Clinical phenotype in genetically confirmed von Willebrand disease type 2N patients reflects a haemophilia A phenotype

Haemophilia ◽  
2015 ◽  
Vol 21 (5) ◽  
pp. e375-e383 ◽  
Author(s):  
M. E. R. van Meegeren ◽  
T. L. Mancini ◽  
S. C. M. Schoormans ◽  
B. J. T. van Haren ◽  
C. van Duren ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Haemophilia A ◽  
Von Willebrand

Results of a Screening for von Willebrand Disease Type 2N in Patients with Suspected Haemophilia A or von Willebrand Disease Type 1

1996 ◽  
Vol 76 (04) ◽  
pp. 598-602 ◽  
Author(s):  
Reinhard Schneppenheim ◽  
Ulrich Budde ◽  
Sonja Krey ◽  
Elke Drewke ◽  
Frauke Bergmann ◽  
...  
Keyword(s):  
Factor Viii ◽  
Screening Program ◽  
Residual Activity ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Compound Heterozygous ◽  
Haemophilia A ◽  
Von Willebrand ◽  
Common Defect

SummaryA screening program for the detection of patients with von Willebrand disease type 2N (VWD 2N) was carried out in 177 unrelated patients previously diagnosed with haemophilia A and in 199 unrelated patients with VWD type 1 in comparison. By measuring the factor VIII (FVIII) binding capacity of von Willebrand factor (VWF), we detected 13 patients with VWD 2N within 8 unrelated families. The former diagnosis has been haemophilia A in 5 index patients, and VWD in the remaining 3. Included in this study were 14 patients with suspected haemophilia A, whose molecular analysis for mutations in the FVIII gene was unsuccessful. Five of them had VWD 2N. In all patients with the VWD 2N phenotype we were able to identify specific molecular defects in the corresponding DNA sequence of the FVIII binding domain of VWF. The most common defect was R91Q. Four patients from 4 families were homozygous for R91Q, six patients from 3 families were compound heterozygous for R91Q and a silent yet unidentified allele. The VWD 2N phenotype of father, daughter, and son in one family, was based on 2 different genotypes, compound heterozygosity for R91Q and VWD type 1 in the father and the daughter, and homozygosity for R91Q in the son. Two patients from one family were compound heterozygous for T28M and ΔC2680-2685 in exon 18, and one patient was compound heterozygous for a novel candidate missense mutation in exon 18 (E24K) and ΔC2680-2685 in exon 18 which is regarded the most common defect causing severe VWD type 3. FVIII:C values of 0.07 and 0.14 IU/ml were observed in patients with the genotype T28MIΔC2680-2685 whereas in patients being homozygous or compound heterozygous for R91Q, FVIII:C was 0.19 ° 0.071 IU/ml. In contrast to the other genotypes, E24KIΔC2680-2685 is correlated with a more severe haemophilic phenotype with a FVIII residual activity of only 0.01-0.02 IU/ml. This emphasizes the need for inclusion of the factor VIII binding assay in the diagnostic workup of suspected haemophilia A.

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

Response to DDAVP in children with von Willebrand disease type 2

2009 ◽  
Vol 29 (02) ◽  
pp. 143-148 ◽  
Author(s):  
U. Budde ◽  
K. Beutel ◽  
W.-A. Hassenpflug ◽  
H. Hauch ◽  
T. Obser ◽  
...  
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Molecular Defect ◽  
Variable Response ◽  
Functional Parameters ◽  
Functional Defect ◽  
Biologic Response ◽  
High Level ◽  
Von Willebrand

SummaryWe have prospectively evaluated the biologic response to desmopressin (DDAVP) in 28 children with type 2 von Willebrand disease (VWD) in correlation with the phenotype and the molecular defect of VWF. The diagnosis of VWD type 2 was mainly based on VWF functional parameters and/or an aberrant VWF multimer pattern. Seventeen different mutations were identified (6 of them novel). No response with respect to the functional parameters VWF:RCo and/or VWF:CB was seen in patients with severe abnormality of the VWF multimer pattern. One patient with VWD type 2A phenotype IIC Miami did not respond with respect to VWF:CB, but showed a good response of VWF:Ag and FVIII:C as expected. Interestingly he showed a persistently high level of VWF:Ag and FVIII:C up to 4 hours after DDAVP infusion. Patients with minor alterations of multimer structure and particular mutations responded well to DDAVP, whereas patients with normal multimer structure but a defect in platelet dependent functional parameters did not respond with VWF:RCo. Conclusion: Children with VWD type 2 show a variable response to desmopressin depending on the mutation that correlates with the functional defect and the presence or absence as well as the half-life of large VWF multimers. Our data emphasize the usefulness of DDAVP testing even in patients with VWD type 2, possibly with the exception of VWD type 2B.

Characterisation of Type 2N von Willebrand Disease Using Phenotypic and Molecular Techniques

1996 ◽  
Vol 75 (06) ◽  
pp. 959-964 ◽  
Author(s):  
I M Nesbitt ◽  
A C Goodeve ◽  
A M Guilliatt ◽  
M Makris ◽  
F E Preston ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Von Willebrand Disease ◽  
Molecular Techniques ◽  
Haemophilia A ◽  
Binding Region ◽  
Gene Encoding ◽  
Covalently Linked ◽  
Von Willebrand ◽  
Willebrand Factor

Summaryvon Willebrand factor (vWF) is a multimeric glycoprotein found in plasma non covalently linked to factor VIII (FVIII). Type 2N von Willebrand disease (vWD) is caused by a mutation in the vWF gene that results in vWF with a normal multimeric pattern, but with reduced binding to FVIII.We have utilised methods for the phenotypic and genotypic detection of type 2N vWD. The binding of FVIII to vWF in 69 patients, 36 with type 1 vWD, 32 with mild haemophilia A and one possible haemophilia A carrier with low FVIII levels was studied. Of these, six were found to have reduced binding (five type 1 vWD, one possible haemophilia A carrier), DNA was extracted from these patients and exons 18-23 of the vWF gene encoding the FVIII binding region of vWF were analysed. After direct sequencing and chemical cleavage mismatch detection, a Thr28Met mutation was detected in two unrelated individuals, one of whom appears to be a compound heterozygote for the mutation and a null allele. No mutations were found in the region of the vWF gene encoding the FVIII binding region of vWF in the other four patients

Von Willebrand disease type 2N: an update

2021 ◽  
Author(s):  
Omid Seidizadeh ◽  
Flora Peyvandi ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Von Willebrand

Recessive von Willebrand Disease Type 2 Normandy: Variable Expression of Mild Hemophilia and VWD Type 1

2009 ◽  
Vol 121 (2-3) ◽  
pp. 119-127 ◽  
Author(s):  
Jan Jacques Michiels ◽  
Alain Gadisseur ◽  
Inge Vangenegten ◽  
Wilfried Schroyens ◽  
Zwi Berneman
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Variable Expression ◽  
Von Willebrand

scholarly journals A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3

2007 ◽  
Vol 5 (4) ◽  
pp. 722-728 ◽  
Author(s):  
R. SCHNEPPENHEIM ◽  
G. CASTAMAN ◽  
A. B. FEDERICI ◽  
W. KREUZ ◽  
R. MARSCHALEK ◽  
...  
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Type 3 ◽  
Von Willebrand
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