437 to 8444 was identified in exon 51. The 2 mutations in exon 52 were reproduced by in vitro site-directed mutagenesis of full-length von Willebrand factor (vWF) cDNA and transiently expressed in COS-7 cells. The corresponding recombinant VWFs for these 2 mutations exhibited the typical aberrant vWF:Ag multimer pattern seen in the plasma of the patients. These 3 mutations demonstrate the importance of other carboxy-terminal cysteines in addition to the reported Cys2010 residue, in the normal dimerization of vWF, and their essential role in the assembly of normal multimeric vWF.<\/jats:p>","DOI":"10.1182\/blood.v98.3.674","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"674-680","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":30,"title":["Aberrant dimerization of von Willebrand factor as the result of mutations in the carboxy-terminal region: identification of 3 mutations in members of 3 different families with type 2A (phenotype IID) von Willebrand disease"],"prefix":"10.1182","volume":"98","author":[{"given":"M. Said","family":"Enayat","sequence":"first","affiliation":[{"name":"From the Molecular Haemostasis Laboratory, Department of Haematology, The Birmingham Children's Hospital NHS Trust; the Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free and University College Medical School, London; the Division of Haematology, University of Leicester; and the Department of Haematology, The Royal Liverpool University Hospitals, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Guilliatt","sequence":"additional","affiliation":[{"name":"From the Molecular Haemostasis Laboratory, Department of Haematology, The Birmingham Children's Hospital NHS Trust; the Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free and University College Medical School, London; the Division of Haematology, University of Leicester; and the Department of Haematology, The Royal Liverpool University Hospitals, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurcharan K.","family":"Surdhar","sequence":"additional","affiliation":[{"name":"From the Molecular Haemostasis Laboratory, Department of Haematology, The Birmingham Children's Hospital NHS Trust; the Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free and University College Medical School, London; the Division of Haematology, University of Leicester; and the Department of Haematology, The Royal Liverpool University Hospitals, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Vincent","family":"Jenkins","sequence":"additional","affiliation":[{"name":"From the Molecular Haemostasis Laboratory, Department of Haematology, The Birmingham Children's Hospital NHS Trust; the Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free and University College Medical School, London; the Division of Haematology, University of Leicester; and the Department of Haematology, The Royal Liverpool University Hospitals, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. John","family":"Pasi","sequence":"additional","affiliation":[{"name":"From the Molecular Haemostasis Laboratory, Department of Haematology, The Birmingham Children's Hospital NHS Trust; the Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free and University College Medical School, London; the Division of Haematology, University of Leicester; and the Department of Haematology, The Royal Liverpool University Hospitals, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Hock","family":"Toh","sequence":"additional","affiliation":[{"name":"From the Molecular Haemostasis Laboratory, Department of Haematology, The Birmingham Children's Hospital NHS Trust; the Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free and University College Medical School, London; the Division of Haematology, University of Leicester; and the Department of Haematology, The Royal Liverpool University Hospitals, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Williams","sequence":"additional","affiliation":[{"name":"From the Molecular Haemostasis Laboratory, Department of Haematology, The Birmingham Children's Hospital NHS Trust; the Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free and University College Medical School, London; the Division of Haematology, University of Leicester; and the Department of Haematology, The Royal Liverpool University Hospitals, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G. H.","family":"Hill","sequence":"additional","affiliation":[{"name":"From the Molecular Haemostasis Laboratory, Department of Haematology, The Birmingham Children's Hospital NHS Trust; the Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free and University College Medical School, London; the Division of Haematology, University of Leicester; and the Department of Haematology, The Royal Liverpool University Hospitals, Liverpool, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021221114877900_B1","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1172\/JCI107470","article-title":"Culture of human endothelial cells derived from umbilical veins: identification by morphological and immunological criteria.","volume":"52","author":"Jaffe","year":"1973","journal-title":"J Clin Invest."},{"key":"2020021221114877900_B2","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1172\/JCI108846","article-title":"Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes.","volume":"60","author":"Nachman","year":"1977","journal-title":"J Clin Invest."},{"key":"2020021221114877900_B3","doi-asserted-by":"crossref","first-page":"15679","DOI":"10.1016\/S0021-9258(18)66771-7","article-title":"Substructure of human von Willebrand factor.","volume":"261","author":"Fretto","year":"1986","journal-title":"J Biol Chem."},{"key":"2020021221114877900_B4","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1083\/jcb.99.6.2123","article-title":"Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization.","volume":"99","author":"Wagner","year":"1984","journal-title":"J Cell Biol."},{"key":"2020021221114877900_B5","doi-asserted-by":"crossref","first-page":"8099","DOI":"10.1021\/bi00399a013","article-title":"Identification of disulfide-bridged substructures within human von Willebrand factor.","volume":"26","author":"Marti","year":"1987","journal-title":"Biochemistry."},{"key":"2020021221114877900_B6","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1182\/blood.V57.6.1140.1140","article-title":"The complex multimeric composition of factor VIII\/von Willebrand factor.","volume":"57","author":"Ruggeri","year":"1981","journal-title":"Blood."},{"key":"2020021221114877900_B7","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1042\/bj3310483","article-title":"Triplet structure of human von Willebrand factor.","volume":"331","author":"Fischer","year":"1998","journal-title":"Biochem J."},{"key":"2020021221114877900_B8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1055\/s-0038-1642670","article-title":"Molecular mechanism and classification of von Willebrand disease.","volume":"74","author":"Sadler","year":"1995","journal-title":"Thromb Haemost."},{"key":"2020021221114877900_B9","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1182\/blood.V70.3.605.605","article-title":"Review: structure-function relationship of human von Willebrand Factor.","volume":"70","author":"Girma","year":"1987","journal-title":"Blood."},{"key":"2020021221114877900_B10","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1055\/s-0038-1657568","article-title":"and the INSERM Network on Molecular Abnormalities in von Willebrand disease. 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