In eLife, a team at Radboud University Medical Center, the University Medical Center Groningen, and other centers present findings from a retrospective exome sequencing-based analysis of sporadic inborn errors of immunity cases. Based on protein-coding sequences for 123 suspect inborn errors of immunity patients along with corresponding exome sequences from proband parents, the researchers found apparent genetic culprits in a dozen of the inborn errors of immunity cases, focusing in on 14 de novo variant candidates falling in inborn errors of immunity genes such as NLRP3 or RELA as well as other candidate genes with ties to the immune system. When they assessed a splice site change in FBXW11 in immune cells from an autoinflammatory disease patient, for example, the authors detected downstream signaling shifts and enhanced production of the pro-inflammatory cytokine interleukin IL-1-beta. Based on these and other findings, they say, "[w]e advocate the structural implementation of trio-based sequencing in the diagnostic evaluation of patients with sporadic [inborn errors of immunity]."
Trio Exomes Used to Detect De Novo Variants in Inborn Errors of Immunity
Oct 18, 2022