Identification of Two Novel EPOR Gene Variants in Primary Familial Polycythemia: Case Report and Literature Review

SIMPLE SUMMARY: Erythrocytosis can be caused by a wide variety of diseases. Some forms of erythrocytosis have an obvious cause, such as a kidney injury, or it may have an oncological cause, but in some patients, the origin of the disease is not entirely clear, and since the symptoms of an isolated erythrocytosis are not usually cumbersome, sometimes the diagnosis takes several months or years. In the present work, we report a couple of cases of familial erythrocytosis associated with novel variants in the erythropoietin receptor gene. This study serves as a reminder of the clinical and molecular study of this rare disease and expands the list of mutations associated with primary familial polycythemia. ABSTRACT: Primary familial and congenital polycythemia is a rare disease characterized by an increase in red cell mass that may be due to pathogenic variants in the EPO receptor (EPOR) gene. To date, 33 genetic variants have been reported to be associated. We analyzed the presence of EPOR variants in two patients with polycythemia in whom JAK2 pathogenic variants had been previously discarded. Molecular analysis of the EPOR gene was performed by Sanger sequencing of the coding regions and exon/intron boundaries of exon 8. We performed in vitro culture of erythroid progenitor cells. Segregation studies were done whenever possible. The two patients studied showed hypersensitivity to EPO in in vitro cultures. Analysis of the EPOR gene unveiled two novel pathogenic variants. Genetic testing of asymptomatic relatives could guarantee surveillance and proper management.