Cynthia Turnbull, Josiah Bones, Maurice Stanley, Arti Medhavy, Hao Wang, Ayla May D Lorenzo, Jean Cappello, Somasundhari Shanmuganandam, Abhimanu Pandey, Sandali Seneviratne, Grant J Brown, Xiangpeng Meng, David Fulcher, Gaetan Burgio, Si Ming Man, Carmen de Lucas Collantes, Mercedes Gasior, Eduardo López Granados, Pilar Martin, Simon H Jiang, Matthew C Cook, Julia I Ellyard, Vicki Athanasopoulos, Ben Corry, Pablo F Canete, Carola G Vinuesa
Autosomal dominant loss-of-function (LoF) variants in cytotoxic T-lymphocyte associated protein 4 ( CTLA4 ) cause immune dysregulation with autoimmunity, immunodeficiency and lymphoproliferation (IDAIL). Incomplete penetrance and variable expressivity are characteristic of IDAIL caused by CTLA-4 haploinsufficiency (CTLA-4h), pointing to a role for genetic modifiers. Here, we describe an IDAIL proband carrying a maternally inherited pathogenic CTLA4 variant and a paternally inherited rare LoF missense variant in CLEC7A, which encodes for the β-glucan pattern recognition receptor DECTIN-1...
December 8, 2023: Science Advances