KEGG   DISEASE: Macrothrombocytopenia
Entry
H01740                      Disease                                
Name
Macrothrombocytopenia
  Subgroup
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)
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
Brite
Human diseases [BR:br08402]
 Cardiovascular diseases
  Hematologic diseases
   H01740  Macrothrombocytopenia
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
Related
pathway
hsa04611  Platelet activation
hsa04640  Hematopoietic cell lineage
hsa04510  Focal adhesion
hsa04512  ECM-receptor interaction
hsa04810  Regulation of actin cytoskeleton
hsa04151  PI3K-Akt signaling pathway
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]
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
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