Details of Disease

General Information of Disease (ID: DISIUNXT)

• Disease Name: Inherited bleeding disorder, platelet-type
• Synonyms: thrombocytopathy; platelet disorder; blood platelet disease; bleeding disorder, platelet-type
• Disease Hierarchy:
  DIS27CUA: Bleeding disorder
  DISOOSU2: Blood platelet disease
  DISYKSRF: Genetic disease
  DISIUNXT: Inherited bleeding disorder, platelet-type
• Disease Identifiers:
  MONDO ID: MONDO_0000009
  MESH ID: D001791
  UMLS CUI: C0005818
  MedGen ID: 610
  Orphanet ID: 248326
  SNOMED CT ID: 22716005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TBXA2R	TT2O84V	Disputed	Biomarker	[1]
ABCG5	TTKZ7WY	Strong	Biomarker	[2]
CD36	TTPJMCU	Strong	CausalMutation	[3]
RUNX1	TTWIN3H	Strong	Genetic Variation	[4]
SRC	TT6PKBN	Strong	Biomarker	[5]
WAS	TTE8T73	Strong	Genetic Variation	[6]
PLA2G4A	TTT1JVS	Definitive	Biomarker	[7]

This Disease Is Related to 22 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GP9	OTA19OKO	Limited	Biomarker	[8]
MYH9	OT94Z706	moderate	Biomarker	[9]
RASGRP1	OTX9WN2E	moderate	Biomarker	[10]
RASGRP2	OTABVLVQ	moderate	Biomarker	[10]
TPM4	OTN4YLYR	moderate	Biomarker	[11]
ABCG8	OTIJ76XW	Strong	Biomarker	[12]
ACTB	OT1MCP2F	Strong	Biomarker	[13]
AP3D1	OTJLI0IM	Strong	Biomarker	[14]
APCDD1	OTV9AD0L	Strong	Biomarker	[15]
ARPC1B	OTYE3DN2	Strong	Biomarker	[16]
CDC42	OT5QBC5M	Strong	Biomarker	[17]
CYCS	OTBFALJD	Strong	Biomarker	[18]
FERMT3	OTFQOT3C	Strong	Biomarker	[19]
FYB1	OT6345CH	Strong	Genetic Variation	[20]
GATA1	OTX1R7O1	Strong	Genetic Variation	[21]
GP1BB	OTD7XNLL	Strong	Genetic Variation	[22]
KDSR	OTCIES3H	Strong	Biomarker	[23]
MPIG6B	OTVNKQWA	Strong	Biomarker	[24]
PRKACG	OTKOQYF8	Strong	Genetic Variation	[10]
SLFN14	OTMB4Y3R	Strong	Biomarker	[25]
SPRR2A	OT62ZU6B	Strong	Genetic Variation	[26]
MYH10	OTXN2WXS	Definitive	Biomarker	[27]

References

• [1] A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis. Blood. 2010 Jan 14;115(2):363-9. doi: 10.1182/blood-2009-08-236976. Epub 2009 Oct 14.
• [2] Congenital macrothrombocytopenia is a heterogeneous disorder in India.Haemophilia. 2016 Jul;22(4):570-82. doi: 10.1111/hae.12917. Epub 2016 Jun 13.
• [3] Diverse CD36 expression among Japanese population: defective CD36 mutations cause platelet and monocyte CD36 reductions in not only deficient but also normal phenotype subjects.Thromb Res. 2015 May;135(5):951-7. doi: 10.1016/j.thromres.2015.03.002. Epub 2015 Mar 8.
• [4] ClinGen Myeloid Malignancy Variant Curation Expert Panel recommendations for germline RUNX1 variants.Blood Adv. 2019 Oct 22;3(20):2962-2979. doi: 10.1182/bloodadvances.2019000644.
• [5] A dominant gain-of-function mutation in universal tyrosine kinase SRC causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies. Sci Transl Med. 2016 Mar 2;8(328):328ra30. doi: 10.1126/scitranslmed.aad7666. Epub 2016 Mar 2.
• [6] Analyses of Genetic and Clinical Parameters for Screening Patients With Inherited Thrombocytopenia with Small or Normal-Sized Platelets. Pediatr Blood Cancer. 2015 Dec;62(12):2082-8. doi: 10.1002/pbc.25668. Epub 2015 Jul 14.
• [7] Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction. J Clin Invest. 2008 Jun;118(6):2121-31. doi: 10.1172/JCI30473.
• [8] A large deletion in the GP9 gene in Cocker Spaniel dogs with Bernard-Soulier syndrome.PLoS One. 2019 Sep 4;14(9):e0220625. doi: 10.1371/journal.pone.0220625. eCollection 2019.
• [9] Thrombin generation in two families with MYH9-related platelet disorder.Platelets. 2016;27(3):264-7. doi: 10.3109/09537104.2015.1064882. Epub 2015 Aug 6.
• [10] Update on the inherited platelet disorders.Curr Opin Hematol. 2015 Sep;22(5):460-6. doi: 10.1097/MOH.0000000000000171.
• [11] Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia. J Clin Invest. 2017 Mar 1;127(3):814-829. doi: 10.1172/JCI86154. Epub 2017 Jan 30.
• [12] Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia.J Thromb Haemost. 2017 Sep;15(9):1859-1866. doi: 10.1111/jth.13777. Epub 2017 Aug 5.
• [13] Twinfilin 2a regulates platelet reactivity and turnover in mice.Blood. 2017 Oct 12;130(15):1746-1756. doi: 10.1182/blood-2017-02-770768. Epub 2017 Jul 25.
• [14] A new type of syndromic albinism associated with mutations in AP3D1.Pigment Cell Melanoma Res. 2017 Jan;30(1):5-7. doi: 10.1111/pcmr.12543. Epub 2016 Nov 30.
• [15] Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.
• [16] Combined immunodeficiency with severe inflammation and allergy caused by ARPC1B deficiency. J Allergy Clin Immunol. 2017 Jul;140(1):273-277.e10. doi: 10.1016/j.jaci.2016.09.061. Epub 2016 Dec 10.
• [17] Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.Am J Hum Genet. 2018 Feb 1;102(2):309-320. doi: 10.1016/j.ajhg.2017.12.015. Epub 2018 Jan 25.
• [18] Platelets from a patient heterozygous for the defect of P2CYC receptors for ADP have a secretion defect despite normal thromboxane A2 production and normal granule stores: further evidence that some cases of platelet 'primary secretion defect' are heterozygous for a defect of P2CYC receptors.Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):E101-6. doi: 10.1161/01.atv.20.11.e101.
• [19] Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med. 2008 Mar;14(3):325-30. doi: 10.1038/nm1722. Epub 2008 Feb 17.
• [20] ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia.Blood. 2018 Aug 9;132(6):635-646. doi: 10.1182/blood-2018-01-829259. Epub 2018 Jun 27.
• [21] Analysis of disease-causing GATA1 mutations in murine gene complementation systems. Blood. 2013 Jun 27;121(26):5218-27. doi: 10.1182/blood-2013-03-488080. Epub 2013 May 23.
• [22] Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia. Blood. 2017 Jan 26;129(4):520-524. doi: 10.1182/blood-2016-08-732248. Epub 2016 Nov 14.
• [23] Mutations in KDSR Cause Recessive Progressive Symmetric Erythrokeratoderma. Am J Hum Genet. 2017 Jun 1;100(6):978-984. doi: 10.1016/j.ajhg.2017.05.003.
• [24] Mice lacking the ITIM-containing receptor G6b-B exhibit macrothrombocytopenia and aberrant platelet function.Sci Signal. 2012 Oct 30;5(248):ra78. doi: 10.1126/scisignal.2002936.
• [25] SLFN14-related thrombocytopenia: identification within a large series of patients with inherited thrombocytopenia.Thromb Haemost. 2016 May 2;115(5):1076-9. doi: 10.1160/TH15-11-0884. Epub 2016 Jan 14.
• [26] Inherited bleeding disorders in older women.Maturitas. 2012 May;72(1):35-41. doi: 10.1016/j.maturitas.2012.02.008. Epub 2012 Mar 22.
• [27] MYH10 protein expression in platelets as a biomarker of RUNX1 and FLI1 alterations.Blood. 2012 Sep 27;120(13):2719-22. doi: 10.1182/blood-2012-04-422352. Epub 2012 Jun 7.