Familial erythrocytosis (FE) is a congenital disorder, defined by elevated red blood cell number, hemoglobin and hematocrit. Among eight types of FE, type 4 is caused by variants in the EPAS1 gene. Two other hypoxia-inducible factor alpha (HIFA) subunits, HIF1A and HIF3A have not yet been associated with medical history of FE, but have potential role in development of erythrocytosis. To improve diagnosis it is crucial to identify new variants in genes involved in erythrocyte production. Published literature and data from genome browsers were used to obtain HIFA sequence variants associated with erythrocytosis and to locate them on protein sequence and regulatory sites. We retrieved 24 variants from the literature: 2 in HIF1A, 20 in EPAS1 and 2 variants in HIF3A gene. Sixteen out of 20 variants in the EPAS1 gene are positioned in a conserved region of 13 amino acids within exon 12, next to regulatory post-translational modification and binding sites. The most important variants for development of erythrocytosis are present in a region of 13 amino acids in exon 12 of the EPAS1 gene, suggesting that EPAS1 has an important role in erythropoiesis. The role of HIF1A and HIF3A in the development of erythrocytosis should be further investigated.
COBISS.SI-ID: 34438105
Objectives: Erythrocytosis is characterized by the expansion of erythrocyte compartment including elevated red blood cell number, hematocrit, and hemoglobin content. Familial erythrocytosis (FE) is a congenital disorder with different genetic background. Type 1 FE is primary FE caused by mutation in erythropoietin receptor gene (EPOR). Type 2-5 FE are secondary FEs caused by mutations of genes involved in oxygen sensing pathway important for erythropoietin (EPO) regulation. In the present study we summarized associations between EPOR and EPO gene variations with development of FE and searched for genetic variants located within regulatory regions. Methods: Publications reporting EPOR and EPO sequence variants associated with FE or clinical features of erythrocytosis were retrieved from PubMed and WoS. In silico sequence reanalysis was performed using Ensembl genomic browser, release 89 to screen for variants located within regulatory regions. Results: To date 28 variants of the EPOR and seven variants of the EPO gene have been associated with erythrocytosis or upper hematocrit. Sequence variants were also found to be present within regulatory regions. Conclusions: Role of variants in regulatory regions of the EPO gene should be further investigated.
COBISS.SI-ID: 4158600
Erythrocytosis is a condition characterized by increased red blood cell mass in the body. Patients usually present with increased hematocrit, increased hemoglobin concentration and an increased number of red blood cells. Erythrocytosis can be absolute or relative. Absolute erythrocytosis is either primary or secondary, both groups are further divided into congenital and acquired. The characterization is often problematic and etiology remains unknown in many patients; resulting in an entity “idiopathic erythrocytosis”. The aim of this article is to improve the diagnostic methods for erythrocytosis including further genetic testing into routine clinical practice. We propose an extended and detailed algorithm for diagnosis of erythrocytosis. We describe the classification of various forms of erythrocytoses, clinical presentation, genetic background, diagnostic methods and treatment options. By reviewing the 5-year period of JAK2 mutation testing (the first laboratory test performed in a patient with erythrocytosis) we obtained better insight into prevalence of the disease in Slovenia.
COBISS.SI-ID: 34416601