Macrothrombocytopenia associated with a rare GFI1B missense variant confounding the presentation of immune thrombocytopenia

Abstract

Growth factor‐independent 1B (GFI1B) variants are a rare cause of thrombocytopenia. We report on a male child who was initially diagnosed with immune thrombocytopenia. However, subtle clinical signs led to suspicion of a genetic cause of thrombocytopenia. Gene panel sequencing revealed a rare variant in GFI1B (C168F), which has recently been reported in several families with thrombocytopenia. We demonstrate that this variant significantly alters platelet parameters in population studies. This case highlights how diagnoses of exclusion, such as immune thrombocytopenia, can be confounded by genetic variation. Our understanding of blood disorders will undoubtedly evolve from an increased knowledge of human genetic variation.

Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling

“…Definitive megakaryocytes emerge from HSC-derived common myeloid progenitors that also form erythrocytes plus mast cells and myeloblasts 25,[34][35][36] . The Gfi1 transcription factors have been implicated in controlling hematopoietic lineage progression in human and mouse: Gfi1b predominantly drives megakaryocyte differentiation by suppressing erythroid fate, with missense mutations in human GFI1B causing thrombocytopenia [37][38][39] . In zebrafish, the orthologs gfi1aa and gfi1b contribute to primitive erythropoiesis and are expressed in erythroid, intermediate erythroid-myeloid progenitors (EMPs), and emerging hematopoietic stem cells [40][41][42] .…”