Hyper-IgE syndromes What every physician needs to know: There are two major diseases included under the heading of hyper-IgE syndromes (HIES): STAT3 deficiency (autosomal dominant HIES or Job’s syndrome) and DOCK8 deficiency (autosomal recessive HIES). Job’s syndrome is due to heterozygous dominant-negative mutations in STAT3, a major transcription factor, that lead to impaired inflammation with…
Toll-like receptor signaling defects What every physician needs to know: This chapter discusses Toll-like receptor signaling defects (interleukin-1 receptor-associated kinase 4 [IRAK-4], myeloid differentiation primary response gene [88] [MYD88], NF-kappa-B essential modulator [NEMO]). Signal transduction both to generate and to perpetuate inflammation requires the activation of nuclear factor kappa B (NFkB). Therefore, defects along this…
Disorders of neutrophils: GATA2 Deficiency (also known as MonoMAC, DCML, Emberger, familial AML/MDS, classical NK cell deficiency) What every physician needs to know: GATA2 is a critical transcription factor in early hematopoietic ontogeny. Haploinsufficiency for GATA2 causes conditions ranging from deafness to lymphedema to acute myelogenous leukemia to disseminated mycobacterial infection, with ages of onset…
