title: Investigation of genetic disturbances in oxygen sensing and erythropoietin signaling pathways in cases of idiopathic erythrocytosis.
abstract: 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.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, 05403-000 São Paulo, SP, Brazil.
authors.forename: Carla Luana
authors.initials: CL
authors.lastname: Dinardo
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, 05403-000 São Paulo, SP, Brazil.
authors.forename: Paulo Caleb Junior Lima
authors.initials: PC
authors.lastname: Santos
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, 05403-000 São Paulo, SP, Brazil ; Novo Atibaia Hospital, 05403-000 São Paulo, SP, Brazil.
authors.forename: Isolmar Tadeu
authors.initials: IT
authors.lastname: Schettert
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, 05403-000 São Paulo, SP, Brazil.
authors.forename: Renata Alonso Gadi
authors.initials: RA
authors.lastname: Soares
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, 05403-000 São Paulo, SP, Brazil.
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, 05403-000 São Paulo, SP, Brazil.
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira