Genetic Classification and Confirmation of Inherited Platelet Disorders and Current Status in Korea

Abstract

Inherited platelet disorders (IPDs), which manifest as primary hemostasis defects, often underlie abnormal bleeding and a family history of thrombocytopenia, bone marrow failure, hematologic malignancies, undefined mucocutaneous bleeding disorder, or congenital bony defects. A wide heterogeneity in IPD types, in regard to the presence or absence of thrombocytopenia, platelet dysfunction, bone marrow failure, and dysmegakaryopoiesis, is observed in patients. The individual processes involved in platelet production and hemostasis are genetically controlled: to date, mutations more than 50 genes involved in various steps of platelet biogenesis have been implicated in IPDs. Representative IPDs resulting from defects in specific pathways, such as THPO/MPL signaling; transcriptional regulation; granule formation, trafficking, and secretion; proplatelet formation; cytoskeleton regulation; and transmembrane GP signaling, are reviewed, and the underlying gene mutations discussed based on the NCBI database and Online Mendelian Inheritance in Man accession number (OMIM). Further, the status and prevalence of genetically confirmed IPDs in Korea are explored based on the literature searches of PubMed and KoreaMed database. IPDs are congenital bleeding disorders that can be dangerous due to unexpected bleeding and also requires genetic counseling for family members and descendants. Therefore, the pediatrician should be suspicious and aware of IPDs and able to carry out appropriate tests if the patient has an unexpected bleeding. However, each disease of IPDs are extremely rare, thus the domestic incidence of IPDs are unclear and it is difficult to diagnose IPDs. Diagnostic confirmation or differential diagnoses of IPDs are challenging, time-consuming, and expensive, and patients are frequently misdiagnosed. Comprehensive molecular characterization and classification for these disorders should enable accurate and precise diagnosis and facilitate improved patient management.