biostudies-literatureUnknown13(2)Reiff DDHemophagocytic lymphohistiocytosis (HLH) is a syndrome resulting from uncontrolled hyper-inflammation, excessive immune system activation, and elevated levels of inflammatory cytokines. HLH can be caused by the inability to downregulate activated macrophages by natural killer (NK) and CD8 cytotoxic T cells through a process reliant on perforin and granzyme B to initiate apoptosis. Homozygous genetic mutations in this process result in primary HLH (pHLH), a disorder that can lead to multi-system organ failure and death in infancy. Heterozygous, dominant-negative, or monoallelic hypomorphic mutations in these same genes can cause a similar syndrome in the presence of an immune trigger, leading to secondary HLH (sHLH). A genetic mutation in a potential novel HLH-associated gene, dedicator of Life (Basel, Switzerland)434https://www.ebi.ac.uk/biostudies/studies/S-EPMC9962445biostudies-literature<i>DOCK2</i> Mutation and Recurrent Hemophagocytic Lymphohistiocytosis.PMC9962445Reiff DDCron RQZhang Mfalse<i>DOCK2</i> Mutation and Recurrent Hemophagocytic Lymphohistiocytosis.Hemophagocytic lymphohistiocytosis (HLH) is a syndrome resulting from uncontrolled hyper-inflammation, excessive immune system activation, and elevated levels of inflammatory cytokines. HLH can be caused by the inability to downregulate activated macrophages by natural killer (NK) and CD8 cytotoxic T cells through a process reliant on perforin and granzyme B to initiate apoptosis. Homozygous genetic mutations in this process result in primary HLH (pHLH), a disorder that can lead to multi-system organ failure and death in infancy. Heterozygous, dominant-negative, or monoallelic hypomorphic mutations in these same genes can cause a similar syndrome in the presence of an immune trigger, leading to secondary HLH (sHLH). A genetic mutation in a potential novel HLH-associated gene, dedicator of 2023-01-01T00:00:00Z2023 Feb2025-04-25T23:10:20.106Z2025-04-06T09:17:53.819ZS-EPMC99624453683679110.3390/life13020434