| H01740 | |
| H number | H01740 |
| Name | Macrothrombocytopenia |
| Description | Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. The clinical presentations of MTP-affected individuals vary considerably and range from no symptoms to a severe bleeding tendency. MTP-causing mutations have been reported in several genes, involved in various functions such as cell signaling, cytoskeleton organization, and gene expression. Among these, the most common is MYH9, which is responsible for MYH9-related disease. The second most common are GP1BA, GP1BB, and GP, which are responsible for Bernard-Soulier syndrome. |
| Category | Hematologic disease |
| Network | nt06515(H01740) Regulation of kinetochore-microtubule interactions |
| Gene | (MATINS) MYH9 [HSA:4627] [KO:K10352] (BSS) GP1BA [HSA:2811] [KO:K06261] (BSS) GP1BB [HSA:2812] [KO:K06262] (BSS) GP9 [HSA:2815] [KO:K06263] (BDPLT15) ACTN1 [HSA:87] [KO:K05699] (BDPLT16) ITGA2B [HSA:3674] [KO:K06476] (BDPLT19) PRKACG [HSA:5568] [KO:K04345] (BDPLT24) ITGB3 [HSA:3690] [KO:K06493] (STSL1) ABCG8 [HSA:64241] [KO:K05684] (STSL2) ABCG5 [HSA:64240] [KO:K05683] (MACTHC1) TUBB1 [HSA:81027] [KO:K07375] (MACTHC2) TUBA8 [HSA:51807] [KO:K07374] GATA1 [HSA:2623] [KO:K09182] VWF [HSA:7450] [KO:K03900] DIAPH1 [HSA:1729] [KO:K05740] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 3B64.01 ICD-10: D69.6 MeSH: D013921 OMIM: 155100 231200 615193 187800 616176 619271 210250 618666 613112 619840 300367 613554 124900 |
| Reference | PMID:25944497 (MYH9, BSS) AUTHORS Favier R, Raslova H TITLE Progress in understanding the diagnosis and molecular genetics of macrothrombocytopenias. JOURNAL Br J Haematol 170:626-39 (2015) DOI:10.1111/bjh.13478 PMID:23434115 (BDPLT15) AUTHORS Kunishima S, Okuno Y, Yoshida K, Shiraishi Y, Sanada M, Muramatsu H, Chiba K, Tanaka H, Miyazaki K, Sakai M, Ohtake M, Kobayashi R, Iguchi A, Niimi G, Otsu M, Takahashi Y, Miyano S, Saito H, Kojima S, Ogawa S TITLE ACTN1 mutations cause congenital macrothrombocytopenia. JOURNAL Am J Hum Genet 92:431-8 (2013) DOI:10.1016/j.ajhg.2013.01.015 PMID:22102273 (BDPLT16_24) AUTHORS Nurden AT, Pillois X, Fiore M, Heilig R, Nurden P TITLE Glanzmann thrombasthenia-like syndromes associated with Macrothrombocytopenias and mutations in the genes encoding the alphaIIbbeta3 integrin. JOURNAL Semin Thromb Hemost 37:698-706 (2011) DOI:10.1055/s-0031-1291380 PMID:25323684 (BDPLT19) AUTHORS Landolt-Marticorena C, Kahr WH TITLE Inherited macrothrombocytopenias on the rise. JOURNAL Blood 124:2473-5 (2014) DOI:10.1182/blood-2014-08-592329 PMID:24166850 (STSL1_2) AUTHORS Wang Z, Cao L, Su Y, Wang G, Wang R, Yu Z, Bai X, Ruan C TITLE Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia. JOURNAL Am J Hematol 89:320-4 (2014) DOI:10.1002/ajh.23619 PMID:18849486 (TUBB1) AUTHORS Kunishima S, Kobayashi R, Itoh TJ, Hamaguchi M, Saito H TITLE Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly. JOURNAL Blood 113:458-61 (2009) DOI:10.1182/blood-2008-06-162610 PMID:34704371 (TUBA8) AUTHORS Kimmerlin Q, Dupuis A, Bodakuntla S, Weber C, Heim V, Henriot V, Moog S, Eckly A, Gueguen P, Ferec C, Gachet C, Janke C, Lanza F TITLE Mutations in the most divergent alpha-tubulin isotype, alpha8-tubulin, cause defective platelet biogenesis. JOURNAL J Thromb Haemost 20:461-469 (2022) DOI:10.1111/jth.15573 PMID:11809723 (GATA1) AUTHORS Freson K, Matthijs G, Thys C, Marien P, Hoylaerts MF, Vermylen J, Van Geet C TITLE Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation. JOURNAL Hum Mol Genet 11:147-52 (2002) DOI:10.1093/hmg/11.2.147 PMID:19060241 (VWF) AUTHORS Jackson SC, Sinclair GD, Cloutier S, Duan Z, Rand ML, Poon MC TITLE The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation. JOURNAL Blood 113:3348-51 (2009) DOI:10.1182/blood-2008-06-165233 PMID:26912466 (DIAPH1) AUTHORS Stritt S, Nurden P, Turro E, Greene D, Jansen SB, Westbury SK, Petersen R, Astle WJ, Marlin S, Bariana TK, Kostadima M, Lentaigne C, Maiwald S, Papadia S, Kelly AM, Stephens JC, Penkett CJ, Ashford S, Tuna S, Austin S, Bakchoul T, Collins P, Favier R, Lambert MP, Mathias M, Millar CM, Mapeta R, Perry DJ, Schulman S, Simeoni I, Thys C, Gomez K, Erber WN, Stirrups K, Rendon A, Bradley JR, van Geet C, Raymond FL, Laffan MA, Nurden AT, Nieswandt B, Richardson S, Freson K, Ouwehand WH, Mumford AD TITLE A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss. JOURNAL Blood 127:2903-14 (2016) DOI:10.1182/blood-2015-10-675629 |