The inheritance and molecular genetics of von Willebrand's disease

Eikenboom, Jeroen; Reitsma, Pieter H.; Briët, E.

doi:10.1111/j.1365-2516.1995.tb00045.x

Cited by 8 publications

(8 citation statements)

References 142 publications

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“…Human vWF is a large multimeric glycoprotein that plays an essential role in the adhesion of platelets to the subendothelium under the high shear stress that is prevalent in the microcirculation of the blood. It also acts as a carrier for coagulation factor VIII [2]. The vWF cDNA was cloned by several groups simultaneously between 1985 and 1986.…”

Section: Introductionmentioning

confidence: 99%

Search for mutations in a segment of the exon 28 of the human von Willebrand factor gene: New mutations, R1315C and R1341W, associated with type 2M and 2B variants

Casaña

Martı́nez²,

Espinós

et al. 1998

Am. J. Hematol.

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von Willebrand Disease (vWD) is the most frequently inherited bleeding disorder in humans, and is caused by a qualitative and/or quantitative abnormality of the von Willebrand factor (vWF). A large number of defects that cause qualitative variants have been located in the A1 domain of the vWF, which contains sites for interaction with platelet glycoprotein Ib (GPIb). We have developed a new approach to detect mutations based on DdeI digestion and single-strand conformation polymorphism analysis. A segment of 487 nucleotides, extending from intron 27 to codon 1368 of the pre-pro vWF was amplified from genomic DNA. The cleavage with DdeI yields two fragments of appropriate size for this kind of analysis and confirms that the gene, rather than the pseudogene, is being investigated. Six families with type 2B vWD, one type 2M vWD family, and one another type 2A vWD family were studied. After sequencing the fragments with an altered electrophoretic pattern, we found four mutations previously described--R1308C, V1316M, P1337L, and R1306W--in patients with 2B vWD. The last one arose de novo in the patient. In addition, two new candidate mutations were observed: R1315C and R1341W. The first one was associated to type 2M vWD, whereas the one second cosegregated with type 2B vWD. The fact that these new mutations were not found in 100 normal alleles screened further supports their causal relationship with the disease. These mutations, which induce either a gain or a loss of function, further show an important regulatory role of this region in the binding of vWF to GPIb and its implications in causing disease.

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Section: Introductionmentioning

confidence: 99%

Search for mutations in a segment of the exon 28 of the human von Willebrand factor gene: New mutations, R1315C and R1341W, associated with type 2M and 2B variants

Casaña

Martı́nez²,

Espinós

et al. 1998

Am. J. Hematol.

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“…14 Both fibrinogen and von Willebrand factor are essential to platelet aggregation, and pathologic alterations in these proteins can lead to either increased or decreased platelet aggregation. [15][16][17] Platelet aggregation and adherence are not only important in the evolution and progression of an atherosclerotic plaque, but can also initiate the occurrence of a myocardial infarction (MI) through the formation of an occlusive thrombus at the site of a ruptured plaque. 18,19 Genetic changes in the genes encoding either for ecNOS or the GPIIb/IIIa receptor could contribute to the development of CAD.…”

mentioning

confidence: 99%

The Relationship Between Polymorphisms in the Endothelial Cell Nitric Oxide Synthase Gene and the Platelet GPIIIa Gene With Myocardial Infarction and Venous Thromboembolism in African Americans

Hooper

Lally

Austin

et al. 1999

Chest

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“…It should be noted that a similar observation by Nichols et al. (1991) was a misinterpretation due to the presence of a previously unknown VWF gene polymorphism in the primer sequence which abolished amplification of one allele (Eikenboom et al., 1995).…”

Section: Type 3 Vwdmentioning

confidence: 83%

“…A range of nonsense and frameshift mutations, predicted to result in loss of VWF protein expression, or expression of a truncated protein, have been identified in type 3 VWD families (Bahnak et al., 1991; Eikenboom et al., 1992; Zhang et al., 1992a; Zhang et al., 1992b; Schneppenheim et al., 1994; Zhang et al., 1994; Eikenboom et al., 1995; Eikenboom et al., 1998; Abuzenadah et al., 1999; Baronciani et al., 2000; Casana et al., 2000; Schneppenheim et al., 2000). Several type 3 VWD patients have been shown to be homozygous or compound heterozygous for candidate missense mutations in the VWF gene (Schneppenheim et al., 1994; Zhang et al., 1994; Zhang et al., 1995; Eikenboom et al., 1998).…”

Section: Type 3 Vwdmentioning

confidence: 99%

The molecular biology of von Willebrand disease

Keeney¹,

Cumming²

2001

Clinical &Amp; Laboratory Haematology

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Summary von Willebrand disease (VWD) is a common autosomally inherited bleeding disorder associated with mucosal or trauma-related bleeding in affected individuals. VWD results from either a quantitative or qualitative de®ciency of von Willebrand factor (VWF) ± a glycoprotein with essential roles in primary haemostasis and as a carrier of coagulation factor VIII (FVIII) in the circulation. In recent years the identi®cation of mutations in the VWF gene in patients with VWD has improved our understanding of the structure and function of the VWF protein, and has illustrated the importance of speci®c regions of VWF for its interaction with other components of the vasculature. The underlying genetic lesions and associated molecular pathology have been identi®ed in many cases of type 2A, type 2B, type 2M, type 2N and type 3 VWD. However in the most common variant, type 1 VWD, the causative molecular defect is unknown in the large majority of cases. In the absence of an understanding of the molecular pathology underlying type 1 VWD, precise diagnosis and classi®cation of this common disorder remains problematic.

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The inheritance and molecular genetics of von Willebrand's disease

Cited by 8 publications

References 142 publications

Search for mutations in a segment of the exon 28 of the human von Willebrand factor gene: New mutations, R1315C and R1341W, associated with type 2M and 2B variants

Search for mutations in a segment of the exon 28 of the human von Willebrand factor gene: New mutations, R1315C and R1341W, associated with type 2M and 2B variants

The Relationship Between Polymorphisms in the Endothelial Cell Nitric Oxide Synthase Gene and the Platelet GPIIIa Gene With Myocardial Infarction and Venous Thromboembolism in African Americans

The molecular biology of von Willebrand disease

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