MCID: ATS208
MIFTS: 32

Autosomal Dominant Macrothrombocytopenia

Categories: Blood diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Autosomal Dominant Macrothrombocytopenia

MalaCards integrated aliases for Autosomal Dominant Macrothrombocytopenia:

Name: Autosomal Dominant Macrothrombocytopenia 58 29

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant macrothrombocytopenia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide);

Classifications:

Orphanet: 58  
Rare haematological diseases


External Ids:

ICD10 via Orphanet 33 D69.4
Orphanet 58 ORPHA140957

Summaries for Autosomal Dominant Macrothrombocytopenia

MalaCards based summary : Autosomal Dominant Macrothrombocytopenia is related to myh-9 related disease and thrombocytopenia due to platelet alloimmunization. An important gene associated with Autosomal Dominant Macrothrombocytopenia is TUBB1 (Tubulin Beta 1 Class VI), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Sertoli-Sertoli Cell Junction Dynamics. Affiliated tissues include neutrophil, and related phenotype is hematopoietic system.

Related Diseases for Autosomal Dominant Macrothrombocytopenia

Diseases in the Autosomal Dominant Macrothrombocytopenia family:

Macrothrombocytopenia, Autosomal Dominant, Tubb1-Related

Diseases related to Autosomal Dominant Macrothrombocytopenia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 49)
# Related Disease Score Top Affiliating Genes
1 myh-9 related disease 29.8 MYH9 GP1BB GP1BA ACTN1
2 thrombocytopenia due to platelet alloimmunization 29.8 ITGB3 ITGA2B GP1BA
3 blood platelet disease 29.4 MYH9 ITGB3 ITGA2B GP1BB GP1BA
4 thrombasthenia 29.3 ITGB3 ITGA2B GP1BA EFCAB13-DT
5 glanzmann thrombasthenia 1 29.3 ITGB3 ITGA2B GP1BA EFCAB13-DT
6 bernard-soulier syndrome 29.0 TUBB1 MYH9 ITGB3 ITGA2B GP1BB GP1BA
7 thrombocytopenia 28.1 TUBB1 MYH9 ITGB3 ITGA2B GP1BB GP1BA
8 macrothrombocytopenia, autosomal dominant, tubb1-related 11.4
9 bleeding disorder, platelet-type, 15 11.3
10 bleeding disorder, platelet-type, 17 11.2
11 macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss 10.3
12 cataract 10.2
13 branchiootic syndrome 1 10.2
14 arteritic anterior ischemic optic neuropathy 10.1 ITGB3 GP1BA
15 acrokeratoderma, hereditary papulotranslucent 10.0 GP1BB GP1BA
16 bleeding disorder, platelet-type, 24 10.0 ITGB3 EFCAB13-DT
17 pseudo-von willebrand disease 10.0 GP1BB GP1BA
18 glanzmann thrombasthenia 2 10.0 ITGB3 EFCAB13-DT
19 bernard-soulier syndrome, type a2, autosomal dominant 10.0
20 triiodothyronine receptor auxiliary protein 10.0
21 sitosterolemia 1 10.0
22 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
23 sensorineural hearing loss 10.0
24 glomerular disease 10.0
25 carotid artery thrombosis 10.0 ITGA2B GP1BA
26 bleeding disorder, platelet-type, 11 9.9 ITGA2B GP1BA
27 intracranial thrombosis 9.9 ITGA2B GP1BA
28 autoimmune disease of blood 9.9 ITGB3 ITGA2B
29 primary thrombocytopenia 9.9 ITGB3 ITGA2B GP1BA
30 coronary thrombosis 9.8 ITGB3 ITGA2B GP1BA
31 thrombosis 9.8 ITGB3 ITGA2B GP1BA
32 thrombocytopenic purpura, autoimmune 9.8 ITGB3 ITGA2B GP1BA
33 purpura 9.8 ITGB3 ITGA2B GP1BA
34 myeloproliferative syndrome, transient 9.8 ITGB3 ITGA2B GP1BA
35 acute megakaryocytic leukemia 9.8 ITGB3 ITGA2B GP1BA
36 sickle cell anemia 9.8 ITGB3 ITGA2B GP1BA
37 von willebrand's disease 9.8 ITGA2B GP1BA
38 infective endocarditis 9.8 ITGB3 GP1BA
39 bleeding disorder, platelet-type, 16 9.8 ITGB3 ITGA2B EFCAB13-DT
40 arteriosclerosis 9.7 ITGB3 ITGA2B GP1BA
41 essential thrombocythemia 9.7 ITGB3 ITGA2B GP1BA
42 thrombocytopenia-absent radius syndrome 9.7 GP1BB GFI1B ACTN1
43 cerebrovascular disease 9.7 ITGB3 ITGA2B GP1BA
44 acquired thrombocytopenia 9.7 MYH9 ITGA2B GP1BB GP1BA
45 fetal and neonatal alloimmune thrombocytopenia 9.6 ITGB3 ITGA2B GP1BB GP1BA
46 gray platelet syndrome 9.6 MYH9 ITGA2B GFI1B
47 blood coagulation disease 9.5 MYH9 ITGB3 ITGA2B GP1BB GP1BA
48 aplastic anemia 9.3 ITGB3 ITGA2B GP1BA GFI1B
49 hemorrhagic disease 9.1 TUBB1 MYH9 ITGB3 ITGA2B GP1BA GFI1B

Graphical network of the top 20 diseases related to Autosomal Dominant Macrothrombocytopenia:



Diseases related to Autosomal Dominant Macrothrombocytopenia

Symptoms & Phenotypes for Autosomal Dominant Macrothrombocytopenia

MGI Mouse Phenotypes related to Autosomal Dominant Macrothrombocytopenia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.17 GFI1B GP1BA GP1BB ITGA2B ITGB3 MYH9

Drugs & Therapeutics for Autosomal Dominant Macrothrombocytopenia

Search Clinical Trials , NIH Clinical Center for Autosomal Dominant Macrothrombocytopenia

Genetic Tests for Autosomal Dominant Macrothrombocytopenia

Genetic tests related to Autosomal Dominant Macrothrombocytopenia:

# Genetic test Affiliating Genes
1 Autosomal Dominant Macrothrombocytopenia 29

Anatomical Context for Autosomal Dominant Macrothrombocytopenia

MalaCards organs/tissues related to Autosomal Dominant Macrothrombocytopenia:

40
Neutrophil

Publications for Autosomal Dominant Macrothrombocytopenia

Articles related to Autosomal Dominant Macrothrombocytopenia:

(show all 32)
# Title Authors PMID Year
1
Novel ACTN1 variants in cases of thrombocytopenia. 6
31237726 2019
2
ACTN1 mutations cause congenital macrothrombocytopenia. 6
23434115 2013
3
Glanzmann thrombasthenia-like syndromes associated with Macrothrombocytopenias and mutations in the genes encoding the αIIbβ3 integrin. 6
22102273 2011
4
Heterozygous ITGA2B R995W mutation inducing constitutive activation of the αIIbβ3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia. 6
21454453 2011
5
Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly. 6
18849486 2009
6
R to Q amino acid substitution in the GFFKR sequence of the cytoplasmic domain of the integrin IIb subunit in a patient with a Glanzmann's thrombasthenia-like syndrome. 6
9834222 1998
7
A defect of platelet aggregation associated with an abnormal distribution of glycoprotein IIb-IIIa complexes within the platelet: the cause of a lifelong bleeding disorder. 6
1638023 1992
8
DIAPH1 Mutation as a Novel Cause of Autosomal Dominant Macrothrombocytopenia and Hearing Loss. 61
32594080 2021
9
Autosomal dominant macrothrombocytopenia caused by a rare GPIBB variant: The importance of DNA sequencing. 61
31793234 2020
10
αIIbβ3 variants in ten families with autosomal dominant macrothrombocytopenia: Expanding the mutational and clinical spectrum. 61
33276370 2020
11
A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome. 61
30332551 2018
12
ACTN1 mutations lead to a benign form of platelet macrocytosis not always associated with thrombocytopenia. 61
30351444 2018
13
A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction. 61
29380037 2018
14
Eltrombopag to Treat Thrombocytopenia During Last Month of Pregnancy in a Woman With MYH9-Related Disease: A Case Report. 61
28795988 2018
15
Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia. 61
28064200 2017
16
ACTN1 rod domain mutation associated with congenital macrothrombocytopenia. 61
26453073 2016
17
A missense mutation in the alpha-actinin 1 gene (ACTN1) is the cause of autosomal dominant macrothrombocytopenia in a large French family. 61
24069336 2013
18
Dominant inheritance of a novel integrin beta3 mutation associated with a hereditary macrothrombocytopenia and platelet dysfunction in two Italian families. 61
19336737 2009
19
[Autosomal dominant macrothrombocytopenia with leukocyte inclusion bodies and MYH9 disorders]. 61
19489439 2009
20
[May-Hegglin anomaly: past and present--novel diagnostic test and new concept of the disease]. 61
19227191 2009
21
Acute myeloid leukemia in a child with hereditary thrombocytopenia. 61
16276527 2007
22
Sebastian platelet syndrome: a hereditary macrothrombocytopenia. 61
14601703 2003
23
[May-Hegglin anomaly--from genome research to clinical laboratory]. 61
14560660 2003
24
Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations. 61
12533692 2003
25
Autosomal dominant macrothrombocytopenia with ineffective thrombopoiesis. 61
12010687 2002
26
Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome. 61
11222377 2001
27
Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome). 61
11159552 2001
28
Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions. 61
11776386 2001
29
Autosomal-dominant giant platelet syndromes: a hint of the same genetic defect as in Fechtner syndrome owing to a similar genetic linkage to chromosome 22q11-13. 61
11071640 2000
30
Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. 61
10973260 2000
31
Autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly) is linked to chromosome 22q12-13. 61
10914687 2000
32
Platelet kinetics in autosomal dominant macrothrombocytopenia. 61
9626983 1998

Variations for Autosomal Dominant Macrothrombocytopenia

ClinVar genetic disease variations for Autosomal Dominant Macrothrombocytopenia:

6 (show all 32)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ACTN1 NM_001102.4(ACTN1):c.2212C>T (p.Arg738Trp) SNV Pathogenic 42032 rs387907349 GRCh37: 14:69346747-69346747
GRCh38: 14:68880030-68880030
2 ACTN1 NM_001102.4(ACTN1):c.673G>A (p.Glu225Lys) SNV Pathogenic 42033 rs387907350 GRCh37: 14:69371375-69371375
GRCh38: 14:68904658-68904658
3 TUBB1 NM_030773.3(TUBB1):c.952C>T (p.Arg318Trp) SNV Pathogenic 425 rs121918555 GRCh37: 20:57599434-57599434
GRCh38: 20:59024379-59024379
4 ACTN1 NM_001102.4(ACTN1):c.313G>A (p.Val105Ile) SNV Pathogenic 42028 rs387907345 GRCh37: 14:69387750-69387750
GRCh38: 14:68921033-68921033
5 ACTN1 NM_001102.4(ACTN1):c.94C>A (p.Gln32Lys) SNV Pathogenic 42029 rs387907346 GRCh37: 14:69445680-69445680
GRCh38: 14:68978963-68978963
6 ACTN1 NM_001102.4(ACTN1):c.2255G>A (p.Arg752Gln) SNV Pathogenic 42030 rs387907347 GRCh37: 14:69346704-69346704
GRCh38: 14:68879987-68879987
7 ITGA2B NM_000419.5(ITGA2B):c.3077G>A (p.Arg1026Gln) SNV Pathogenic 50232 rs879255514 GRCh37: 17:42449775-42449775
GRCh38: 17:44372407-44372407
8 TUBB1 NM_030773.3(TUBB1):c.779T>C (p.Phe260Ser) SNV Pathogenic 372810 rs1057517996 GRCh37: 20:57599261-57599261
GRCh38: 20:59024206-59024206
9 EFCAB13-DT , ITGB3 NM_000212.2(ITGB3):c.2248C>T (p.Arg750Ter) SNV Pathogenic 13564 rs121918450 GRCh37: 17:45384950-45384950
GRCh38: 17:47307584-47307584
10 ITGA2B NM_000419.5(ITGA2B):c.3076C>T (p.Arg1026Trp) SNV Pathogenic 50233 rs766503255 GRCh37: 17:42449776-42449776
GRCh38: 17:44372408-44372408
11 TUBB1 NM_030773.4(TUBB1):c.57+1G>A SNV Likely pathogenic 1028901 GRCh37: 20:57594635-57594635
GRCh38: 20:59019580-59019580
12 ITGB3 NM_000212.2(ITGB3):c.1699C>T (p.Gln567Ter) SNV Likely pathogenic 374015 rs1057518837 GRCh37: 17:45376682-45376682
GRCh38: 17:47299316-47299316
13 ITGB3 NM_000212.2(ITGB3):c.749A>G (p.Asp250Gly) SNV Likely pathogenic 374016 rs1057518838 GRCh37: 17:45363760-45363760
GRCh38: 17:47286394-47286394
14 ACTN1 NM_001102.4(ACTN1):c.137G>A (p.Arg46Gln) SNV Likely pathogenic 42031 rs387907348 GRCh37: 14:69392358-69392358
GRCh38: 14:68925641-68925641
15 ACTN1 NM_001102.4(ACTN1):c.2201A>G (p.Gln734Arg) SNV Likely pathogenic 517137 rs1555343284 GRCh37: 14:69346758-69346758
GRCh38: 14:68880041-68880041
16 ACTN1 NM_001102.4(ACTN1):c.770C>G (p.Thr257Arg) SNV Likely pathogenic 627135 rs1594773549 GRCh37: 14:69360457-69360457
GRCh38: 14:68893740-68893740
17 ACTN1 NM_001130004.1(ACTN1):c.970A>G (p.Lys324Glu) SNV Likely pathogenic 666541 rs1594771270 GRCh37: 14:69358886-69358886
GRCh38: 14:68892169-68892169
18 ACTN1 NM_001130004.1(ACTN1):c.982G>A (p.Val328Met) SNV Likely pathogenic 666542 rs1594771236 GRCh37: 14:69358874-69358874
GRCh38: 14:68892157-68892157
19 ACTN1 NM_001130004.1(ACTN1):c.986A>G (p.Gln329Arg) SNV Likely pathogenic 666543 rs1594771224 GRCh37: 14:69358870-69358870
GRCh38: 14:68892153-68892153
20 ACTN1 NM_001130004.1(ACTN1):c.1193A>C (p.Lys398Thr) SNV Likely pathogenic 666544 rs1594768463 GRCh37: 14:69356897-69356897
GRCh38: 14:68890180-68890180
21 ACTN1 NM_001130004.1(ACTN1):c.1295C>T (p.Ala432Val) SNV Likely pathogenic 666545 rs1594760140 GRCh37: 14:69352232-69352232
GRCh38: 14:68885515-68885515
22 ACTN1 NM_001130004.1(ACTN1):c.1348C>T (p.Arg450Cys) SNV Likely pathogenic 666546 rs1594760036 GRCh37: 14:69352179-69352179
GRCh38: 14:68885462-68885462
23 ACTN1 NM_001130004.1(ACTN1):c.1349G>A (p.Arg450His) SNV Likely pathogenic 666547 rs751173836 GRCh37: 14:69352178-69352178
GRCh38: 14:68885461-68885461
24 ACTN1 NM_001130004.1(ACTN1):c.1864C>T (p.His622Tyr) SNV Likely pathogenic 666548 rs1594755688 GRCh37: 14:69349264-69349264
GRCh38: 14:68882547-68882547
25 ACTN1 NM_001130004.1(ACTN1):c.2157G>C (p.Gln719His) SNV Likely pathogenic 666549 rs1594751825 GRCh37: 14:69346802-69346802
GRCh38: 14:68880085-68880085
26 ACTN1 NM_001130004.1(ACTN1):c.2243T>A (p.Met748Lys) SNV Likely pathogenic 666550 rs1594751659 GRCh37: 14:69346716-69346716
GRCh38: 14:68879999-68879999
27 ITGA2B NM_000419.5(ITGA2B):c.2965G>A (p.Ala989Thr) SNV Uncertain significance 417951 rs78165611 GRCh37: 17:42451817-42451817
GRCh38: 17:44374449-44374449
28 ITGA2B NM_000419.5(ITGA2B):c.1043G>A (p.Arg348Gln) SNV Uncertain significance 417956 rs1060499614 GRCh37: 17:42461028-42461028
GRCh38: 17:44383660-44383660
29 ITGB3 NM_000212.2(ITGB3):c.1960G>A (p.Glu654Lys) SNV Uncertain significance 225395 rs70940817 GRCh37: 17:45377890-45377890
GRCh38: 17:47300524-47300524
30 ITGA2B NM_000419.5(ITGA2B):c.1142C>T (p.Thr381Ile) SNV Uncertain significance 1030779 GRCh37: 17:42460929-42460929
GRCh38: 17:44383561-44383561
31 ITGA2B NM_000419.5(ITGA2B):c.1752+5G>A SNV Uncertain significance 1030780 GRCh37: 17:42457365-42457365
GRCh38: 17:44379997-44379997
32 TUBB1 NM_030773.3(TUBB1):c.326G>A (p.Gly109Glu) SNV Uncertain significance 626929 rs41303899 GRCh37: 20:57598808-57598808
GRCh38: 20:59023753-59023753

Expression for Autosomal Dominant Macrothrombocytopenia

Search GEO for disease gene expression data for Autosomal Dominant Macrothrombocytopenia.

Pathways for Autosomal Dominant Macrothrombocytopenia

Pathways related to Autosomal Dominant Macrothrombocytopenia according to GeneCards Suite gene sharing:

(show all 24)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13 ITGB3 ITGA2B GP1BB GP1BA ACTN1
2
Show member pathways
12.56 TUBB1 MYH9 ITGB3 ITGA2B ACTN1
3
Show member pathways
12.32 MYH9 ITGB3 ACTN1
4 12.3 MYH9 ITGB3 ITGA2B ACTN1
5
Show member pathways
12.28 MYH9 ITGB3 ACTN1
6 12.27 MYH9 ITGA2B ACTN1
7
Show member pathways
11.98 TPM4 ITGB3 ITGA2B
8 11.86 ITGB3 ITGA2B ACTN1
9
Show member pathways
11.75 ITGB3 ITGA2B GP1BB GP1BA
10 11.7 ITGB3 ITGA2B GP1BA
11 11.55 ITGB3 ITGA2B GP1BB GP1BA
12 11.37 ITGB3 ITGA2B
13 11.3 ITGB3 ITGA2B
14 11.28 MYH9 ITGB3 ITGA2B
15 11.27 ITGB3 ITGA2B
16 11.25 ITGB3 ITGA2B GP1BB GP1BA
17 11.21 ITGB3 ITGA2B GP1BB
18 11.18 ITGB3 ACTN1
19 11.1 ITGB3 ITGA2B
20 10.98 ITGB3 ITGA2B
21
Show member pathways
10.92 ITGB3 ITGA2B GP1BB GP1BA
22 10.83 ITGB3 ITGA2B
23 10.59 GP1BB GP1BA
24 10.4 GP1BB GP1BA

GO Terms for Autosomal Dominant Macrothrombocytopenia

Cellular components related to Autosomal Dominant Macrothrombocytopenia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.7 TUBB1 TPM4 MYH9 ITGB3 ITGA2B GP1BA
2 brush border GO:0005903 9.37 MYH9 ACTN1
3 integrin complex GO:0008305 9.32 ITGB3 ITGA2B
4 platelet alpha granule membrane GO:0031092 9.26 ITGB3 ITGA2B
5 stress fiber GO:0001725 9.13 TPM4 MYH9 ACTN1
6 focal adhesion GO:0005925 9.02 TPM4 MYH9 ITGB3 ITGA2B ACTN1

Biological processes related to Autosomal Dominant Macrothrombocytopenia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 blood coagulation GO:0007596 9.61 ITGB3 GP1BB GP1BA
2 cell adhesion GO:0007155 9.55 MYH9 ITGB3 ITGA2B GP1BB GP1BA
3 platelet degranulation GO:0002576 9.5 ITGB3 ITGA2B ACTN1
4 hemostasis GO:0007599 9.46 GP1BB GP1BA
5 integrin-mediated signaling pathway GO:0007229 9.43 MYH9 ITGB3 ITGA2B
6 platelet formation GO:0030220 9.4 MYH9 ACTN1
7 blood coagulation, intrinsic pathway GO:0007597 9.37 GP1BB GP1BA
8 platelet activation GO:0030168 9.26 ITGB3 GP1BB GP1BA ACTN1
9 platelet aggregation GO:0070527 9.02 MYH9 ITGB3 ITGA2B GP1BA ACTN1

Molecular functions related to Autosomal Dominant Macrothrombocytopenia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.72 TPM4 MYH9 ITGB3 ITGA2B GP1BB
2 actin filament binding GO:0051015 9.43 TPM4 MYH9 ACTN1
3 extracellular matrix binding GO:0050840 9.16 ITGB3 ITGA2B
4 integrin binding GO:0005178 9.13 MYH9 ITGB3 ACTN1
5 fibrinogen binding GO:0070051 8.62 ITGB3 ITGA2B

Sources for Autosomal Dominant Macrothrombocytopenia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....