Background. Idiopathic
erythrocytosis is the term reserved for cases with unexplained origins of abnormally increased
hemoglobin after initial investigation. Extensive molecular investigation of genes associated with
oxygen sensing and
erythropoietin signaling pathways, in those cases, usually involves sequencing all of their exons and it may be time consuming. Aim. To perform a strategy for molecular investigation of patients with idiopathic
erythrocytosis regarding
oxygen sensing and
erythropoietin signaling pathways. Methods. Samples of patients with idiopathic
erythrocytosis were evaluated for the EPOR, VHL, PHD2, and HIF-2 α genes using bidirectional sequencing of their hotspots. Results. One case was associated with HIF-2 α mutation. Sequencing did not identify any pathogenic mutation in 4 of 5 cases studied in any of the studied genes. Three known nonpathogenic polymorphisms were found (VHL p.P25L, rs35460768; HIF-2 α p.N636N, rs35606117; HIF-2 α p.P579P, rs184760160). Conclusion. Extensive molecular investigation of cases considered as idiopathic
erythrocytosis does not frequently change the treatment of the patient. However, we propose a complementary molecular investigation of those cases comprising genes associated with
erythrocytosis phenotype to meet both academic and genetic counseling purposes.