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.
Thieme Medical Publishers.