Sarah A Cook, William A Comrie, M Cecilia Poli, Morgan Similuk, Andrew J Oler, Aiman J Faruqi, Douglas B Kuhns, Sheng Yang, Alexander Vargas-Hernández, Alexandre F Carisey, Benjamin Fournier, D Eric Anderson, Susan Price, Margery Smelkinson, Wadih Abou Chahla, Lisa R Forbes, Emily M Mace, Tram N Cao, Zeynep H Coban-Akdemir, Shalini N Jhangiani, Donna M Muzny, Richard A Gibbs, James R Lupski, Jordan S Orange, Geoffrey D E Cuvelier, Moza Al Hassani, Nawal Al Kaabi, Zain Al Yafei, Soma Jyonouchi, Nikita Raje, Jason W Caldwell, Yanping Huang, Janis K Burkhardt, Sylvain Latour, Baoyu Chen, Gehad ElGhazali, V Koneti Rao, Ivan K Chinn, Michael J Lenardo
Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in NCKAP1L , which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration...
July 10, 2020: Science