Source:http://linkedlifedata.com/resource/pubmed/id/18064311
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2007-12-7
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| pubmed:abstractText |
Mutations in the A1 domain of von Willebrand factor (VWF) may be associated with gain of function in the VWF-platelet GPIb interaction and consumption of large VWF multimers, as seen in type 2B von Willebrand disease (VWD). We report a new VWF abnormality associated with greater VWF-GPIb interaction in the presence of all VWF multimers. The index case is a woman with a lifelong history of bleeding, found hyperresponsive to ristocetin with spontaneous platelet aggregation (SPA). She had normal factor VIII, VWF:Ag, VWF:RCo and VWF:CB levels, normal VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios, and a full panel of plasma and platelet VWF multimers. A missense mutation (4115T>G) was found in exon 28 of the VWF gene, which replaced a isoleucine with a serine at position 1372 of pre-pro-VWF (I1372S) at heterozygous level. Recombinant VWF carrying the I1372S mutation and showing a normal VWF multimer organisation was capable of inducing SPA on normal platelet-rich plasma (unlike wild-type VWF), as well as a hyper-response to ristocetin in the same platelets (0.6 mg/ml ristocetin vs. 1.2 of wild-type VWF). The new I1372S VWF mutation, characterized by SPA and hyper-responsiveness to ristocetin thus has some of the features of type 2B VWD, but not the lack of large VWF multimers, so we defined this variant as type 2B-like VWD. Why I1372S VWF is associated with bleeding symptoms, despite normal VWF levels and multimer organisation, remains to be seen.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
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| pubmed:issn |
0340-6245
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
98
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1182-7
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:18064311-Adult,
pubmed-meshheading:18064311-Animals,
pubmed-meshheading:18064311-Blood Platelets,
pubmed-meshheading:18064311-Cell Line,
pubmed-meshheading:18064311-Cricetinae,
pubmed-meshheading:18064311-DNA Mutational Analysis,
pubmed-meshheading:18064311-Exons,
pubmed-meshheading:18064311-Female,
pubmed-meshheading:18064311-Genotype,
pubmed-meshheading:18064311-Hemorrhage,
pubmed-meshheading:18064311-Humans,
pubmed-meshheading:18064311-Mutation, Missense,
pubmed-meshheading:18064311-Pedigree,
pubmed-meshheading:18064311-Phenotype,
pubmed-meshheading:18064311-Platelet Aggregation,
pubmed-meshheading:18064311-Platelet Function Tests,
pubmed-meshheading:18064311-Platelet Glycoprotein GPIb-IX Complex,
pubmed-meshheading:18064311-Protein Structure, Quaternary,
pubmed-meshheading:18064311-Protein Structure, Tertiary,
pubmed-meshheading:18064311-Ristocetin,
pubmed-meshheading:18064311-Transfection,
pubmed-meshheading:18064311-von Willebrand Diseases,
pubmed-meshheading:18064311-von Willebrand Factor
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| pubmed:year |
2007
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| pubmed:articleTitle |
A novel von Willebrand factor mutation (I1372S) associated with type 2B-like von Willebrand disease: an elusive phenotype and a difficult diagnosis.
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| pubmed:affiliation |
University of Padua, Medical School, Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, Padua, Italy. sandra.casonato@unipd.it
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| pubmed:publicationType |
Journal Article,
Case Reports
|