Table 1_Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.docx

Over the past decade, advances in next-generation sequencing have markedly expanded the spectrum of disease-associated genes and revealed novel genetic mechanisms, including somatic mosaicism and non-coding variation, while also highlighting the potential contribution of multilocus rare-variant burden and modifier effects.

However, the rapid pace of gene discovery has also introduced new challenges in variant interpretation, disease classification, and clinical diagnosis. This review synthesizes findings from 100 publications published between 2014 and 2026 and summarizes recent genetic advances according to the major molecular pathways involved in autoinflammatory diseases. We review newly identified disease genes and pathogenic variants affecting ubiquitination and NF-κB regulation, inflammasome activation, type I interferon signaling, CDC42-mediated immune regulation, proteasome dysfunction, programmed cell death, cytokine signaling, and other emerging pathways.