%0 Journal Article
%T Investigation of Genetic Disturbances in Oxygen Sensing and Erythropoietin Signaling Pathways in Cases of Idiopathic Erythrocytosis
%A Carla Luana Dinardo
%A Paulo Caleb Junior Lima Santos
%A Isolmar Tadeu Schettert
%A Renata Alonso Gadi Soares
%A Jose Eduardo Krieger
%A Alexandre Costa Pereira
%J Genetics Research International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/495724
%X 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¦Á genes using bidirectional sequencing of their hotspots. Results. One case was associated with HIF-2¦Á 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¦Á p.N636N, rs35606117; HIF-2¦Á 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. 1. Introduction Absolute erythrocytosis should be suspected when hemoglobin (Hb) is greater than 16.5£¿g/dL in females or 18.0£¿g/dL in males [1] and defines a status of elevated hemoglobin. Causes of erythrocytosis can be divided into two groups: primary, in which there is an intrinsic problem in bone marrow driving abnormal erythropoiesis, or secondary, in which there is an event outside bone marrow leading to an abnormal production of erythrocytes [1]. Both groups can be further classified into acquired or congenital. Within the group of primary erythrocytosis, erythropoietin receptor (EPOR) mutation (congenital) and polycythemia vera (PV, acquired) stand out. Within the group of secondary erythrocytosis, there are multiple acquired causes (hypoxia, EPO pathologic production, and drugs) and a restricted subgroup of congenital causes (VHL, PHD2, and HIF-2¦Á mutations; high oxygen-affinity hemoglobin; and bisphosphoglycerate mutase deficiency) (Figure 1) [1¨C3]. Figure 1: Representation of diagnostic strategy for patients with erythrocytosis without acquired secondary causes. The most common example of primary erythrocytosis is polycythemia vera (PV). Notably, the majority of idiopathic erythrocytosis patients cannot be classified into the OMIM
%U http://www.hindawi.com/journals/gri/2013/495724/