Details of Disease | DrugMAP

General Information of Disease (ID: DISUTMSW)

Disease Name	Autosomal dominant macrothrombocytopenia
Definition	This syndrome is characterized by congenital thrombocytopenia associated with the presence of large platelets.
Disease Hierarchy	DISANU9Q: Inherited thrombocytopenia DISUTMSW: Autosomal dominant macrothrombocytopenia
Disease Identifiers	MONDO ID MONDO_0015372 UMLS CUI C4304021 MedGen ID 929690 Orphanet ID 140957 SNOMED CT ID 720521008

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TUBA4A	OTWDBVZ4	Limited	Autosomal dominant	[1]
TUBB1	OTEVMMYH	Supportive	Autosomal dominant	[2]
ACTN1	OTUCLNXH	Supportive	Autosomal dominant	[7]
GFI1B	OTRDW8YO	Supportive	Autosomal dominant	[8]
GP1BA	OT62PSOB	Supportive	Autosomal dominant	[3]
GP1BB	OTD7XNLL	Supportive	Autosomal dominant	[9]
ITGA2B	OT4Y17PY	Supportive	Autosomal dominant	[10]
ITGB3	OTWCK1K6	Supportive	Autosomal dominant	[4]
TPM4	OTN4YLYR	Supportive	Autosomal dominant	[11]
TRPM7	OTHG1J2G	Supportive	Autosomal dominant	[5]
MYH9	OT94Z706	Strong	Genetic Variation	[12]
------------------------------------------------------------------------------------


⏷ Show the Full List of 11 DOT(s)

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GP1BA	TTVB0Q9	Supportive	Autosomal dominant	[3]
ITGB3	TTJA1ZO	Supportive	Autosomal dominant	[4]
TRPM7	TTFPVZO	Supportive	Autosomal dominant	[5]
TUBB1	TT63KYR	Supportive	Autosomal dominant	[2]
ITGB3	TTJA1ZO	Strong	Genetic Variation	[6]
TUBB1	TT63KYR	Definitive	GermlineCausalMutation	[2]
------------------------------------------------------------------------------------


⏷ Show the Full List of 6 DTT(s)

References

1	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.
2	Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly. Blood. 2009 Jan 8;113(2):458-61. doi: 10.1182/blood-2008-06-162610. Epub 2008 Oct 10.
3	Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIb (Bolzano mutation). Haematologica. 2012 Jan;97(1):82-8. doi: 10.3324/haematol.2011.050682. Epub 2011 Sep 20.
4	A nonsynonymous SNP in the ITGB3 gene disrupts the conserved membrane-proximal cytoplasmic salt bridge in the alphaIIbbeta3 integrin and cosegregates dominantly with abnormal proplatelet formation and macrothrombocytopenia. Blood. 2008 Apr 1;111(7):3407-14. doi: 10.1182/blood-2007-09-112615. Epub 2007 Dec 7.
5	Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg(2+) homeostasis and cytoskeletal architecture. Nat Commun. 2016 Mar 29;7:11097. doi: 10.1038/ncomms11097.
6	A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin IIb3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction.Ann Hematol. 2018 Apr;97(4):629-640. doi: 10.1007/s00277-017-3214-4. Epub 2018 Jan 29.
7	ACTN1 mutations cause congenital macrothrombocytopenia. Am J Hum Genet. 2013 Mar 7;92(3):431-8. doi: 10.1016/j.ajhg.2013.01.015. Epub 2013 Feb 21.
8	GFI1B mutation causes a bleeding disorder with abnormal platelet function. J Thromb Haemost. 2013 Nov;11(11):2039-47. doi: 10.1111/jth.12368.
9	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.
10	Heterozygous ITGA2B R995W mutation inducing constitutive activation of the IIb3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia. Blood. 2011 May 19;117(20):5479-84. doi: 10.1182/blood-2010-12-323691. Epub 2011 Mar 31.
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	Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome).Blood. 2001 Feb 15;97(4):1147-9. doi: 10.1182/blood.v97.4.1147.