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Characterization of...
Characterization of large in-frame von Willebrand factor deletions highlights differing pathogenic mechanisms
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- Cartwright, Ashley (författare)
- England
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- Webster, Simon J (författare)
- England
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- de Jong, Annika (författare)
- Netherlands,Nederländerna
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visa fler...
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- Dirven, Richard J (författare)
- Netherlands,Nederländerna
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- Bloomer, Lisa D S (författare)
- England
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- Al-Buhairan, Ahlam M (författare)
- England
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- Budde, Ulrich (författare)
- Germany,Tyskland
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- Halldén, Christer (författare)
- Biomedicin
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- Habart, David (författare)
- Czech Republic,Tjeckien
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- Goudemand, Jenny (författare)
- France,Frankrike
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- Peake, Ian R (författare)
- England
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- Eikenboom, Jeroen C J (författare)
- Netherlands,Nederländerna
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- Goodeve, Anne C (författare)
- England
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- Hampshire, Daniel J (författare)
- England
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(creator_code:org_t)
- 2020-07-01
- 2020
- Engelska 11
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Ingår i: Blood Advances. - : Elsevier BV. - 2473-9529 .- 2473-9537. ; 4:13, s. 2979-2990
- Relaterad länk:
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https://doi.org/10.1...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Copy number variation (CNV) is known to cause all von Willebrand disease (VWD) types, although the associated pathogenic mechanisms involved have not been extensively studied. Notably, in-frame CNV provides a unique opportunity to investigate how specific von Willebrand factor (VWF) domains influence the processing and packaging of the protein. Using multiplex ligation-dependent probe amplification, this study determined the extent to which CNV contributed to VWD in the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease cohort, highlighting in-frame deletions of exons 3, 4-5, 32-34, and 33-34. Heterozygous in vitro recombinant VWF expression demonstrated that, although deletion of exons 3, 32-34, and 33-34 all resulted in significant reductions in total VWF (P < .0001, P < .001, and P < .01, respectively), only deletion of exons 3 and 32-34 had a significant impact on VWF secretion (P < .0001). High-resolution microscopy of heterozygous and homozygous deletions confirmed these observations, indicating that deletion of exons 3 and 32-34 severely impaired pseudo-Weibel-Palade body (WPB) formation, whereas deletion of exons 33-34 did not, with this variant still exhibiting pseudo-WPB formation similar to wild-type VWF. In-frame deletions in VWD, therefore, contribute to pathogenesis via moderate or severe defects in VWF biosynthesis and secretion.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Cartwright, Ashl ...
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Webster, Simon J
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de Jong, Annika
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Dirven, Richard ...
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Bloomer, Lisa D ...
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Al-Buhairan, Ahl ...
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visa fler...
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Budde, Ulrich
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Halldén, Christe ...
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Habart, David
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Goudemand, Jenny
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Peake, Ian R
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Eikenboom, Jeroe ...
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Goodeve, Anne C
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Hampshire, Danie ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Biomedicinsk lab ...
- Artiklar i publikationen
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Blood Advances
- Av lärosätet
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Högskolan Kristianstad