Macrothrombocytopenia

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

MYH9 [HSA:4627] [KO:K10352]
GP1BA [HSA:2811] [KO:K06261]
GP1BB [HSA:2812] [KO:K06262]
GP9 [HSA:2815] [KO:K06263]
ITGA2B [HSA:3674] [KO:K06476]
ITGB3 [HSA:3690] [KO:K06493]
FLNA [HSA:2316] [KO:K04437]
GATA1 [HSA:2623] [KO:K09182]
TUBB1 [HSA:81027] [KO:K07375]
NBEAL2 [HSA:23218] [KO:K23286]
VWF [HSA:7450] [KO:K03900]
GFI1B [HSA:8328] [KO:K09223]
ACTN1 [HSA:87] [KO:K05699]
ABCG5 [HSA:64240] [KO:K05683]
ABCG8 [HSA:64241] [KO:K05684]
PRKACG [HSA:5568] [KO:K04345]
DIAPH1 [HSA:1729] [KO:K05740]

See also H00233 MYH9-related disease, H00224 Bernard-Soulier syndrome, and H01235 Bleeding disorder platelet-type.

PMID:25944497

Favier R, Raslova H

Progress in understanding the diagnosis and molecular genetics of macrothrombocytopenias.

Br J Haematol 170:626-39 (2015)
DOI:10.1111/bjh.13478

PMID:23434115

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)
DOI:10.1016/j.ajhg.2013.01.015

PMID:26912466

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)
DOI:10.1182/blood-2015-10-675629