Identifying hematologic diseases using WES. (A) Blood smear from a patient with HX demonstrates rare stomatocytes, target cells, and dessicytes (dense, erythrocytes with hemoglobin appearing to be puddled at the periphery). (B) WES identified mutations in PIEZO1, encoded by the FAM38A gene, as the HX disease locus. The location of this patient’s mutation is denoted by the arrow on a model of PIEZO1 created using hmmtop2 software. Adapted from Zarychanski et al³⁵  with permission. (C) Blood marrow aspirate smear from a patient with DBA demonstrates only rare erythroblasts. (D) WES identified mutations in the GATA1 gene, leading to altered splicing and production of a short protein form of GATA1 protein (GATA1s) that lacks the NH2-terminal TD present in full-length GATA1. CF, COOH-terminal zinc finger; NF, NH2-terminal zinc finger; TD, transactivation domain. Adapted from Sankaran et al²⁸  with permission.