Brief Report RED CELLS, IRON, AND ERYTHROPOIESIS A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia that results from the expansion of hematopoietic stem cells that are deficient for glycosylphosphatidylinositol (GPI), a glycolipid moiety that anchors .100 different proteins to the cell surface. PNH patients were reported to be deficient for an initial step in the GPI anchor synthesis that is catalyzed by the GPI-GlcNAc transferase, and somatic mutations in the X-chromosomal gene PIGA that encodes a subunit of this transferase complex are regarded as the causative event in the predominant number of PNH cases. However, in a small number of PNH cases with a clear GPI anchor deficiency, no mutations in PIGA have been found. In this work, we report about 2 mutation events, a germline splice site mutation and a somatic deletion in PIGT, which is another gene of the GPI anchor synthesis pathway, that we identified performing next-generation sequencing in a PNH patient with wild-type PIGA.