Results of a Screening for von Willebrand Disease Type 2N in Patients with Suspected Haemophilia A or von Willebrand Disease Type 1
Results of a Screening for von Willebrand Disease Type 2N in Patients with Suspected Haemophilia A or von Willebrand Disease Type 1
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对疑似 A 型血友病或 1 型冯维勒布兰德病患者进行 2N 型冯维勒布兰德病筛查结果
DOI：
10.1055/s-0038-1650628
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发表时间：
1996
影响因子：
6.7
通讯作者：
R. Schwaab
中科院分区：
文献类型：
--
作者：
R. Schneppenheim;U. Budde;S. Krey;E. Drewke;F. Bergmann;Eberhard Lechler;J. Oldenburg;R. Schwaab
Summary A 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.
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主要因子 VIII 结合域位于冯·维勒布兰德因子的氨基末端 272 个氨基酸残基内。
DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Foster,PA;Fulcher,CA;Marti,T;Titani,K;Zimmerman,TS
通讯作者：
Zimmerman,TS
在一种变异形式的冯·维勒布兰德病中，因子 VIII 的异常结合与冯·维勒布兰德因子中谷氨酰胺取代精氨酸 91 有关。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kroner,PA;Friedman,KD;Fahs,SA;Scott,JP;Montgomery,RR
通讯作者：
Montgomery,RR
影响因子：
9.8
作者：
B. Budowle;R. Chakraborty;A. Giusti;A. Eisenberg;R. Allen
通讯作者：
B. Budowle;R. Chakraborty;A. Giusti;A. Eisenberg;R. Allen
独特的冯·维勒布兰德病变体的分子特征。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Cacheris,PM;Nichols,WC;Ginsburg,D
通讯作者：
Ginsburg,D