VWD3
MCID: VNW008
MIFTS: 49

Von Willebrand Disease, Type 3 (VWD3)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Von Willebrand Disease, Type 3

MalaCards integrated aliases for Von Willebrand Disease, Type 3:

Name: Von Willebrand Disease, Type 3 57 44 40 72
Von Willebrand Disease Type 3 12 59 29 6
Vwd3 57 12 74
Von Willebrand Disease, Recessive Form 29 6
Von Willebrand Disease Type Iii 12 74
Von Willibrand Disease, Type 3 57 13
Von Willebrand's Disease 3 12 15
Von Willebrand Factor Deficiency Type 3 74
Von Willebrand Disease Recessive Form 74
Von Willebrand Disease, Type Iii 57
Von Willebrand Disease 3 74
Vwd, Type 3 57
Vwd Type 3 12

Characteristics:

Orphanet epidemiological data:

59
von willebrand disease type 3
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
most severe type of von willebrand disease


HPO:

32
von willebrand disease, type 3:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111054
OMIM 57 277480
MeSH 44 D056729
NCIt 50 C85213
MESH via Orphanet 45 D056729
ICD10 via Orphanet 34 D68.0
UMLS via Orphanet 73 C1264041
Orphanet 59 ORPHA166096
UMLS 72 C1264041

Summaries for Von Willebrand Disease, Type 3

OMIM : 57 Von Willebrand disease is a bleeding disorder resulting from a defect in platelet aggregation due to defects in the von Willebrand factor protein. Type 3 von Willebrand disease, which is inherited as an autosomal recessive disorder, is associated with a severe quantitative defect or virtual absence of VWF in plasma, a prolonged bleeding time, and more severe bleeding tendencies compared to the other types of VWD. Type 3 accounts for about 1% of patients with VWD. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, bleeding after surgery, and hemarthroses. Since VWF also serves as a carrier protein for coagulation factor VIII (F8; 300841), affected individuals also have very low levels of plasma F8, resembling hemophilia A (306700) (summary by 24,21:Zhang et al., 1992, 1993; reviews by Sadler et al., 2006 and Lillicrap, 2009). For a general description and a classification of the types of von Willebrand disease, see VWD type 1 (193400). (277480)

MalaCards based summary : Von Willebrand Disease, Type 3, also known as von willebrand disease type 3, is related to hemophilia and factor viii deficiency. An important gene associated with Von Willebrand Disease, Type 3 is VWF (Von Willebrand Factor), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and ECM-receptor interaction. The drugs Factor VIII and Coagulants have been mentioned in the context of this disorder. Affiliated tissues include endothelial, liver and heart, and related phenotypes are joint hemorrhage and thrombocytopenia

Disease Ontology : 12 A von Willebrand's disease characterized by autosomal recessive inheritance of a severe quantitative defect or virtual absence of VWF in plasma, prolonged bleeding time, and more severe bleeding tendencies compared to the other types of von Willebrand disease that has material basis in homozygous or compound heterozygous mutation in the VWF gene which maps to chromosome 12p13.

UniProtKB/Swiss-Prot : 74 von Willebrand disease 3: A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses.

Related Diseases for Von Willebrand Disease, Type 3

Diseases in the Von Willebrand's Disease family:

Pseudo-Von Willebrand Disease Von Willebrand Disease, Type 1
Von Willebrand Disease, Type 3 Von Willebrand Disease, Type 2
Acquired Von Willebrand Syndrome

Diseases related to Von Willebrand Disease, Type 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 66)
# Related Disease Score Top Affiliating Genes
1 hemophilia 31.3 VWF F8 F3
2 factor viii deficiency 31.0 VWF F8 F11
3 hemophilia a 30.6 VWF F8 F3 F11
4 thrombophilia due to thrombin defect 30.6 VWF F8 F3
5 von willebrand disease, type 1 30.5 VWF GP6 F8 F3
6 von willebrand's disease 30.0 VWF SELP GP1BA F8 F3 F11
7 von willebrand disease, type 2 28.4 VWF GP6 GP1BA F8 F3 DLL1
8 fainting 10.6 VWF F8
9 cerebral arteritis 10.6 VWF F8
10 brachydactyly, type d 10.6 VWF F8
11 hemarthrosis 10.6 VWF F8
12 pseudo-von willebrand disease 10.6 VWF GP1BA
13 fournier gangrene 10.5 F8 F3
14 korean hemorrhagic fever 10.5 VWF F3
15 factor xiii deficiency 10.5 F8 F3
16 intracranial thrombosis 10.4 VWF F8 F3
17 thrombophilia due to activated protein c resistance 10.4 VWF F8 F3
18 platelet aggregation, spontaneous 10.4 VWF SELP
19 giant hemangioma 10.4 F3 DLL1
20 hepatic vascular disease 10.3 VWF F3
21 acquired hemophilia 10.3 F8 F3 F11
22 acquired hemophilia a 10.3 F8 F3 F11
23 lemierre's syndrome 10.3 F3 F11
24 alcohol-related birth defect 10.3 F8 F3 F11
25 hemophilia b 10.3 F8 F3 F11
26 factor x deficiency 10.3 VWF F3 F11
27 carotid artery thrombosis 10.3 SELP F3
28 autoimmune disease of blood 10.2 VWF SELP GP1BA
29 drug-induced lupus erythematosus 10.2 VWF MCAM
30 endocardium disease 10.2 F3 DLL1
31 thrombasthenia 10.2 SELP GP1BA F3
32 qualitative platelet defect 10.2 VWF SELP F3
33 inherited blood coagulation disease 10.2 VWF GP1BA F8 F3
34 bernard-soulier syndrome 10.2 VWF GP1BA F8 CD9
35 factor xi deficiency 10.2 F3 F11
36 grange syndrome 10.2 VWF SELP F3
37 acquired von willebrand syndrome 10.2 VWF GP1BA F8 F11
38 intermediate coronary syndrome 10.2 VWF SELP F3
39 diabetic angiopathy 10.2 VWF IGFBP7
40 thrombotic thrombocytopenic purpura 10.2 VWF SELP F3
41 antiphospholipid syndrome 10.2 VWF SELP F3
42 peripheral vascular disease 10.2 VWF SELP F3
43 afibrinogenemia 10.1 VWF F8 F3 F11
44 arteries, anomalies of 10.1 VWF SELP F3
45 factor v deficiency 10.1 VWF F8 F3 F11
46 thrombophilia 10.1 VWF F8 F3 F11
47 gray platelet syndrome 10.1 VWF SELP GP6
48 acute myocardial infarction 10.1 VWF SELP F3
49 thrombocytopenic purpura, autoimmune 10.1 SELP GP6 GP1BA
50 coronary thrombosis 10.1 VWF GP6 GP1BA F3

Graphical network of the top 20 diseases related to Von Willebrand Disease, Type 3:



Diseases related to Von Willebrand Disease, Type 3

Symptoms & Phenotypes for Von Willebrand Disease, Type 3

Human phenotypes related to Von Willebrand Disease, Type 3:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 joint hemorrhage 32 occasional (7.5%) HP:0005261
2 thrombocytopenia 32 HP:0001873
3 epistaxis 32 HP:0000421
4 bruising susceptibility 32 HP:0000978
5 prolonged bleeding time 32 HP:0003010
6 menorrhagia 32 HP:0000132
7 prolonged bleeding after surgery 32 HP:0004846
8 persistent bleeding after trauma 32 HP:0001934
9 reduced factor viii activity 32 HP:0003125
10 reduced von willebrand factor activity 32 HP:0008330
11 impaired platelet aggregation 32 HP:0003540

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Nose:
epistaxis

Skin Nails Hair Skin:
easy bruising

Laboratory Abnormalities:
severely decreased antigen levels of vwf and factor viii

Hematology:
prolonged bleeding time
menorrhagia
mucocutaneous bleeding
prolonged bleeding after surgery or trauma

Skeletal:
hemarthrosis may occur

Clinical features from OMIM:

277480

MGI Mouse Phenotypes related to Von Willebrand Disease, Type 3:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.81 ATAT1 CD9 DLL1 F3 GP1BA IGFBP7
2 hematopoietic system MP:0005397 9.7 ATAT1 CD9 DLL1 F11 F3 F8
3 immune system MP:0005387 9.28 CD9 DLL1 F11 F3 F8 GP6

Drugs & Therapeutics for Von Willebrand Disease, Type 3

Drugs for Von Willebrand Disease, Type 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Factor VIII Phase 1
2 Coagulants Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Recombinant Von Willebrand Factor / Recombinant Factor VIII Complex (rVWF:rFVIII): A Phase 1 Study Evaluating the Pharmacokinetics (PK), Safety, and Tolerability in Type 3 Von Willebrand Disease (VWD) Completed NCT00816660 Phase 1
2 Type 3 Von Willebrand International Registries Inhibitor Prospective Study Unknown status NCT02460458
3 Study on Von Willebrand Disease and Hemophilia in Cuenca, Ecuador Completed NCT01589848

Search NIH Clinical Center for Von Willebrand Disease, Type 3

Cochrane evidence based reviews: von willebrand disease, type 3

Genetic Tests for Von Willebrand Disease, Type 3

Genetic tests related to Von Willebrand Disease, Type 3:

# Genetic test Affiliating Genes
1 Von Willebrand Disease, Recessive Form 29 VWF
2 Von Willebrand Disease Type 3 29

Anatomical Context for Von Willebrand Disease, Type 3

MalaCards organs/tissues related to Von Willebrand Disease, Type 3:

41
Endothelial, Liver, Heart

Publications for Von Willebrand Disease, Type 3

Articles related to Von Willebrand Disease, Type 3:

(show top 50) (show all 64)
# Title Authors PMID Year
1
A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3. 8 71
19372260 2009
2
Characterization of the genetic defects in recessive type 1 and type 3 von Willebrand disease patients of Italian origin. 8 71
9569178 1998
3
Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands. 8 71
8367445 1993
4
A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients. 8 71
1302613 1992
5
Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. 8 71
1415226 1992
6
Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III. 8 71
1301136 1992
7
Genotype/phenotype association in von Willebrand disease: is the glass half full or empty? 8
19630771 2009
8
von Willebrand Disease 71
20301765 2009
9
The role of molecular genetics in diagnosing von Willebrand disease. 8
19085649 2008
10
Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. 8
16889557 2006
11
Homozygous C2362F von Willebrand factor induces intracellular retention of mutant von Willebrand factor resulting in autosomal recessive severe von Willebrand disease. 71
16643449 2006
12
Patients with type 3 severe von Willebrand disease are not protected against atherosclerosis: results from a multicenter study in 47 patients. 8
14970109 2004
13
Delta C in exon 18 of the von Willebrand gene is uncommon in German vWD type III patients. 71
8165603 1993
14
Autosomal recessive transmission of hemophilia A due to a von Willebrand factor mutation. 8
8500791 1993
15
Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual. 8
2297569 1990
16
Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease. 8
3258663 1988
17
Gene deletions correlate with the development of alloantibodies in von Willebrand disease. 8
3033024 1987
18
A relatively high frequency of severe (type III) von Willebrand's disease in Israel. 8
3082350 1986
19
Recent investigations of the first bleeder family in Aland (Finland) described by von Willebrand. 8
6972630 1981
20
The factor VIII abnormality in severe von Willebrand's disease. 8
315519 1979
21
Classification of von Willebrand's disease. 8
82857 1978
22
Immunoradiometric assay of factor VIII related antigen, with observations in 32 patients with von Willebrand's disease. 8
1083743 1976
23
Detection of heterozygotes in both parents of homozygous patients with Von Willebrand's disease. 8
805164 1975
24
Von Wollebrand's disease with normal Factor VIII activity in a homozygote. 8
4549210 1974
25
'Autosomal haemophilia': a variant of von Willebrand's disease. 8
4546581 1974
26
Detection of heterozygotes for recessive von Willebrand's disease by the assay of antihemophilic-factor-like antigen. 8
4542316 1973
27
Platelets compensate for poor thrombin generation in type 3 von Willebrand disease. 38
30836803 2019
28
The D' domain of von Willebrand factor requires the presence of the D3 domain for optimal factor VIII binding. 38
30111575 2018
29
Liver transplantation in hemophilia A and von Willebrand disease type 3: perioperative management and post-transplant outcome. 38
29931985 2018
30
A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3. 38
29208651 2018
31
Monitoring of coagulation factor therapy in patients with von Willebrand disease type 3 using a microchip flow chamber system. 38
27761577 2017
32
[Von Willebrand disease type 3 falsely diagnosed as hemophilia A: a case report]. 38
28525200 2017
33
Baseline factor VIII plasma levels and age at first bleeding in patients with severe forms of von Willebrand disease. 38
26843468 2016
34
Successful aortic aneurysm repair in a woman with severe von Willebrand (type 3) disease. 38
25960895 2015
35
Germline de novo mutations and linkage markers vs. DNA sequencing for carrier detection in von Willebrand disease. 38
24712919 2014
36
Phenotypic and genotypic characterization of 10 Finnish patients with von Willebrand disease type 3: discovery of two main mutations. 38
23834637 2013
37
Management of von Willebrand disease type 3 during pregnancy - 2 cases reports. 38
24254552 2013
38
Phenotypic and molecular characterisation of type 3 von Willebrand disease in a cohort of Indian patients. 38
23407766 2013
39
Molecular characterization, recombinant protein expression, and mRNA analysis of type 3 von Willebrand disease: Studies of an Italian cohort of 10 patients. 38
22674667 2012
40
Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels. 38
22431567 2012
41
Current management of patients with severe von Willebrand disease type 3: a 2012 update. 38
22722677 2012
42
An unexpected transmission of von Willebrand disease type 3: the first case of maternal uniparental disomy 12. 38
21750090 2011
43
Circulating and progenitor endothelial cells are abnormal in patients with different types of von Willebrand disease and correlate with markers of angiogenesis. 38
21630316 2011
44
Management of inherited von Willebrand disease in Italy: results from the retrospective study on 1234 patients. 38
22102194 2011
45
Spontaneous iliopsoas muscle hematoma in a patient with von Willebrand disease: a case report. 38
21722393 2011
46
A review of long-term prophylaxis in the rare inherited coagulation factor deficiencies. 38
19906159 2010
47
Efficacy and safety of highly purified, doubly virus-inactivated VWF/FVIII concentrates in inherited von Willebrand's disease: results of an Italian cohort study on 120 patients characterized by bleeding severity score. 38
19811543 2010
48
Platelet morphological changes in 2 patients with von Willebrand disease type 3 caused by large homozygous deletions of the von Willebrand factor gene. 38
19608674 2009
49
Clinical and molecular markers of inherited von Willebrand disease type 3: are deletions of the VWF gene associated with alloantibodies to VWF? 38
18853484 2008
50
Genetic defects in von Willebrand disease type 3 in Indian and Greek patients. 38
18485763 2008

Variations for Von Willebrand Disease, Type 3

ClinVar genetic disease variations for Von Willebrand Disease, Type 3:

6 (show all 13)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 VWF NM_000552.4(VWF): c.2561G> A (p.Arg854Gln) single nucleotide variant Pathogenic rs41276738 12:6143978-6143978 12:6034812-6034812
2 VWF NM_000552.4(VWF): c.4975C> T (p.Arg1659Ter) single nucleotide variant Pathogenic rs61750595 12:6127609-6127609 12:6018443-6018443
3 VWF NM_000552.4(VWF): c.5557C> T (p.Arg1853Ter) single nucleotide variant Pathogenic rs61750612 12:6122710-6122710 12:6013544-6013544
4 VWF NM_000552.4(VWF): c.7603C> T (p.Arg2535Ter) single nucleotide variant Pathogenic rs61751296 12:6078503-6078503 12:5969337-5969337
5 VWF NM_000552.4(VWF): c.2435del (p.Pro812fs) deletion Pathogenic rs62643632 12:6153464-6153464 12:6044298-6044298
6 VWF NM_000552.4(VWF): c.7085G> T (p.Cys2362Phe) single nucleotide variant Pathogenic rs61750630 12:6091154-6091154 12:5981988-5981988
7 VWF VWF, 8.6-KB DEL, EX4-5 deletion Pathogenic
8 VWF NM_000552.4(VWF): c.1922C> T (p.Ala641Val) single nucleotide variant Uncertain significance rs61754019 12:6166046-6166046 12:6056880-6056880
9 VWF NM_000552.4(VWF): c.6859C> T (p.Arg2287Trp) single nucleotide variant Uncertain significance rs61750625 12:6094771-6094771 12:5985605-5985605
10 VWF NM_000552.4(VWF): c.7940C> T (p.Thr2647Met) single nucleotide variant Uncertain significance rs61751302 12:6062708-6062708 12:5953542-5953542
11 VWF NM_000552.4(VWF): c.5851A> G (p.Thr1951Ala) single nucleotide variant Uncertain significance rs144072210 12:6105380-6105380 12:5996214-5996214
12 VWF NM_000552.4(VWF): c.1625C> G (p.Ala542Gly) single nucleotide variant Uncertain significance rs141649383 12:6167119-6167119 12:6057953-6057953
13 VWF NM_000552.4(VWF): c.2570A> G (p.Asn857Ser) single nucleotide variant Uncertain significance rs765163545 12:6143969-6143969 12:6034803-6034803

UniProtKB/Swiss-Prot genetic disease variations for Von Willebrand Disease, Type 3:

74
# Symbol AA change Variation ID SNP ID
1 VWF p.Trp377Cys VAR_005782 rs62643626
2 VWF p.Cys2739Tyr VAR_005821 rs61751305
3 VWF p.Pro2063Ser VAR_009142 rs61750615
4 VWF p.Cys2362Phe VAR_009143 rs61750630
5 VWF p.Asn2546Tyr VAR_009144 rs61751298
6 VWF p.Arg273Trp VAR_010242 rs61753997

Expression for Von Willebrand Disease, Type 3

Search GEO for disease gene expression data for Von Willebrand Disease, Type 3.

Pathways for Von Willebrand Disease, Type 3

GO Terms for Von Willebrand Disease, Type 3

Cellular components related to Von Willebrand Disease, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.96 SELP MCAM GP6 GP1BA F8 F3
2 extracellular exosome GO:0070062 9.7 VWF IRF6 IGFBP7 GP6 GP1BA F11
3 extracellular space GO:0005615 9.23 SELP MCAM IGFBP7 GP1BA F8 F3
4 platelet alpha granule membrane GO:0031092 8.96 SELP CD9

Biological processes related to Von Willebrand Disease, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.85 VWF SELP MCAM IGFBP7 GP1BA CD9
2 negative regulation of cell proliferation GO:0008285 9.73 IRF6 IGFBP7 DLL1 CD9
3 platelet activation GO:0030168 9.65 VWF GP6 GP1BA F8 CD9
4 blood coagulation GO:0007596 9.63 VWF GP6 GP1BA F8 F3 F11
5 platelet degranulation GO:0002576 9.62 VWF SELP F8 CD9
6 regulation of blood coagulation GO:0030193 9.4 GP1BA F11
7 blood coagulation, intrinsic pathway GO:0007597 9.26 VWF GP1BA F8 F11
8 hemostasis GO:0007599 9.1 VWF GP6 GP1BA F8 F3 F11

Sources for Von Willebrand Disease, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
Content
Loading form....