The Novel Piezo1 Mutation P.L2023v Is Causal For Hereditary Xerocytosis Resulting In Delayed Channel Inactivation And A Dehydrated Red Blood Cell Phenotype

The regulation of cell volume is important for the maintenance of integrity in all cells and is especially critical for the highly specialized red blood cell (RBC) which must withstand pressure changes within the vasculature and remain deformable to traverse small vessels. Disorders that interfere with volume homeostasis result in the premature destruction of RBCs. One protein that appears to play a prominent role in RBC hydration is the recently described nonselective cation channel PIEZO1 which is involved in mechanotransduction. Mutations of PIEZO1 have been associated with an autosomal dominant form of hereditary hemolytic anemia (HHA) characterized by RBC dehydration known as hereditary xerocytosis (HX) (Zarychanski et al., Blood 2012;120:1908). There is evidence that PIEZO1 may also be responsible for a channel activity that participates in the dehydration of sickle cells which exacerbates sickling and vaso-occlusive events in patients with Sickle Cell Disease (reviewed in Gallagher, Curr Opin Hematol 2013, 20:201).