A New (K1518E) Candidate Mutation Detected by Universal Heteroduplex Generator Analysis in a Patient with Type 2A (Phenotype IIA) von Willebrand Disease

1998 ◽  
Vol 79 (01) ◽  
pp. 240-240 ◽  
Author(s):  
Bimal Theophilus ◽  
Frank Hill ◽  
Peter Rose ◽  
Doris Culpan ◽  
Jeffery Bidwell ◽  
...  
Keyword(s):  
Von Willebrand Disease ◽  
Candidate Mutation ◽  
Von Willebrand

scholarly journals Identification of a new candidate mutation, G1629R, in a family with type 2A von Willebrand disease

1999 ◽  
Vol 60 (4) ◽  
pp. 309-310 ◽  
Author(s):  
Pilar Casa�a ◽  
Francisco Mart�nez ◽  
Saturnino Haya ◽  
Jos� A. Aznar
Keyword(s):  
Von Willebrand Disease ◽  
Candidate Mutation ◽  
Von Willebrand

scholarly journals A Patient With Type 2N von Willebrand Disease Is Heterozygous for a New Mutation: Gly22Glu. Demonstration of a Defective Expression of the Second Allele by the Use of Monoclonal Antibodies

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3263-3269 ◽  
Author(s):  
J. Gu ◽  
S. Jorieux ◽  
J.M. Lavergne ◽  
C. Ruan ◽  
C. Mazurier ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chinese Patient ◽  
Von Willebrand Disease ◽  
Expression Vectors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Binding Ability ◽  
New Mutation ◽  
Candidate Mutation ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractWe report the case of a Chinese patient who has subnormal von Willebrand factor (vWF ) level and normal vWF multimeric pattern, but a lack of vWF capacity to bind factor VIII (FVIII). Exons 18 to 20 of the patient's vWF gene were analyzed by DGGE and a G2354 → A substitution which changes the encoded amino acid sequence from Gly22 to Glu was identified. The patient is heterozygous for this substitution, creating a unique Sac I restriction site. Recombinant vWF (rvWF ) containing the candidate mutation was transiently expressed in COS-7 cells. It was processed and secreted normally but failed to bind FVIII. FVIII binding ability of hybrid rvWF, obtained by cotransfection of normal and mutated expression vectors and corresponding to a heterozygous genotype, was moderately decreased. To explain this functional discrepancy between patient's plasma vWF and hybrid rvWF, we used anti-vWF monoclonal antibodies (MoAbs) as capture in an enzyme-linked immunosorbent assay test. MoAb 32B12 recognized both wild-type and mutated rvWFs whereas MoAb 418 did not recognize mutated rvWF. Because MoAb 418 also failed to capture the plasma vWF from propositus, it means that his second nonmutated allele is not expressed or expressed at a very low level.

Von Willebrand Disease Type 2M “Vicenza” in Italian and German Patients: Identification of the First Candidate Mutation (G3864A; R1205H) in 8 Families

2000 ◽  
Vol 83 (01) ◽  
pp. 136-140 ◽  
Author(s):  
Augusto Federici ◽  
Ulrich Budde ◽  
Giancarlo Castaman ◽  
Elke Drewke ◽  
Sonja Krey ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Mutation Screening ◽  
Normal Subjects ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Heteroduplex Analysis ◽  
Molecular Defect ◽  
Coding Region ◽  
Candidate Mutation ◽  
Von Willebrand

SummaryVon Willebrand disease type 2M “Vicenza” (VWD 2M V) is characterised by autosomal dominant inheritance, low von Willebrand factor (VWF) and the presence of “supranormal” multimers in plasma. This specific phenotype has been described in Italian and recently also in German patients. The molecular defect is linked to the VWF gene. However, no specific mutations have been identified until now. We analysed the complete coding region and adjacent intron sequences of the VWF gene in Italian families in comparison to German families with VWD 2M V by a PCR-based mutation screening, combined with SSC-and heteroduplex-analysis of exons 2 through 52, followed by direct sequencing. We identified the first heterozygous candidate mutation (G3864A; R1205H) in all affected members of the 7 Italian families and in 1 German patient but not in the unaffected family members nor on 100 chromosomes of normal subjects, suggesting a causal relationship between the mutation and the phenotype. Haplotype identity, with minor deviations in one Italian family, suggests a common but not very recent genetic origin of R1205H.

scholarly journals Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2433-2441 ◽  
Author(s):  
JC Eikenboom ◽  
T Matsushita ◽  
PH Reitsma ◽  
EA Tuley ◽  
G Castaman ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Direct Sequencing ◽  
Von Willebrand Disease ◽  
Cysteine Residues ◽  
Dominant Type ◽  
Dominant Phenotype ◽  
Candidate Mutation ◽  
Von Willebrand ◽  
Willebrand Factor

No defects have been reported in moderately severe type 1 von Willebrand disease (vWD) with a clear autosomal dominant inheritance pattern, and the mechanism underlying this form of vWD remains obscure. We have studied a type 1 vWD family with such a dominant phenotype. The entire coding sequence of the von Willebrand factor (vWF) gene was analyzed by direct sequencing of DNA fragments amplified by polymerase chain reaction. Only one candidate mutation T(3445)-->C in exon 26 was detected that predicts a replacement of cysteine (C) at position 386 of the mature vWF subunit by arginine (R). Both mutant and normal vWF alleles were expressed as shown by analysis of platelet mRNA. This substitution segregates with vWD in the family and was not found in 100 unrelated individuals. The recombinant mutant vWF(C386R) was characterized by expression in 293T cells. The secretion of vWF(C386R) was greatly impaired due to retention in the endoplasmic reticulum. In cotransfections of normal and mutant vWF constructs, the vWF(C386R) subunits caused a dose-dependent decrease in the secretion of vWF. The multimer pattern remained nearly normal and consistent with a dominant vWD type 1 phenotype. The importance of the cysteine residues in the D3 domain of vWF in the pathogenesis of dominant type 1 vWD was further shown by the detection of another cysteine mutation, Cys367-->Phe, in two additional unrelated patients with a similar dominant type 1 vWD phenotype. We conclude that the loss of cysteine pairing in the D3 domain, leaving one free cysteine, can induce a purely quantitative deficiency of vWF by dominantly suppressing the secretion of normal vWF.

Morbidity and mortality of patients with haemophilia in Germany 2007/2008

2009 ◽  
Vol 29 (S 01) ◽  
pp. S7-S12
Author(s):  
M. Spannagl ◽  
W. Schramm ◽  
H. Krebs ◽  
Keyword(s):  
Causes Of Death ◽  
Severity Of Illness ◽  
Von Willebrand Disease ◽  
Morbidity And Mortality ◽  
Haemophilia A ◽  
Hiv Status ◽  
Von Willebrand ◽  
Existing Data

SummarySince 1978 an annual multicentric survey regarding the epidemiology of patients suffering of haemophilia is performed with support of haemophilia treating centres of any size. Again the actual compilation is resting upon a broad database returning to over 30 years of inquiry well representing both the actual and retrospective status of mortality. Prompted was exclusively information about patients with haemophilia A, B and von Willebrand disease. In particular anonymous data concerning the last 12 months about number of treated patients, type and severity of illness, HIV-status and detailed information about causes of death was inquired. This data was merged with existing data and analyzed statistically. In the 2007/2008 survey, a total

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