To test the spacer-nick system on clinically relevant loci in primary immune cells, we focused on a set of known mutations in the HBB, ELANE, IL7R, and PRF1 genes that are known to cause beta thalassemia, severe congenital neutropenia, severe combined immune deficiency, and familial hemophagocytic lymphohistiocytosis, respectively. Here, HBB is linked to hereditary hemophagocytic lymphohistiocytosis.