Characterization of a Novel Pathogenic PLCG2 Variant Leading to APLAID Syndrome Responsive to a TNF inhibitor.

Our findings demonstrated that the PLCG2 D993Y variant is a gain-of-function mutation via impairing its auto-inhibition, activating multiple inflammatory signaling pathways, thus leading to APLAID syndrome. This study further broadens the molecular underpinnings and phenotypic spectrum of PLCγ2-related disorders.