OMIA:001058-9823 : Von Willebrand disease III in Sus scrofa (pig)
Categories: Haematopoietic system phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2018
Cross-species summary: The von Willebrand factor (vWF) is a large multimeric plasma glycoprotein required for platelet adhesion and aggregation. A deficiency or defective vWF results in von Willebrand disease (vWD). vWD are often classified in 3 different types based on the clinical severity and quantity and multimere size of von Willebrand factor. Type I is characterized by low plasma vWF concentrations and mild to moderate bleeding symptoms. Type II disorder is characterised by qualitative abnormalities of the vWF protein and moderate to severe bleeding. Type III is the most severe form of vWD with no detectable or a severe quantitative deficiency of vWF.
Molecular basis: Lehner et al. (2018): "a tandem duplication of exons 17 and 18, causing a frameshift and a premature termination codon (p.Val814LeufsTer3) . . . This duplication putatively originates from porcine SINE elements located within VWF introns 16 and 18 with high identity. The premature termination truncates the VWF open reading frame by a large part, resulting in an almost entire loss of the mature peptide. It is therefore supposed to account for the severe VWD type 3."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Allerkamp et al. (2019) reported that "As compared with WT [wild-type], the ovaries of the VWD type 3 animals showed decreased gene expression of ANG2 and increased gene expression of TIE (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains) 2, with some differences in the ANG/TIE-system among the mutant genotypes. In conclusion, severely reduced VWF seems to evoke angiodysplasia in the porcine uterus. Varying distribution and expression of angiogenic factors suggest that this large animal model is promising for investigation of influence of VWF on angiogenesis in larger groups."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|VWF||von Willebrand factor||Sus scrofa||5||NC_010447.5 (64516627..64655938)||VWF||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|969||Mixed breed (duplicate)||Von Willebrand disease III||VWF||duplication||Naturally occurring variant||5||p.(V814Lfs*3)||"a tandem duplication of exons 17 and 18, causing a frameshift and a premature termination codon (p.Val814LeufsTer3) . . . This duplication putatively originates from porcine SINE elements located within VWF introns 16 and 18 with high identity.||2018||29208651|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2021||Arruda, V.R., Weber, J., Samelson-Jones, B.J. :|
|Gene therapy for inherited bleeding disorders. Semin Thromb Hemost 47:161-173, 2021. Pubmed reference: 33636747. DOI: 10.1055/s-0041-1722862.|
|2019||Allerkamp, H., Lehner, S., Ekhlasi-Hundrieser, M., Detering, C., von Depka Prondzinski, M., Pfarrer, C. :|
|Expression of angiogenic factors in the uteroplacental unit is altered at time of placentation in a porcine model of von Willebrand disease type 1. Reprod Biol 19:412-420, 2019. Pubmed reference: 31806575. DOI: 10.1016/j.repbio.2019.09.007.|
|Allerkamp, H., Lehner, S., Ekhlasi-Hundrieser, M., Detering, C., Pfarrer, C., Depka Prondzinski, M.V. :|
|Characterization of a Porcine Model for Von Willebrand Disease Type 1 and 3 Regarding Expression of Angiogenic Mediators in the Nonpregnant Female Reproductive Tract. Comp Med 69:401-412, 2019. Pubmed reference: 31526432. DOI: 10.30802/AALAS-CM-19-000003.|
|2018||Lehner, S., Ekhlasi-Hundrieser, M., Detering, C., Allerkamp, H., Pfarrer, C., von Depka Prondzinski, M. :|
|A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3. G3 (Bethesda) 8:577-585, 2018. Pubmed reference: 29208651. DOI: 10.1534/g3.117.300432.|
|1999||Denis, C.V., Wagner, D.D. :|
|Insights from von Willebrand disease animal models. Cell Mol Life Sci 56:977-90, 1999. Pubmed reference: 11212329. DOI: 10.1007/s000180050487.|
- Created by Frank Nicholas on 03 Feb 2018
- Changed by Frank Nicholas on 03 Feb 2018
- Changed by Frank Nicholas on 20 Sep 2019
- Changed by Imke Tammen2 on 28 Aug 2021
- Changed by Imke Tammen2 on 10 Sep 2021