Gain-of-function IKBKB mutation causes human combined immune deficiency.

ABSTRACT: Genetic mutations account for many devastating early onset immune deficiencies. In contrast, less severe and later onset immune diseases, including in patients with no prior family history, remain poorly understood. Whole exome sequencing in two cohorts of such patients identified a novel heterozygous de novo IKBKB missense mutation (c.607G>A) in two separate kindreds in whom probands presented with immune dysregulation, combined T and B cell deficiency, inflammation, and epithelial defects. IKBKB encodes IKK2, which activates NF-κB signaling. IKK2^V203I results in enhanced NF-κB signaling, as well as T and B cell functional defects. IKK2^V203 is a highly conserved residue, and to prove causation, we generated an accurate mouse model by introducing the pre

SUBMITTER: Cardinez C 

PROVIDER: S-EPMC6219745 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature