Department of Pediatrics, Human Medical Genetics Program, University of Colorado, Denver, Colorado, USA.
Semin Thromb Hemost. 2011 Sep;37(6):690-7. doi: 10.1055/s-0031-1291379. Epub 2011 Nov 18.
Over the last two decades the genetic causes of several Mendelian platelet disorders have been elucidated, while the genetics of many other thrombocytopenic conditions are still unresolved. Among those are the gray platelet syndrome (GPS) and the thrombocytopenia linked to the THC2 locus on human chromosome 10p11-12. GPS is an α-granule defect associated with the development of myelofibrosis and mild to moderate thrombocytopenia. Most forms of GPS are autosomal recessive, and recently, the recessive form of the disease was mapped to chromosome 3p21. THC2-linked thrombocytopenia is an autosomal dominant disorder in which affected family members have a mild reduction in platelet counts and occasional bleeding. Platelets in THC2-linked thrombocytopenia appear to be normal in size and function although bone marrow morphology reveals a lack of mature, polyploid megakaryocytes. To date, mutations in three different genes within the THC2 locus have been associated with congenital thrombocytopenia, including a mutation in MASTL. In this article, we summarize the recent discoveries in these two forms of thrombocytopenia, including the functional data that support a role for MASTL kinase in thrombopoiesis.
在过去的二十年中，已经阐明了几种孟德尔血小板疾病的遗传原因，而许多其他血小板减少症的遗传原因仍未解决。其中包括灰色血小板综合征 (GPS) 和与人类染色体 10p11-12 上的 THC2 基因座相关的血小板减少症。GPS 是一种与骨髓纤维化和轻至中度血小板减少症发展相关的α-颗粒缺陷。大多数形式的 GPS 是常染色体隐性遗传的，最近，该疾病的隐性形式被定位到 3p21 染色体上。THC2 相关的血小板减少症是一种常染色体显性疾病，受影响的家族成员血小板计数轻度减少，偶尔会出现出血。THC2 相关血小板减少症的血小板在大小和功能上似乎正常，尽管骨髓形态学显示缺乏成熟的多倍体巨核细胞。迄今为止，已经在 THC2 基因座内的三个不同基因中发现了与先天性血小板减少症相关的突变，包括 MASTL 突变。本文总结了这两种形式血小板减少症的最新发现，包括支持 MASTL 激酶在造血中的作用的功能数据。
