Lam, Michael T.Coppola, SimonaKrumbach, Oliver H.F.Prencipe, GiusiInsalaco, AntonellaCifaldi, CristinaBrigida, ImmacolataZara, ErikaScala, SerenaDi Cesare, SilviaMartinelli, SimoneDi Rocco, MartinaPascarella, AntoniaNiceta, MarcelloPantaleoni, FrancescaCiolfi, AndreaNetter, PetraCarisey, Alexandre F.Diehl, MichaelAkbarzadeh, MohammadConti, FrancescaMerli, PietroPastore, AnnaLevi Mortera, StefanoCamerini, SerenaFarina, LuciapiaBuchholzer, MarcelPannone, LucaCao, Tram N.Coban-Akdemir, Zeynep H.Jhangiani, Shalini N.Muzny, Donna M.Gibbs, Richard A.Basso-Ricci, LucaChiriaco, MariaDvorsky, RadovanPutignani, LorenzaCarsetti, RitaJanning, PetraStray-Pedersen, AsbjorgErichsen, Hans ChristianHorne, AnnaCarinBryceson, Yenan T.Torralba-Raga, LambertoRamme, KimRosti, VittorioBracaglia, ClaudiaMessia, VirginiaPalma, PaoloFinocchi, AndreaLocatelli, FrancoChinn, Ivan K.Lupski, James R.Mace, Emily M.Cancrini, CaterinaAiuti, AlessandroAhmadian, Mohammad R.Orange, Jordan S.De Benedetti, FabrizioTartaglia, Marco2021-10-062021-10-062019Lam, Michael T., Coppola, Simona, Krumbach, Oliver H.F., et al.. "A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function." <i>Journal of Experimental Medicine,</i> 216, no. 12 (2019) Rockefeller University Press: 2778-2799. https://doi.org/10.1084/jem.20190147.https://hdl.handle.net/1911/111485Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.engThis article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 functionJournal articlejem_20190147https://doi.org/10.1084/jem.20190147