KEGG   DISEASE: Macrothrombocytopenia
H01740                      Disease                                
MYH9-related disease (MATINS) [DS:H00233]
Bernard-Soulier syndrome (BSS) [DS:H00224]
Bleeding disorder platelet-type (BDPLT)
Sitosterolemia (STSL) [DS:H00152]
Autosomal dominant isolated macrothrombocytopenia (MACTHC)
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.
Hematologic disease
Human diseases in ICD-11 classification [BR:br08403]
 03 Diseases of the blood or blood-forming organs
  Coagulation defects, purpura or other haemorrhagic or related conditions
   3B64  Thrombocytopenia
    H01740  Macrothrombocytopenia
Pathway-based classification of diseases [BR:br08402]
 Cellular process
  nt06515  Regulation of kinetochore-microtubule interactions
   H01740  Macrothrombocytopenia
hsa04611  Platelet activation
hsa04640  Hematopoietic cell lineage
hsa04510  Focal adhesion
hsa04512  ECM-receptor interaction
hsa04810  Regulation of actin cytoskeleton
hsa04151  PI3K-Akt signaling pathway
nt06515 Regulation of kinetochore-microtubule interactions
(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]
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
PMID:25944497 (MYH9, BSS)
Favier R, Raslova H
Progress in understanding the diagnosis and molecular genetics of macrothrombocytopenias.
Br J Haematol 170:626-39 (2015)
PMID:23434115 (BDPLT15)
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
ACTN1 mutations cause congenital macrothrombocytopenia.
Am J Hum Genet 92:431-8 (2013)
PMID:22102273 (BDPLT16_24)
Nurden AT, Pillois X, Fiore M, Heilig R, Nurden P
Glanzmann thrombasthenia-like syndromes associated with Macrothrombocytopenias and mutations in the genes encoding the alphaIIbbeta3 integrin.
Semin Thromb Hemost 37:698-706 (2011)
PMID:25323684 (BDPLT19)
Landolt-Marticorena C, Kahr WH
Inherited macrothrombocytopenias on the rise.
Blood 124:2473-5 (2014)
PMID:24166850 (STSL1_2)
Wang Z, Cao L, Su Y, Wang G, Wang R, Yu Z, Bai X, Ruan C
Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia.
Am J Hematol 89:320-4 (2014)
PMID:18849486 (TUBB1)
Kunishima S, Kobayashi R, Itoh TJ, Hamaguchi M, Saito H
Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly.
Blood 113:458-61 (2009)
PMID:34704371 (TUBA8)
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
Mutations in the most divergent alpha-tubulin isotype, alpha8-tubulin, cause defective platelet biogenesis.
J Thromb Haemost 20:461-469 (2022)
PMID:11809723 (GATA1)
Freson K, Matthijs G, Thys C, Marien P, Hoylaerts MF, Vermylen J, Van Geet C
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.
Hum Mol Genet 11:147-52 (2002)
PMID:19060241 (VWF)
Jackson SC, Sinclair GD, Cloutier S, Duan Z, Rand ML, Poon MC
The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.
Blood 113:3348-51 (2009)
PMID:26912466 (DIAPH1)
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
A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss.
Blood 127:2903-14 (2016)

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