Update of von Willebrand Factor Gene Defects from the ISTH VWF Web Site Update of von Willebrand Factor Gene Defects from the ISTH VWF Web Site Anne Goodeve.

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Update of von Willebrand Factor Gene Defects from the ISTH VWF Web Site Update of von Willebrand Factor Gene Defects from the ISTH VWF Web Site Anne Goodeve and Nick Beauchamp University of Sheffield, UK Ross MacLachlan and David Lillicrap Kingston, Canada

VWD Type in 307 Entries 2A 2B 1 U 3 2N2M

Type 1 VWD, n=14 2 small deletions (frameshift) 1 nonsense mutation 11 missense mutations; –Ex 26, 28 and 52 –Codons –C1130F; n=1 –C1149R; n=1 –T1156M; n=2 –Y1584C; n=1

Type 2A VWD, n=71 SubtypeExonDomainCodonsNo. reports IIC12-16D D’771fs1 28A A IID52CK2773fs1 IIE52CK Total71

Common Type 2A VWD Mutations Amino acid changeNo. reports% of 71 type 2A S1506L811 R1597Q46 R1597W913 G1609R34 Total2434

Type 2B VWD, n=52 Exon 28 Codons A1 domain 1 insertion mutation (1304insM) 16 different missense mutations at 10 amino acids

Common Type 2B VWD Mutations Amino acid changeNo. reports% of 52 type 2B R1306W1019 R1308C612 V1316M917 R1341Q713 Total3261

Type 2M; n=18 Ex 18, 27 and 28 (n=16) D’, D3 and A1 domains Codons 788, 1205 and No common mutations reported I1425F reported twice

Type 2N; n=37 Ex18-24 Codons D’ and D3 domains 16 different missense changes at 15 amino acids (R816W, R816Q)

Common Type 2N VWD Mutations Amino acid changeNo. reports% of 37 type 2N T791M514 R816W411 R854Q1232 Total2157

Type 3 VWD, n=85 Mutations throughout VWF

Type 3 VWD Mutation Type Nonsense Missense SpliceSmall deletion Large deletion Insertion R1659X, n=5 R2535X, n=4 D141N D141Y 5/6 into C or T run 42, 23-52, all VWF x3 2435delC x6 dinucleotide from repeat x3 all unique

“Unclassified” VWD 30 entries 1 large deletion Ex deletion 3 nt (2 aa substitution) 1 insertion 105 nt (sequence duplication) 27 missense

“Unclassified” VWD, n=30 ExonDomainAmino acid change No. reports Phenotype 25-26D Q Bern in 1 27D3R1205H/L2Vicenza 28A1R1374C/H/L/S5 30A1S1371T1Decreased collagen binding 38D4L2207P1 52CKC2806R1Dimer defect

VWF Mutation Type in 307 Entries Missense Insertion Nonsense Small del SpliceLarge del

S D1 D2 D’ D3 A1 A2 A3 D4 B1-B3 C1 C2 CK Location of 307 VWF Mutations D’-D3 21 A 54 D4-CK 11 D1-D2 12 % of 307 mutations Large deletions 2%

Send suggestions/comments/mutations/polymorphisms to the database manager Complete form at this meeting, pass to Anne Goodeve/ post / Fax to Sheffield

AcknowledgementsAcknowledgements Aventis David Lillicrap Ross MacLachlan Nick Beauchamp - database manager