Increased incidence of germline PIEZO1 mutations in individuals with idiopathic erythrocytosis

TO THE EDITOR:

Erythrocytosis and polycythemia are generic terms for red cell diseases characterized by an increase in hematocrit (Ht) and/or hemoglobin (Hb) concentrations. They can be acquired as primary polycythemia vera, as a secondary disease resulting from an adaptive response to hypoxia, or as certain erythropoietin (EPO)-secreting tumors. On the other hand, congenital secondary erythrocytosis can result from mutations in the genes encoding (1) high-oxygen-affinity Hb; (2) proteins involved in the oxygen-sensing pathway, or, rarely; (3) bisphosphoglycerate mutase leading to decreased 2,3-DPG levels.¹  However, despite the recent use of next-generation sequencing (NGS), the underlying cause is found in only ∼25% of cases of congenital erythrocytosis.^2-4 

Recently, patients with elevated Ht and Hb concentrations have been reported in hereditary xerocytosis (HX) associated with a PIEZO1/FAM38A mutation.^5-9 PIEZO1 is the gene encoding the transmembrane nonselective cationic PIEZO1 channel, which...