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Abstract
Pathogenic/likely pathogenic (P/LP) germline variants in RUNX1 cause familial platelet disorder with associated myeloid malignancies (FPDMM), also known as RUNX1-Familial Platelet Disorder (RUNX1-FPD, or FPD), a condition characterized by qualitative and quantitative platelet defects and predisposition to hematopoietic malignancies. Here, we present follow up to a case of a woman with acute myeloid leukemia and lifelong thrombocytopenia which had previously been attributed to presumptive pathogenic (P) GATA2 missense variants. However, re-evaluation with updated molecular technology sensitive for detection of copy number variants (CNVs) led to the identification of a P deletion of exons 5-6 in RUNX1, which had been undetected when examined at first presentation. This case highlights the importance of comprehensive molecular evaluation and careful variant interpretation, especially regarding CNVs.
Details
1 NIH, Oncogenesis and Development Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, USA (GRID:grid.280128.1) (ISNI:0000 0001 2233 9230)
2 University of Washington School of Medicine, Laboratory Medicine & Pathology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657)
3 SA Pathology and University of South Australia, Centre for Cancer Biology, Adelaide, Australia (GRID:grid.470344.0) (ISNI:0000 0004 0450 082X)
4 NIH, Translational Stem Cell Biology Branch, National Heart Lung and Blood Institute, Bethesda, USA (GRID:grid.279885.9) (ISNI:0000 0001 2293 4638)
5 Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Division of Hematology/Oncology, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)