MCID: GRY002
MIFTS: 53

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 54 12 50 24 25 56 71 29 13 52 42 69
Platelet Alpha-Granule Deficiency 12 50 24 25 56 71 69
Gps 12 50 25 56 71
Bdplt4 12 24 25 71
Platelet-Type Bleeding Disorder 4 12 24
Grey Platelet Syndrome 25 71
Marked Decrease or Absence of Alpha-Granules and of Platelet-Specific Alpha-Granule Proteins 50
Bleeding Disorder, Platelet-Type, 4 25
Platelet Alpha Granule Deficiency 25
Bleeding Disorder Platelet-Type 4 71
Deficient Alpha Granule Syndrome 25
Alpha Storage Pool Deficiency 56
Platelet Granule Defect 25

Characteristics:

Orphanet epidemiological data:

56
gray platelet syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

54
Inheritance:
autosomal recessive

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


HPO:

32
gray platelet syndrome:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 54 139090
Disease Ontology 12 DOID:0111044
ICD10 33 D69.1
MeSH 42 D055652
Orphanet 56 ORPHA721
MESH via Orphanet 43 D055652
UMLS via Orphanet 70 C0272302 C2717750
ICD10 via Orphanet 34 D69.1
MedGen 40 C0272302
UMLS 69 C0272302

Summaries for Gray Platelet Syndrome

OMIM : 54
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 genitopatellar syndrome and glanzmann thrombasthenia, and has symptoms including splenomegaly, thrombocytopenia and epistaxis. 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

NIH Rare Diseases : 50 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

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.

Genetics Home Reference : 25 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 top 50) (show all 58)
id Related Disease Score Top Affiliating Genes
1 genitopatellar syndrome 11.6
2 glanzmann thrombasthenia 11.2
3 bleeding disorder, platelet-type, 11 11.1
4 bernard-soulier syndrome, type c 10.9
5 von willebrand disease, platelet-type 10.9
6 bleeding disorder, platelet-type, 17 10.9
7 glycoprotein ia deficiency 10.8
8 gastroparesis 10.8
9 goodpasture syndrome 10.8
10 cystic angiomatosis of bone, diffuse 10.7 GFI1B NBEAL2
11 ube2t-related fanconi anemia 10.7 SELP VWF
12 hereditary amyloidosis 10.6 CD40LG SELP
13 segawa syndrome, recessive 10.6 NBEAL2 SELP
14 colonic benign neoplasm 10.5 CD40LG VWF
15 von willibrand disease, type 3 10.5 GP6 VWF
16 thrombocytopenia-absent radius syndrome 10.5 GATA1 GFI1B NBEAL2
17 indolent myeloma 10.5 CD40LG VWF
18 lujo hemorrhagic fever 10.5 CD40LG VWF
19 retromolar area cancer 10.3 CD40LG SELP VWF
20 thumb stiff brachydactyly mental retardation 10.3 SELP VWF
21 basilar artery insufficiency 10.3 GATA1 SELP VWF
22 essential thrombocythemia 10.3 GP9 VWF
23 uterine body mixed cancer 10.3 GP5 GP6
24 autonomic peripheral neuropathy 10.3 CD40LG VWF
25 telangiectatic osteogenic sarcoma 10.3 GP5 GP6
26 ovarian mesodermal adenosarcoma 10.2 GP5 GP6
27 larynx carcinoma in situ 10.2 GP5 GP6
28 retinal dystrophy, iris coloboma, and comedogenic acne syndrome 10.2 SELP SPARC
29 bleeding disorder, platelet-type, 16, autosomal dominant 10.2 GP9 SELP VWF
30 tuberculoid leprosy 10.1 CD40LG SELP
31 mental depression 10.1 CD40LG GP9 SELP
32 leukemia 10.1
33 stroke, ischemic 10.1 GP6 SELP VWF
34 ocular hyperemia 10.1 CD40LG GP9 VWF
35 tracheal cancer 10.0 GATA1 GP9 MASTL
36 thrombasthenia 10.0
37 hiv-1 9.9
38 thrombocytopenia 9.9
39 lymphoma 9.9
40 breast cancer 9.9
41 acute leukemia 9.8
42 mental retardation, autosomal recessive 35 9.8 CD36 CD40LG
43 hepatocellular carcinoma 9.7
44 adenocarcinoma 9.7
45 immunodeficiency 21 9.7 GP5 GP9 NBEAL2 VWF
46 physical urticaria 9.7 CD36 CD40LG
47 hematopoietic stem cell transplantation 9.6
48 myocardial infarction 9.6
49 lymphoproliferative syndrome 9.6
50 autoimmune lymphoproliferative syndrome 9.6

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:

54

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
easy bruisability
mild to moderate bleeding tendencies
menorrhagia
more

Clinical features from OMIM:

139090

Human phenotypes related to Gray Platelet Syndrome:

32 (show all 11)
id Description HPO Frequency HPO Source Accession
1 splenomegaly 32 HP:0001744
2 thrombocytopenia 32 HP:0001873
3 epistaxis 32 HP:0000421
4 menorrhagia 32 HP:0000132
5 myelofibrosis 32 HP:0011974
6 prolonged bleeding time 32 HP:0003010
7 bruising susceptibility 32 HP:0000978
8 impaired collagen-induced platelet aggregation 32 HP:0008320
9 reduced von willebrand factor activity 32 HP:0008330
10 impaired thrombin-induced platelet aggregation 32 HP:0011872
11 reduced quantity of von willebrand factor 32 HP:0012147

MGI Mouse Phenotypes related to Gray Platelet Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.13 PLCG2 SELP SPARC TREML1 VWF CD36
2 cellular MP:0005384 10.07 CD40LG GATA1 GFI1B MASTL MPIG6B NBEAL2
3 homeostasis/metabolism MP:0005376 10.07 VWF CD36 CD40LG GATA1 GFI1B GP5
4 cardiovascular system MP:0005385 10.06 CD36 CD40LG CLDN5 GATA1 GFI1B PLCG2
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:


id 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:

id Genetic test Affiliating Genes
1 Gray Platelet Syndrome 29 24 NBEAL2

Anatomical Context for Gray Platelet Syndrome

MalaCards organs/tissues related to Gray Platelet Syndrome:

39
Neutrophil, Bone, Bone Marrow, Endothelial

Publications for Gray Platelet Syndrome

Articles related to Gray Platelet Syndrome:

(show top 50) (show all 66)
id Title Authors Year
1
Gray platelet syndrome: Novel mutations of the NBEAL2 gene. ( 27870194 )
2017
2
A novel nonsense NBEAL2 gene mutation causing severe bleeding in a patient with gray platelet syndrome. ( 28504079 )
2017
3
Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients. ( 26987485 )
2016
4
Spontaneous 8bp Deletion in Nbeal2 Recapitulates the Gray Platelet Syndrome in Mice. ( 26950939 )
2016
5
Corrigendum: Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients. ( 27126656 )
2016
6
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
7
Should any Genetic Defect Affecting I+-Granules in Platelets be Classified as Gray Platelet Syndrome? ( 26971401 )
2016
8
Pseudo gray platelet syndrome: the first case report in Korea. ( 26157784 )
2015
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
Gray Platelet Syndrome: Pro-inflammatory megakaryocytes and I+-granule loss cause myelofibrosis and confer resistance to cancer metastasis in mice. ( 25258341 )
2014
13
GFI1B Mutation Causes Autosomal Dominant Gray Platelet Syndrome. ( 24635673 )
2014
14
A case of gray platelet syndrome masked by immune thrombocytopenia at presentation. ( 24577417 )
2014
15
A dominant-negative GFI1B mutation in the gray platelet syndrome. ( 24325358 )
2014
16
The Nbeal2(-/-) mouse as a model for the gray platelet syndrome. ( 25003009 )
2013
17
Gray platelet syndrome. ( 23427340 )
2013
18
Successful hematopoietic engraftment with gray platelets after allogeneic hematopoietic stem cell transplantation from gray platelet syndrome donor. ( 23358204 )
2013
19
Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice. ( 23863626 )
2013
20
Gray platelet syndrome: macrothrombocytopenia with deficient I+-granules. ( 23193541 )
2012
21
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
22
NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet alpha-granules. ( 21765412 )
2011
23
Gray platelet syndrome. ( 21800352 )
2011
24
Thrombocytopenias due to gray platelet syndrome or THC2 mutations. ( 22102272 )
2011
25
Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. ( 21765411 )
2011
26
Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. ( 21765413 )
2011
27
Homozygosity mapping with SNP arrays confirms 3p21 as a recessive locus for gray platelet syndrome and narrows the interval significantly. ( 21263149 )
2011
28
Successful pregnancy and delivery in a woman with gray platelet syndrome. ( 21443042 )
2011
29
The I+-granule proteome: novel proteins in normal and ghost granules in gray platelet syndrome. ( 20524979 )
2010
30
Gray platelet syndrome: natural history of a large patient cohort and locus assignment to chromosome 3p. ( 20709904 )
2010
31
Phenotypic heterogeneity in the Gray platelet syndrome extends to the expression of TREM family member, TLT-1. ( 18612537 )
2008
32
The gray platelet syndrome: clinical spectrum of the disease. ( 16442192 )
2007
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
Gray Platelet Syndrome in a Somalian family. ( 17127480 )
2006
36
Neutrophil secretory defect in the gray platelet syndrome: a new case. ( 16308182 )
2006
37
Molecular study of the hematopoietic zinc finger gene in three unrelated families with gray platelet syndrome. ( 16102114 )
2005
38
Neutrophils in the gray platelet syndrome. ( 15370105 )
2004
39
Severe deficiency of glycoprotein VI in a patient with gray platelet syndrome. ( 15010364 )
2004
40
Gray platelet syndrome presenting as menorrhagia. ( 12627861 )
2003
41
Pseudo gray platelet syndrome in a patient with acute myocardial infarction. ( 12463604 )
2002
42
A new genetic isolate of gray platelet syndrome (GPS): clinical, cellular, and hematologic characteristics. ( 11708859 )
2001
43
Newly recognized cellular abnormalities in the gray platelet syndrome. ( 11520786 )
2001
44
The magic of immersion oil: gray platelet syndrome. ( 9658735 )
1998
45
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
46
Gray platelet syndrome with splenomegaly and signs of extramedullary hematopoiesis: a case report with review of the literature. ( 8192152 )
1994
47
Gray platelet syndrome. Dissociation between abnormal sorting in megakaryocyte alpha-granules and normal sorting in Weibel-Palade bodies of endothelial cells. ( 7504696 )
1993
48
Platelets of the Wistar Furth rat have reduced levels of alpha-granule proteins. An animal model resembling gray platelet syndrome. ( 2040691 )
1991
49
Gray platelet syndrome: relationship between morphological abnormality of the dense tubular system (DTS) and intracellular Ca++ mobilization in the platelet. ( 2629468 )
1989
50
Gray platelet syndrome. ( 2763381 )
1989

Variations for Gray Platelet Syndrome

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

71
id 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
id 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 GRCh38 Chromosome 3, 47000180: 47000180

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)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.93 CD36 GATA1 GP5 GP6 GP9 MPIG6B
2 12.29 CD40LG GATA1 GFI1B PLCG2
3
Show member pathways
11.94 CD36 GP5 GP6 GP9 VWF
4
Show member pathways
11.91 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 11.08 CD36 CD40LG
12 10.81 CD36 GP5 GP6 GP9 PLCG2 VWF
13 10.5 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:

id 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:

id 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:

id 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
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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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