Details of Disease

General Information of Disease (ID: DISLOTCW)

• Disease Name: Gray platelet syndrome
• Synonyms: marked decrease or absence of alpha-granules and of platelet-specific alpha-granule proteins; bleeding disorder, Platelet-type, 4; platelet alpha-granule deficiency; Alpha storage pool deficiency; BDPLT4; platelet-type bleeding disorder 4; GPS; gray platelet syndrome
• Definition: Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by macrothrombocytopenia, myelofibrosis, splenomegaly and typical gray appearance of platelets on Wright stained peripheral blood smear.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISIUNXT: Inherited bleeding disorder, platelet-type
  DIS76YK5: Alpha granule disease
  DISLOTCW: Gray platelet syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0007686
  MESH ID: D055652
  UMLS CUI: C0272302
  OMIM ID: 139090
  MedGen ID: 82900
  Orphanet ID: 721
  SNOMED CT ID: 51720005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GP6	TTTJUVZ	Strong	Biomarker	[1]
KAT6B	TTH4VJL	Strong	Genetic Variation	[2]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GFI1B	OTRDW8YO	moderate	Biomarker	[3]
ANKRD26	OT2ENKKV	Strong	Genetic Variation	[4]
DOCK7	OTINNVQV	Strong	Biomarker	[5]
GPS1	OT97FRYE	Strong	Biomarker	[6]
GPS2	OT065FSS	Strong	Biomarker	[6]
JTB	OT314JB6	Strong	Biomarker	[7]
LMX1B	OTM8145D	Strong	Biomarker	[8]
MASTL	OTQ7YKK5	Strong	Genetic Variation	[4]
NBEAL1	OTLJ11N3	Strong	Genetic Variation	[5]
RABGGTA	OTYMG99C	Strong	Genetic Variation	[9]
NBEAL2	OTMCAXWR	Definitive	Autosomal recessive	[10]

References

• [1] Severe deficiency of glycoprotein VI in a patient with gray platelet syndrome.Blood. 2004 Jul 1;104(1):107-14. doi: 10.1182/blood-2003-11-3842. Epub 2004 Mar 9.
• [2] A novel truncating variant within exon 7 of KAT6B associated with features of both Say-Barber-Bieseker-Young-Simpson syndrome and genitopatellar syndrome: Further evidence of a continuum in the clinical spectrum of KAT6B-related disorders.Am J Med Genet A. 2018 Feb;176(2):455-459. doi: 10.1002/ajmg.a.38571. Epub 2017 Dec 11.
• [3] A dominant-negative GFI1B mutation in the gray platelet syndrome.N Engl J Med. 2014 Jan 16;370(3):245-53. doi: 10.1056/NEJMoa1308130. Epub 2013 Dec 10.
• [4] Thrombocytopenias due to gray platelet syndrome or THC2 mutations.Semin Thromb Hemost. 2011 Sep;37(6):690-7. doi: 10.1055/s-0031-1291379. Epub 2011 Nov 18.
• [5] Nbeal2 interacts with Dock7, Sec16a, and Vac14.Blood. 2018 Mar 1;131(9):1000-1011. doi: 10.1182/blood-2017-08-800359. Epub 2017 Nov 29.
• [6] Glasgow prognostic score predicts therapeutic outcome after hepatic resection for hepatocellular carcinoma.Oncol Lett. 2017 Jul;14(1):293-298. doi: 10.3892/ol.2017.6104. Epub 2017 Apr 28.
• [7] 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.J Thromb Haemost. 2007 Mar;5(3):551-9. doi: 10.1111/j.1538-7836.2007.02329.x. Epub 2006 Nov 28.
• [8] Ovotestes and XY sex reversal in a female with an interstitial 9q33.3-q34.1 deletion encompassing NR5A1 and LMX1B causing features of Genitopatellar syndrome.Am J Med Genet A. 2007 May 15;143A(10):1071-81. doi: 10.1002/ajmg.a.31685.
• [9] 5'-UTR structural organization, transcript expression, and mutational analysis of the human Rab geranylgeranyl transferase alpha-subunit (RABGGTA) gene.Mol Genet Metab. 2000 Dec;71(4):599-608. doi: 10.1006/mgme.2000.3091.
• [10] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.