Abstract Number: PB0869
Meeting: ISTH 2021 Congress
Background: Recent identification of the molecular basis of many forms of inherited thrombocytopenia (IT) suggests that this is a heterogeneous group of disorders affecting megakaryocytic differentiation and/or platelets production. Various forms of the disorder differ in bleeding tendency, non-hematological manifestations and the risk of malignant transformation. Next generation sequencing (NGS) techniques are offering accurate cost-effective molecular diagnosis of those disorders, which is essential for appropriate therapy and follow-up.
Aims: We used targeted NGS to diagnose IT in patients referred to us because of persistent or congenital thrombocytopenia with or without family history of thrombocytopenia and with no features of myelodysplastic syndrome.
Methods: Genetic diagnosis was performed by using a customized targeted NGS panel including of 45 genes known when mutated to cause IT.
Results: Genetic diagnosis was achieved in 18 out of 31 patients (58.1%). Of those, six (33.3%) patients were diagnosed with MYH9-related disorder, two had mutations in ACTN1, one in NBEAL2, one in ITG3B, one in GALE and one in CYCS gene. Six patients were diagnosed as having inherited predisposition to MDS/AML (4 with ANKD26 mutations, one with ETV6 and one with RUNX1 mutation). Molecular diagnosis of the propositus led to a genetic diagnosis of IT in other family members. Interestingly, four patients out of 8 originally diagnosed as having chronic ITP, were found to have IT.
Conclusions: In our cohort, MYH9-related disorders were found in a third of the patients who were molecularly diagnosis as having IT. Those patients should be carefully monitored, as they are prone to develop kidney failure later in life. A third of the patients were found to have predisposition to MDS/AML. They should be followed carefully for signs of MDS and stem cell transplantation should be considered prior to development of AML. Further molecular analysis of patients with IT is indicated to optimize treatment and follow up.
To cite this abstract in AMA style:Gilad O, Steinberg - Shemer O, Dgany O, Krasnov T, Noy - Lotan S, Yacobovich J, Tamary H. Targeted Next Generation Sequencing for the Diagnosis of Patients with Inherited Thrombocytopenias [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/targeted-next-generation-sequencing-for-the-diagnosis-of-patients-with-inherited-thrombocytopenias/. Accessed February 27, 2024.
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