MCID: GRY002
MIFTS: 56

Gray Platelet Syndrome

Categories: Genetic diseases, Rare diseases, Blood diseases

Aliases & Classifications for Gray Platelet Syndrome

MalaCards integrated aliases for Gray Platelet Syndrome:

Name: Gray Platelet Syndrome 53 12 72 49 24 55 71 28 13 51 41 69
Platelet Alpha-Granule Deficiency 53 12 49 24 55 71 69
Gps 53 12 49 24 55 71
Bdplt4 53 12 24 71
Bleeding Disorder, Platelet-Type, 4 53 24
Grey Platelet Syndrome 24 71
Marked Decrease or Absence of Alpha-Granules and of Platelet-Specific Alpha-Granule Proteins 49
Bleeding Disorder, Platelet-Type, 4; Bdplt4 53
Platelet-Type Bleeding Disorder 4 12
Platelet Alpha Granule Deficiency 24
Bleeding Disorder Platelet-Type 4 71
Deficient Alpha Granule Syndrome 24
Alpha Storage Pool Deficiency 55
Platelet Granule Defect 24

Characteristics:

Orphanet epidemiological data:

55
gray platelet syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset of bleeding in infancy or early childhood


HPO:

31
gray platelet syndrome:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 53 139090
Disease Ontology 12 DOID:0111044
ICD10 32 D69.1
MeSH 41 D055652
Orphanet 55 ORPHA721
MESH via Orphanet 42 D055652
UMLS via Orphanet 70 C0272302 C2717750
ICD10 via Orphanet 33 D69.1
MedGen 39 C0272302

Summaries for Gray Platelet Syndrome

OMIM : 53 The gray platelet syndrome (GPS) is a rare inherited disorder characterized by mild to moderate bleeding tendency, moderate thrombocytopenia, and a marked decrease or absence of platelet alpha-granules and of the proteins contained in alpha-granules. The platelets are enlarged, but not giant, and have a gray appearance on light microscopy of Wright-stained peripheral blood smears due to decreased granules. Many patients with gray platelet syndrome develop a stable myelofibrosis (summary by Nurden and Nurden, 2007). Cases suggesting autosomal dominant and autosomal recessive inheritance have been described, indicating that GPS is probably a genetically heterogeneous disorder with more than one molecular cause. (139090)

MalaCards based summary : Gray Platelet Syndrome, also known as platelet alpha-granule deficiency, is related to glanzmann thrombasthenia and bernard-soulier syndrome, and has symptoms including splenomegaly, myelodysplasia and thrombocytopenia. An important gene associated with Gray Platelet Syndrome is NBEAL2 (Neurobeachin Like 2), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and NF-kappaB Signaling. Affiliated tissues include neutrophil, bone and bone marrow, and related phenotypes are hematopoietic system and cellular

UniProtKB/Swiss-Prot : 71 Gray platelet syndrome: A rare platelet disorder characterized by a selective deficiency in the number and contents of platelet alpha-granules. It is associated with mild to moderate bleeding tendency and moderate thrombocytopenia. The platelets are enlarged and have a gray appearance on light microscopy of Wright-stained peripheral blood smears due to decreased granules.

NIH Rare Diseases : 49 Gray plateletsyndrome (GPS) is a rare inherited bleeding disorder characterized by platelets that have a gray appearance, severe thrombocytopenia, myelofibrosis, and splenomegaly. About 60 cases from various populations around the world have been described in the literature to date. GPS results from the absence or reduction of alpha-granules in platelets, which store proteins that promote platelet adhesiveness and wound healing when secreted during an injury. GPS is caused by mutations in the NBEAL2 gene and inherited in an autosomal recessive manner.  Last updated: 10/3/2011

Genetics Home Reference : 24 Gray platelet syndrome is a bleeding disorder associated with abnormal platelets, which are blood cell fragments involved in blood clotting. People with this condition tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or extended bleeding following surgery, dental work, or minor trauma. Women with gray platelet syndrome often have irregular, heavy periods (menometrorrhagia). These bleeding problems are usually mild to moderate, but they have been life-threatening in a few affected individuals.

Disease Ontology : 12 An inherited blood coagulation disease characterized by selective deficiency in the number and contents of platelet alpha-granules, macrothrombocytopenia, enlarged platelets, myelofibrosis, splenomegaly, and increased bleeding time that has material basis in homozygous or compound heterozygous mutation in the NBEAL2 gene on chromosome 3p21.

Wikipedia : 72 Gray platelet syndrome (GPS), or platelet alpha-granule deficiency, is a rare congenital autosomal... more...

Related Diseases for Gray Platelet Syndrome

Diseases related to Gray Platelet Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 50)
# Related Disease Score Top Affiliating Genes
1 glanzmann thrombasthenia 32.3 GP9 SELP VWF
2 bernard-soulier syndrome 31.3 GP5 GP9 VWF
3 thrombocytopenia due to platelet alloimmunization 30.0 CD40LG SELP
4 thrombocytopenia 29.9 GATA1 GP9 MASTL
5 blood platelet disease 28.7 CD40LG GP5 GP9 SELP VWF
6 genitopatellar syndrome 11.8
7 bleeding disorder, platelet-type, 17 11.0
8 storage pool platelet disease 10.5 GFI1B NBEAL2
9 platelet aggregation, spontaneous 10.4 SELP VWF
10 von willebrand disease, type 1 10.4 GP6 VWF
11 heparin-induced thrombocytopenia 10.4 CD40LG SELP
12 stormorken syndrome 10.4 NBEAL2 SELP
13 cerebral arteritis 10.3 CD40LG VWF
14 monoclonal paraproteinemia 10.3 CD40LG VWF
15 thrombocytopenia-absent radius syndrome 10.3 GATA1 GFI1B NBEAL2
16 osteosclerotic myeloma 10.3 CD40LG VWF
17 korean hemorrhagic fever 10.3 CD40LG VWF
18 cervical adenosarcoma 10.3 GP5 GP6
19 cervix disease 10.3 CD40LG GP6
20 inverted follicular keratosis 10.2 GP5 GP6
21 coronary thrombosis 10.2 GP6 VWF
22 essential thrombocythemia 10.2 GATA1 SELP VWF
23 cervical carcinosarcoma 10.2 GP5 GP6
24 primary thrombocytopenia 10.2 CD40LG SELP VWF
25 cervix uteri carcinoma in situ 10.2 GP5 GP6
26 autoimmune disease of blood 10.2 CD40LG VWF
27 inherited blood coagulation disease 10.2 GP9 VWF
28 quebec platelet disorder 10.1 SELP SPARC
29 ehrlichiosis 10.0 CD40LG SELP
30 blood coagulation disease 10.0 CD40LG GP9 VWF
31 stroke, ischemic 10.0 GP6 SELP VWF
32 qualitative platelet defect 9.9 CD36 SELP VWF
33 legg-calve-perthes disease 9.9 CD40LG SELP
34 myelofibrosis 9.8
35 caffey disease 9.8 CD36 CD40LG
36 polykaryocytosis inducer 9.7
37 mccune-albright syndrome 9.7
38 thrombocytopenia 2 9.7
39 thrombocytopenia 1 9.7
40 autoimmune lymphoproliferative syndrome 9.7
41 myocardial infarction 9.7
42 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 9.7
43 acute myocardial infarction 9.7
44 hematopoietic stem cell transplantation 9.7
45 lymphoproliferative syndrome 9.7
46 adult-onset still's disease 9.7
47 meningitis 9.7
48 splenomegaly 9.7
49 endotheliitis 9.7
50 thrombasthenia 9.7 CD36 GP9 SELP

Graphical network of the top 20 diseases related to Gray Platelet Syndrome:



Diseases related to Gray Platelet Syndrome

Symptoms & Phenotypes for Gray Platelet Syndrome

Symptoms via clinical synopsis from OMIM:

53
Abdomen Spleen:
splenomegaly

Laboratory Abnormalities:
low-to-normal platelet count
median mean platelet volume 13fl
prolonged bleeding time (10 - >30 minutes)
normal platelet aggregation response to arachidonic acid (aa)
reduced platelet aggregation response to collagen and thrombin
more
Hematology:
thrombocytopenia
epistaxis
menorrhagia
myelofibrosis
easy bruisability
more

Clinical features from OMIM:

139090

Human phenotypes related to Gray Platelet Syndrome:

55 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 splenomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0001744
2 myelodysplasia 55 31 frequent (33%) Frequent (79-30%) HP:0002863
3 thrombocytopenia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001873
4 epistaxis 55 31 frequent (33%) Frequent (79-30%) HP:0000421
5 abnormality of the menstrual cycle 55 31 frequent (33%) Frequent (79-30%) HP:0000140
6 bruising susceptibility 55 31 hallmark (90%) Very frequent (99-80%) HP:0000978
7 abnormal bleeding 55 Very frequent (99-80%)
8 abnormality of thrombocytes 55 Very frequent (99-80%)
9 prolonged bleeding time 31 HP:0003010
10 menorrhagia 31 HP:0000132
11 myelofibrosis 31 HP:0011974
12 impaired collagen-induced platelet aggregation 31 HP:0008320
13 reduced von willebrand factor activity 31 HP:0008330
14 impaired thrombin-induced platelet aggregation 31 HP:0011872
15 reduced quantity of von willebrand factor 31 HP:0012147

MGI Mouse Phenotypes related to Gray Platelet Syndrome:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.13 GP9 MPIG6B NBEAL2 PLCG2 SELP SPARC
2 cellular MP:0005384 10.07 CD36 CD40LG GATA1 GFI1B MASTL MPIG6B
3 homeostasis/metabolism MP:0005376 10.07 SELP SPARC TREML1 VWF CD36 CD40LG
4 cardiovascular system MP:0005385 10.06 CD36 TREML1 VWF CD40LG CLDN5 GATA1
5 immune system MP:0005387 9.93 CD36 CD40LG GATA1 GFI1B GP6 MPIG6B
6 integument MP:0010771 9.56 CD40LG GATA1 GFI1B GP6 PLCG2 SELP
7 skeleton MP:0005390 9.28 CD36 CD40LG GATA1 MPIG6B NBEAL2 PLCG2

Drugs & Therapeutics for Gray Platelet Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Genetic Analysis of Gray Platelet Syndrome Completed NCT00069680
2 Study of Megakaryocytes From Patients With Abnormal Platelet Vesicles Completed NCT00086476

Search NIH Clinical Center for Gray Platelet Syndrome

Cochrane evidence based reviews: gray platelet syndrome

Genetic Tests for Gray Platelet Syndrome

Genetic tests related to Gray Platelet Syndrome:

# Genetic test Affiliating Genes
1 Gray Platelet Syndrome 28 NBEAL2

Anatomical Context for Gray Platelet Syndrome

MalaCards organs/tissues related to Gray Platelet Syndrome:

38
Neutrophil, Bone, Bone Marrow, Endothelial

Publications for Gray Platelet Syndrome

Articles related to Gray Platelet Syndrome:

(show top 50) (show all 67)
# Title Authors Year
1
Gray platelet syndrome: Novel mutations of the NBEAL2 gene. ( 27870194 )
2017
2
A case of adult-onset Still's disease accompanied by pseudo-gray platelet syndrome. ( 29043244 )
2017
3
A novel nonsense NBEAL2 gene mutation causing severe bleeding in a patient with gray platelet syndrome. ( 28504079 )
2017
4
Should any Genetic Defect Affecting I+-Granules in Platelets be Classified as Gray Platelet Syndrome? ( 26971401 )
2016
5
Spontaneous 8bp Deletion in Nbeal2 Recapitulates the Gray Platelet Syndrome in Mice. ( 26950939 )
2016
6
Corrigendum: Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients. ( 27126656 )
2016
7
Onyx embolization of an intraosseous pseudoaneurysm of the middle meningeal artery in a patient with meningiomatosis, McCune-Albright syndrome, and gray platelet syndrome. ( 26588455 )
2016
8
Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients. ( 26987485 )
2016
9
Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome. ( 25806575 )
2015
10
A Dominant-Negative GFI1B Mutation in the Gray Platelet Syndrome. ( 26287868 )
2015
11
Gray platelet syndrome can mimic autoimmune lymphoproliferative syndrome. ( 26472737 )
2015
12
Pseudo gray platelet syndrome: the first case report in Korea. ( 26157784 )
2015
13
GFI1B Mutation Causes Autosomal Dominant Gray Platelet Syndrome. ( 24635673 )
2014
14
Gray Platelet Syndrome: Pro-inflammatory megakaryocytes and I+-granule loss cause myelofibrosis and confer resistance to cancer metastasis in mice. ( 25258341 )
2014
15
A dominant-negative GFI1B mutation in the gray platelet syndrome. ( 24325358 )
2014
16
A case of gray platelet syndrome masked by immune thrombocytopenia at presentation. ( 24577417 )
2014
17
Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice. ( 23863626 )
2013
18
Gray platelet syndrome. ( 23427340 )
2013
19
The Nbeal2(-/-) mouse as a model for the gray platelet syndrome. ( 25003009 )
2013
20
Successful hematopoietic engraftment with gray platelets after allogeneic hematopoietic stem cell transplantation from gray platelet syndrome donor. ( 23358204 )
2013
21
Gray platelet syndrome: macrothrombocytopenia with deficient I+-granules. ( 23193541 )
2012
22
Thrombocytopenias due to gray platelet syndrome or THC2 mutations. ( 22102272 )
2011
23
NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet alpha-granules. ( 21765412 )
2011
24
Successful pregnancy and delivery in a woman with gray platelet syndrome. ( 21443042 )
2011
25
Expanding perfusion across disciplines: the use of thrombelastography technology to reduce risk in an obstetrics patient with Gray Platelet Syndrome--a case study. ( 21227981 )
2011
26
Gray platelet syndrome. ( 21800352 )
2011
27
Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. ( 21765411 )
2011
28
Homozygosity mapping with SNP arrays confirms 3p21 as a recessive locus for gray platelet syndrome and narrows the interval significantly. ( 21263149 )
2011
29
Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. ( 21765413 )
2011
30
The I+-granule proteome: novel proteins in normal and ghost granules in gray platelet syndrome. ( 20524979 )
2010
31
Gray platelet syndrome: natural history of a large patient cohort and locus assignment to chromosome 3p. ( 20709904 )
2010
32
Phenotypic heterogeneity in the Gray platelet syndrome extends to the expression of TREM family member, TLT-1. ( 18612537 )
2008
33
X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation. ( 17209061 )
2007
34
Defective platelet responsiveness to thrombin and protease-activated receptors agonists in a novel case of gray platelet syndrome: correlation between the platelet defect and the alpha-granule content in the patient and four relatives. ( 17137471 )
2007
35
The gray platelet syndrome: clinical spectrum of the disease. ( 16442192 )
2007
36
Gray Platelet Syndrome in a Somalian family. ( 17127480 )
2006
37
Neutrophil secretory defect in the gray platelet syndrome: a new case. ( 16308182 )
2006
38
Molecular study of the hematopoietic zinc finger gene in three unrelated families with gray platelet syndrome. ( 16102114 )
2005
39
Neutrophils in the gray platelet syndrome. ( 15370105 )
2004
40
Severe deficiency of glycoprotein VI in a patient with gray platelet syndrome. ( 15010364 )
2004
41
Gray platelet syndrome presenting as menorrhagia. ( 12627861 )
2003
42
Pseudo gray platelet syndrome in a patient with acute myocardial infarction. ( 12463604 )
2002
43
Newly recognized cellular abnormalities in the gray platelet syndrome. ( 11520786 )
2001
44
A new genetic isolate of gray platelet syndrome (GPS): clinical, cellular, and hematologic characteristics. ( 11708859 )
2001
45
The magic of immersion oil: gray platelet syndrome. ( 9658735 )
1998
46
Platelet alpha granule deficiency associated with decreased P-selectin and selective impairment of thrombin-induced activation in a new patient with gray platelet syndrome (alpha-storage pool deficiency). ( 9042822 )
1997
47
Gray platelet syndrome with splenomegaly and signs of extramedullary hematopoiesis: a case report with review of the literature. ( 8192152 )
1994
48
Gray platelet syndrome. Dissociation between abnormal sorting in megakaryocyte alpha-granules and normal sorting in Weibel-Palade bodies of endothelial cells. ( 7504696 )
1993
49
Platelets of the Wistar Furth rat have reduced levels of alpha-granule proteins. An animal model resembling gray platelet syndrome. ( 2040691 )
1991
50
Gray platelet syndrome: relationship between morphological abnormality of the dense tubular system (DTS) and intracellular Ca++ mobilization in the platelet. ( 2629468 )
1989

Variations for Gray Platelet Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Gray Platelet Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 NBEAL2 p.Leu388Pro VAR_066976 rs387907113
2 NBEAL2 p.Glu643Val VAR_066977 rs387907114
3 NBEAL2 p.Trp677Arg VAR_066978
4 NBEAL2 p.Glu1833Lys VAR_066980
5 NBEAL2 p.Arg1839Cys VAR_066981 rs750160418
6 NBEAL2 p.Pro2100Leu VAR_066982 rs387907115
7 NBEAL2 p.His2263Tyr VAR_066983
8 NBEAL2 p.Ser2269Leu VAR_066984 rs749896920

ClinVar genetic disease variations for Gray Platelet Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 NBEAL2 NM_015175.2(NBEAL2): c.2701C> T (p.Arg901Ter) single nucleotide variant Pathogenic rs387907112 GRCh37 Chromosome 3, 47038800: 47038800
2 NBEAL2 NM_015175.2(NBEAL2): c.881C> G (p.Ser294Ter) single nucleotide variant Pathogenic rs372277612 GRCh37 Chromosome 3, 47033134: 47033134
3 NBEAL2 NM_015175.2(NBEAL2): c.1163T> C (p.Leu388Pro) single nucleotide variant Pathogenic rs387907113 GRCh37 Chromosome 3, 47035476: 47035476
4 NBEAL2 NM_015175.2(NBEAL2): c.1928A> T (p.Glu643Val) single nucleotide variant Pathogenic rs387907114 GRCh37 Chromosome 3, 47037233: 47037233
5 NBEAL2 NM_015175.2(NBEAL2): c.6299C> T (p.Pro2100Leu) single nucleotide variant Pathogenic rs387907115 GRCh37 Chromosome 3, 47046466: 47046466
6 NBEAL2 NM_015175.2(NBEAL2): c.1823G> A (p.Trp608Ter) single nucleotide variant Pathogenic rs794726682 GRCh38 Chromosome 3, 46995558: 46995558
7 NBEAL2 NM_015175.2(NBEAL2): c.5413dupG (p.Ala1805Glyfs) duplication Pathogenic rs794726683 GRCh37 Chromosome 3, 47044246: 47044246
8 NBEAL2 NM_015175.2(NBEAL2): c.1793G> A (p.Trp598Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 3, 47037018: 47037018
9 NBEAL2 NM_015175.2(NBEAL2): c.4081G> T (p.Glu1361Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 3, 47041670: 47041670

Expression for Gray Platelet Syndrome

Search GEO for disease gene expression data for Gray Platelet Syndrome.

Pathways for Gray Platelet Syndrome

Pathways related to Gray Platelet Syndrome according to GeneCards Suite gene sharing:

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.93 CD36 GATA1 GP5 GP6 GP9 MPIG6B
2 12.31 CD40LG GATA1 GFI1B PLCG2
3
Show member pathways
11.91 GP5 GP6 GP9 VWF
4
Show member pathways
11.9 CD36 GP5 GP6 GP9 VWF
5
Show member pathways
11.88 GP6 MPIG6B PLCG2
6 11.85 CD40LG CLDN5 SELP
7 11.74 GP5 GP6 GP9 PLCG2 VWF
8
Show member pathways
11.64 GP5 GP9 VWF
9 11.62 CD36 GP5 GP9
10 11.3 CD36 CD40LG SELP
11 11.04 CD36 CD40LG
12 10.81 CD36 GP5 GP6 GP9 PLCG2 VWF
13 10.54 GP5 GP9 VWF
14 10.37 GP5 GP6 GP9 VWF

GO Terms for Gray Platelet Syndrome

Cellular components related to Gray Platelet Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.73 CD36 CD40LG GP5 GP6 GP9 SELP
2 plasma membrane GO:0005886 9.73 CD36 CD40LG CLDN5 GP5 GP6 GP9
3 platelet alpha granule GO:0031091 9.16 SPARC VWF
4 platelet alpha granule membrane GO:0031092 8.8 CD36 SELP SPARC

Biological processes related to Gray Platelet Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.83 CD36 GP5 GP9 SELP VWF
2 platelet degranulation GO:0002576 9.67 CD36 SELP SPARC VWF
3 platelet formation GO:0030220 9.5 GATA1 MPIG6B NBEAL2
4 blood coagulation GO:0007596 9.5 CD36 GATA1 GP5 GP6 GP9 MPIG6B
5 leukocyte cell-cell adhesion GO:0007159 9.48 CD40LG SELP
6 positive regulation of interleukin-12 production GO:0032735 9.46 CD36 CD40LG
7 hemostasis GO:0007599 9.46 GP5 GP6 GP9 VWF
8 blood coagulation, intrinsic pathway GO:0007597 9.43 GP5 GP9 VWF
9 megakaryocyte differentiation GO:0030219 9.4 GATA1 MPIG6B
10 platelet activation GO:0030168 9.17 CD40LG GP5 GP6 GP9 MPIG6B PLCG2

Molecular functions related to Gray Platelet Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen binding GO:0005518 8.8 GP6 SPARC VWF

Sources for Gray Platelet Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
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47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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