C3 and paroxysmal nocturnal hemoglobinuria: A comprehensive genetic analysis yielded three key findings: a pathogenic PIGA mutation (c.776del; p.Phe259Serfs*2), confirming the diagnosis of PNH; heterozygosity for the CR1 low-expression allele (CR1-L), a variant previously associated with increased C3 opsonization and extravascular hemolysis under C5 inhibition (8, 9); and a rare heterozygous variant in C3 (c.1514G>A; p.R505H), previously linked to aHUS (unpublished data; Table 2), which was postulated to contribute to complement dysregulation.