{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:32:08Z","timestamp":1794047528690,"version":"4.8.0"},"reference-count":82,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"1","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>The gene for von Willebrand factor (VWF) was among the earliest genomic discoveries in the mid-1980s. It became feasible to use this new knowledge to better understand the genetic mechanisms responsible for von Willebrand disease (VWD) and to utilize the information to generate molecular genetic diagnostic testing strategies. Following initial studies demonstrating large structural variants in type 3 VWD patients, investigations focused on the genetic basis of the various type 2 forms of VWD, demonstrating that the pathogenic variants were localized to regions of the gene encoding functionally distinct domains of the VWF glycoprotein. These observations have resulted in increasing use of molecular genetic diagnosis as either the primary strategy for diagnosing type 2 forms of VWD or, more often, as confirmatory tests to substantiate the results of prior phenotypic analysis. In the meantime, genetic studies of type 3 were demonstrating that a wide range of pathogenic variants located throughout the VWF coding sequence were responsible for this severe phenotype. These studies also showed that ~15% of pathogenic variants responsible for type 3 were missense substitutions and that in ~25% of families this severe phenotype, classically thought to be recessive in nature, was transmitted as a semi-dominant trait. Finally, the most prevalent form of VWD, type 1\/Low VWF, has proven to be the most challenging for routine molecular genetic testing, with VWF coding sequence variants identified in only ~65% of index cases. This review explores various aspects of molecular genetic testing for VWF, commemorating the 100th anniversary of VWD and the 40th anniversary of VWF cloning.<\/jats:p>","DOI":"10.3324\/haematol.2024.286014","type":"journal-article","created":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T19:56:56Z","timestamp":1767297416000},"page":"44-53","source":"Crossref","is-referenced-by-count":7,"title":["Molecular genetic testing in von Willebrand disease: past, present, and beyond"],"prefix":"10.3324","volume":"111","author":[{"given":"Omid","family":"Seidizadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lillicrap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"83297","doi-asserted-by":"crossref","unstructured":"Ginsburg D, Handin RI, Bonthron DT. Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization. Science. 1985; 228(4706):1401-1406.","DOI":"10.1126\/science.3874428"},{"key":"83298","doi-asserted-by":"crossref","unstructured":"Sadler JE, Shelton-Inloes BB, Sorace JM, Titani K. Cloning of cDNA and genomic DNA for human von Willebrand factor. Cold Spring Harb Symp Quant Biol. 1986; 51(Pt 1):515-523.","DOI":"10.1101\/SQB.1986.051.01.063"},{"key":"83299","doi-asserted-by":"crossref","unstructured":"Lynch DC, Zimmerman TS, Collins CJ. Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method. Cell. 1985; 41(1):49-56.","DOI":"10.1016\/0092-8674(85)90060-1"},{"key":"83300","doi-asserted-by":"crossref","unstructured":"Verweij CL, de Vries CJ, Distel B. Construction of cDNA coding for human von Willebrand factor using antibody probes for colony-screening and mapping of the chromosomal gene. Nucleic Acids Res. 1985; 13(13):4699-4717.","DOI":"10.1093\/nar\/13.13.4699"},{"key":"83301","doi-asserted-by":"crossref","unstructured":"Vlot AJ, Koppelman SJ, van den Berg MH, Bouma BN, Sixma JJ. The affinity and stoichiometry of binding of human factor VIII to von Willebrand factor. Blood. 1995; 85(11):3150-3157.","DOI":"10.1182\/blood.V85.11.3150.bloodjournal85113150"},{"key":"83302","doi-asserted-by":"crossref","unstructured":"Zimmerman TS, Ratnoff OD, Powell AE. Immunologic differentiation of classic hemophilia (factor 8 deficiency) and von Willebrand\u2019s dissase, with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against antihemophilic factor. J Clin Invest. 1971; 50(1):244-254.","DOI":"10.1172\/JCI106480"},{"key":"83303","doi-asserted-by":"crossref","unstructured":"Sanger F. The Croonian Lecture, 1975. Nucleotide sequences in DNA. Proc R Soc Lond B Biol Sci. 1975; 191:317-333.","DOI":"10.1098\/rspb.1975.0131"},{"key":"83304","doi-asserted-by":"crossref","unstructured":"Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975; 94(3):441-448.","DOI":"10.1016\/0022-2836(75)90213-2"},{"key":"83305","doi-asserted-by":"crossref","unstructured":"Bloom AL. Benefits of cloning genes for clotting factors. Nature. 1983; 303(5917):474-475.","DOI":"10.1038\/303474a0"},{"key":"83306","doi-asserted-by":"crossref","unstructured":"Mancuso DJ, Tuley EA, Westfield LA. Structure of the gene for human von Willebrand factor. J Biol Chem. 1989; 264(33):19514-19527.","DOI":"10.1016\/S0021-9258(19)47144-5"},{"key":"83307","doi-asserted-by":"crossref","unstructured":"Mancuso DJ, Tuley EA, Westfield LA. Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction. Biochemistry. 1991; 30(1):253-269.","DOI":"10.1021\/bi00215a036"},{"key":"83308","doi-asserted-by":"crossref","unstructured":"Lenting PJ, Christophe OD, Denis CV. von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends. Blood. 2015; 125(13):2019-2028.","DOI":"10.1182\/blood-2014-06-528406"},{"key":"83309","doi-asserted-by":"crossref","unstructured":"Zhou YF, Eng ET, Zhu J, Lu C, Walz T, Springer TA. Sequence and structure relationships within von Willebrand factor. Blood. 2012; 120(2):449-458.","DOI":"10.1182\/blood-2012-01-405134"},{"key":"83310","doi-asserted-by":"crossref","unstructured":"Eikenboom JC, Vink T, Bri\u00ebt E, Sixma JJ, Reitsma PH. Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence. Proc Natl Acad Sci U S A. 1994; 91(6):2221-2224.","DOI":"10.1073\/pnas.91.6.2221"},{"key":"83311","doi-asserted-by":"crossref","unstructured":"Seidizadeh O, Baronciani L, Peyvandi F. 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INSERM Network on Molecular Abnormalities in von Willebrand Disease. Thromb Haemost. 1997; 78(1):451-456.","DOI":"10.1055\/s-0038-1657568"},{"key":"83322","doi-asserted-by":"crossref","unstructured":"Lyons SE, Bruck ME, Bowie EJ, Ginsburg D. Impaired intracellular transport produced by a subset of type IIA von Willebrand disease mutations. J Biol Chem. 1992; 267(7):4424-4430.","DOI":"10.1016\/S0021-9258(18)42852-9"},{"key":"83323","doi-asserted-by":"crossref","unstructured":"Hilbert L, Jorieux S, Fontenay-Roupie M. Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene. Br J Haematol. 2004; 127(2):184-189.","DOI":"10.1111\/j.1365-2141.2004.05187.x"},{"key":"83324","doi-asserted-by":"crossref","unstructured":"Lillicrap D, Murray EW, Benford K. Recurring mutations at CpG dinucleotides in the region of the von Willebrand factor gene encoding the glycoprotein Ib binding domain, in patients with type IIB von Willebrand\u2019s disease. Br J Haematol. 1991; 79(4):612-617.","DOI":"10.1111\/j.1365-2141.1991.tb08089.x"},{"key":"83325","doi-asserted-by":"crossref","unstructured":"Mancuso DJ, Kroner PA, Christopherson PA, Vokac EA, Gill JC, Montgomery RR. Type 2M:Milwaukee-1 von Willebrand disease: an in-frame deletion in the Cys509-Cys695 loop of the von Willebrand factor A1 domain causes deficient binding of von Willebrand factor to platelets. Blood. 1996; 88(7):2559-2568.","DOI":"10.1182\/blood.V88.7.2559.bloodjournal8872559"},{"key":"83326","doi-asserted-by":"crossref","unstructured":"Flood VH, Schlauderaff AC, Haberichter SL. Crucial role for the VWF A1 domain in binding to type IV collagen. Blood. 2015; 125(14):2297-2304.","DOI":"10.1182\/blood-2014-11-610824"},{"key":"83327","doi-asserted-by":"crossref","unstructured":"Doruelo AL, Haberichter SL, Christopherson PA. Clinical and laboratory phenotype variability in type 2M von Willebrand disease. J Thromb Haemost. 2017; 15(8):1559-1566.","DOI":"10.1111\/jth.13742"},{"key":"83328","doi-asserted-by":"crossref","unstructured":"Sadler JE, Budde U, Eikenboom JC. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost. 2006; 4(10):2103-2114.","DOI":"10.1111\/j.1538-7836.2006.02146.x"},{"key":"83329","doi-asserted-by":"crossref","unstructured":"Goodeve A, Eikenboom J, Castaman G. Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) [published correction appears in Blood. Blood. 2008; 111(6):3299-300.","DOI":"10.1182\/blood-2007-11-123695"},{"key":"83330","doi-asserted-by":"crossref","unstructured":"James PD, Notley C, Hegadorn C. The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study. Blood. 2007; 109(1):145-154.","DOI":"10.1182\/blood-2006-05-021105."},{"key":"83331","doi-asserted-by":"crossref","unstructured":"Flood VH, Christopherson PA, Gill JC. Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States. Blood. 2016; 127(20):2481-2488.","DOI":"10.1182\/blood-2015-10-673681"},{"key":"83332","doi-asserted-by":"crossref","unstructured":"Cumming A, Grundy P, Keeney S. An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease. Thromb Haemost. 2006; 96(5):630-641.","DOI":"10.1160\/TH06-07-0383"},{"key":"83333","doi-asserted-by":"crossref","unstructured":"Rydz N, James PD. The evolution and value of bleeding assessment tools. J Thromb Haemost. 2012; 10(11):2223-2229.","DOI":"10.1111\/j.1538-7836.2012.04923.x"},{"key":"83334","doi-asserted-by":"crossref","unstructured":"Tosetto A, Castaman G, Rodeghiero F. Assessing bleeding in von Willebrand disease with bleeding score. Blood Rev. 2007; 21(2):89-97.","DOI":"10.1016\/j.blre.2006.04.002"},{"key":"83335","doi-asserted-by":"crossref","unstructured":"Federici AB. Clinical and laboratory diagnosis of VWD. Hematology Am Soc Hematol Educ Program. 2014; 2014(1):524-530.","DOI":"10.1182\/asheducation-2014.1.524"},{"key":"83336","doi-asserted-by":"crossref","unstructured":"Bowman ML, James PD. Bleeding scores for the diagnosis of von Willebrand disease. Semin Thromb Hemost. 2017; 43(5):530-539.","DOI":"10.1055\/s-0036-1597289"},{"key":"83337","doi-asserted-by":"crossref","unstructured":"Leebeek FW, Eikenboom JC. von Willebrand\u2019s disease. N Engl J Med. 2016; 375(21):2067-2080.","DOI":"10.1056\/NEJMra1601561"},{"key":"83338","doi-asserted-by":"crossref","unstructured":"James PD, Connell NT, Ameer B. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv. 2021; 5(1):280-300.","DOI":"10.1182\/bloodadvances.2020003265"},{"key":"83339","doi-asserted-by":"crossref","unstructured":"Seidizadeh O, Eikenboom JCJ, Denis CV. von Willebrand disease. Nat Rev Dis Primers. 2024; 10(1):51.","DOI":"10.1038\/s41572-024-00536-8"},{"key":"83340","doi-asserted-by":"crossref","unstructured":"Favaloro EJ. Navigating the myriad of von Willebrand factor assays. Hamostaseologie. 2020; 40(4):431-442.","DOI":"10.1055\/s-0040-1713735"},{"key":"83341","doi-asserted-by":"crossref","unstructured":"Seidizadeh O, Baronciani L, Lillicrap D, Peyvandi F. Application of genetic testing for the diagnosis of von Willebrand disease. J Thromb Haemost. 2024; 22(8):2115-2128.","DOI":"10.1016\/j.jtha.2024.05.006"},{"key":"83342","doi-asserted-by":"crossref","unstructured":"Seidizadeh O, Mollica L, Zambarbieri S. Type 2M\/2A von Willebrand disease: a shared phenotype between type 2M and 2A. Blood Adv. 2024; 8(7):1725-1736.","DOI":"10.1182\/bloodadvances.2024012626"},{"key":"83343","doi-asserted-by":"crossref","unstructured":"Veyradier A, Boisseau P, Fressinaud E. A laboratory phenotype\/genotype correlation of 1167 French patients from 670 families with von Willebrand disease: a new epidemiologic picture. Medicine (Baltimore). 2016; 95(11):e3038.","DOI":"10.1097\/MD.0000000000003038"},{"key":"83344","doi-asserted-by":"crossref","unstructured":"Seidizadeh O, Baronciani L, Pagliari MT. Phenotypic and genetic characterizations of the Milan cohort of von Willebrand disease type 2. Blood Adv. 2022; 6(13):4031-4040.","DOI":"10.1182\/bloodadvances.2022007216"},{"key":"83345","doi-asserted-by":"crossref","unstructured":"Ramanan R, Van Laer C, Baert S. Clinical utility of panelbased genetic sequencing for von Willebrand disease. Res Pract Thromb Haemost. 2025; 9(2):102730.","DOI":"10.1016\/j.rpth.2025.102730"},{"key":"83346","doi-asserted-by":"crossref","unstructured":"Goodeve AC. The genetic basis of von Willebrand disease. Blood Rev. 2010; 24(3):123-134.","DOI":"10.1016\/j.blre.2010.03.003"},{"key":"83347","doi-asserted-by":"crossref","unstructured":"Daniel MY, Ternisien C, Castet S. Type 2N von Willebrand disease: genotype drives different bleeding phenotypes and treatment needs. J Thromb Haemost. 2024; 22(10):2702-2712.","DOI":"10.1016\/j.jtha.2024.06.020"},{"key":"83348","doi-asserted-by":"crossref","unstructured":"Seidizadeh O, Peyvandi F, Mannucci PM. Von Willebrand disease type 2N: an update. J Thromb Haemost. 2021; 19(4):909-916.","DOI":"10.1111\/jth.15247"},{"key":"83349","doi-asserted-by":"crossref","unstructured":"Othman M, Lillicrap D. Distinguishing between non-identical twins: platelet type and type 2B von Willebrand disease. Br J Haematol. 2007; 138(5):665-666.","DOI":"10.1111\/j.1365-2141.2007.06690.x"},{"key":"83350","doi-asserted-by":"crossref","unstructured":"Fu A, Kazmirchuk TDD, Bradbury-Jost C, Golshani A, Othman M. Platelet-type von Willebrand disease: complex pathophysiology and insights on novel therapeutic and diagnostic strategies. Semin Thromb Hemost. 2025; 51(2):219-226.","DOI":"10.1055\/s-0044-1789183"},{"key":"83351","doi-asserted-by":"crossref","unstructured":"Borr\u00e0s N, Batlle J, P\u00e9rez-Rodr\u00edguez A. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVWES): comprehensive genetic analysis by next-generation sequencing of 480 patients. Haematologica. 2017; 102(12):2005-2014.","DOI":"10.3324\/haematol.2017.168765"},{"key":"83352","doi-asserted-by":"crossref","unstructured":"Lapi\u0107 I, Radi\u0107 Antolic M, Boban A, Coen Herak D, Rogi\u0107 D, Zadro R. Next-generation sequencing of von Willebrand factor and coagulation factor VIII genes: a cross-sectional study in Croatian adult patients diagnosed with von Willebrand disease. Croat Med J. 2022; 63(2):166-175.","DOI":"10.3325\/cmj.2022.63.166"},{"key":"83353","doi-asserted-by":"crossref","unstructured":"Zhang B, Spreafico M, Zheng C. Genotype-phenotype correlation in combined deficiency of factor V and factor VIII. Blood. 2008; 111(12):5592-5600.","DOI":"10.1182\/blood-2007-10-113951"},{"key":"83354","doi-asserted-by":"crossref","unstructured":"Bowman M, Tuttle A, Notley C. The genetics of Canadian type 3 von Willebrand disease: further evidence for co-dominant inheritance of mutant alleles. J Thromb Haemost. 2013; 11(3):512-520.","DOI":"10.1111\/jth.12130"},{"key":"83355","doi-asserted-by":"crossref","unstructured":"Baronciani L, Peake I, Schneppenheim R. Genotypes of European and Iranian patients with type 3 von Willebrand disease enrolled in 3WINTERS-IPS. Blood Adv. 2021; 5(15):2987-3001.","DOI":"10.1182\/bloodadvances.2020003397"},{"key":"83356","doi-asserted-by":"crossref","unstructured":"Christopherson PA, Haberichter SL, Flood VH. Molecular pathogenesis and heterogeneity in type 3 VWD families in U.S. Zimmerman program. J Thromb Haemost. 2022; 20(7):1576-1588.","DOI":"10.1111\/jth.15713"},{"key":"83357","doi-asserted-by":"crossref","unstructured":"Peake IR, Goodeve AC. Genetic testing for von Willebrand disease: the case for. J Thromb Haemost. 2010; 8(1):13-16.","DOI":"10.1111\/j.1538-7836.2009.03670.x"},{"key":"83358","doi-asserted-by":"crossref","unstructured":"Favaloro EJ. Genetic testing for von Willebrand disease: the case against. J Thromb Haemost. 2010; 8(1):6-12.","DOI":"10.1111\/j.1538-7836.2009.03482.x"},{"key":"83359","doi-asserted-by":"crossref","unstructured":"Casonato A, Pontara E, Sartorello F. Reduced von Willebrand factor survival in type Vicenza von Willebrand disease. Blood. 2002; 99(1):180-184.","DOI":"10.1182\/blood.V99.1.180"},{"key":"83360","doi-asserted-by":"crossref","unstructured":"Connell NT, Flood VH, Brignardello-Petersen R. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv. 2021; 5(1):301-325.","DOI":"10.1182\/bloodadvances.2020003264"},{"key":"83361","doi-asserted-by":"crossref","unstructured":"Eikenboom J, Federici AB, Dirven RJ. VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease. Blood. 2013; 121(12):2336-2339.","DOI":"10.1182\/blood-2012-09-455089"},{"key":"83362","doi-asserted-by":"crossref","unstructured":"Seidizadeh O, Baronciani L, Pagliari MT. 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