Molecular basis of inherited thrombocytopenias: an update

Abstract

Purpose of review: Inherited thrombocytopenias are a heterogeneous group of diseases caused by mutations in many genes. They account for approximately only 50% of cases, suggesting that novel genes have yet to be identified for a comprehensive understanding of platelet biogenesis defects. This review provides an update of the last year of discoveries on inherited thrombocytopenias focusing on the molecular basis and potential pathogenic mechanisms affecting megakaryopoiesis and platelet production.

Recent findings: Most of the novel discoveries are related to identification of mutations in novel inherited thrombocytopenia genes using a next-generation sequencing approach. They include MECOM, DIAPH1, TRPM7, SRC, FYB, and SLFN14, playing different roles in megakaryopoiesis and platelet production. Moreover, it is worth mentioning data on hypomorphic mutations of FLI1 and the association of single nucleotide polymorphisms, such as that identified in ACTN1, with thrombocytopenia.

Summary: Thanks to the application of next-generation sequencing, the number of inherited thrombocytopenia genes is going to increase rapidly. Considering the wide genetic heterogeneity (more than 30 genes), these technologies can also be used for diagnostic purpose. Whatever is the aim, extreme caution should be taken in interpreting data, as inherited thrombocytopenias are mainly autosomal dominant diseases caused by variants of apparent unknown significance.