Search: onr:"swepub:oai:researchportal.hkr.se/admin:publications/44845f5c-4190-412e-a0fe-2dc92cf7296c" >
Characterization of...
Characterization of large in-frame von Willebrand factor deletions highlights differing pathogenic mechanisms
-
- Cartwright, Ashley (author)
- England
-
- Webster, Simon J (author)
- England
-
- de Jong, Annika (author)
- Netherlands,Nederländerna
-
show more...
-
- Dirven, Richard J (author)
- Netherlands,Nederländerna
-
- Bloomer, Lisa D S (author)
- England
-
- Al-Buhairan, Ahlam M (author)
- England
-
- Budde, Ulrich (author)
- Germany,Tyskland
-
- Halldén, Christer (author)
- Biomedicin
-
- Habart, David (author)
- Czech Republic,Tjeckien
-
- Goudemand, Jenny (author)
- France,Frankrike
-
- Peake, Ian R (author)
- England
-
- Eikenboom, Jeroen C J (author)
- Netherlands,Nederländerna
-
- Goodeve, Anne C (author)
- England
-
- Hampshire, Daniel J (author)
- England
-
show less...
-
(creator_code:org_t)
- 2020-07-01
- 2020
- English 11
-
In: Blood Advances. - : Elsevier BV. - 2473-9529 .- 2473-9537. ; 4:13, s. 2979-2990
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Cartwright, Ashl ...
-
Webster, Simon J
-
de Jong, Annika
-
Dirven, Richard ...
-
Bloomer, Lisa D ...
-
Al-Buhairan, Ahl ...
-
show more...
-
Budde, Ulrich
-
Halldén, Christe ...
-
Habart, David
-
Goudemand, Jenny
-
Peake, Ian R
-
Eikenboom, Jeroe ...
-
Goodeve, Anne C
-
Hampshire, Danie ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Medical Biotechn ...
-
and Biomedical Labor ...
- Articles in the publication
-
Blood Advances
- By the university
-
Kristianstad University College