biostudies-literatureKlemann CBundesministerium für Bildung und ForschungEuropean Research Council52-6https://www.ebi.ac.uk/biostudies/studies/S-EPMC6101191biostudies-literatureUnknown164NF-κB essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant NEMO allele associated with symptoms of Behçet's disease. Hematopoietic stem cell transplantation of an affected boy from this donor reconstituted an immune system with retained skewed X-inactivation. After transplantation no more severe infections occurred, indicating that an active wild-type NEMO allele in only 10% of immune cells restores host defense. Yet he developed inflammatory bowel disease (IBD). While gut infiltrating immune cells stained strongly for nuclear p65 indicating restored NEMO functClinical immunology (Orlando, Fla.)Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency.PMC6101191BMBF 01 EO 0803323040Ehl SRizzi MRohr JCSpeckmann CVlantis KVraetz TPasparakis MKlemann CUhlig HStrahm BMorris-Rosendahl DJPannicke USchwarz KfalseTransplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency.NF-κB essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant NEMO allele associated with symptoms of Behçet's disease. Hematopoietic stem cell transplantation of an affected boy from this donor reconstituted an immune system with retained skewed X-inactivation. After transplantation no more severe infections occurred, indicating that an active wild-type NEMO allele in only 10% of immune cells restores host defense. Yet he developed inflammatory bowel disease (IBD). While gut infiltrating immune cells stained strongly for nuclear p65 indicating restored NEMO funct2016-01-01T00:00:00Z2016 Mar2025-04-04T03:26:08.24Z2019-03-26T23:51:57ZS-EPMC61011912681262410.1016/j.clim.2016.01.010