A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function

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dc.citation.firstpage2778en_US
dc.citation.issueNumber12en_US
dc.citation.journalTitleJournal of Experimental Medicineen_US
dc.citation.lastpage2799en_US
dc.citation.volumeNumber216en_US
dc.contributor.authorLam, Michael T.en_US
dc.contributor.authorCoppola, Simonaen_US
dc.contributor.authorKrumbach, Oliver H.F.en_US
dc.contributor.authorPrencipe, Giusien_US
dc.contributor.authorInsalaco, Antonellaen_US
dc.contributor.authorCifaldi, Cristinaen_US
dc.contributor.authorBrigida, Immacolataen_US
dc.contributor.authorZara, Erikaen_US
dc.contributor.authorScala, Serenaen_US
dc.contributor.authorDi Cesare, Silviaen_US
dc.contributor.authorMartinelli, Simoneen_US
dc.contributor.authorDi Rocco, Martinaen_US
dc.contributor.authorPascarella, Antoniaen_US
dc.contributor.authorNiceta, Marcelloen_US
dc.contributor.authorPantaleoni, Francescaen_US
dc.contributor.authorCiolfi, Andreaen_US
dc.contributor.authorNetter, Petraen_US
dc.contributor.authorCarisey, Alexandre F.en_US
dc.contributor.authorDiehl, Michaelen_US
dc.contributor.authorAkbarzadeh, Mohammaden_US
dc.contributor.authorConti, Francescaen_US
dc.contributor.authorMerli, Pietroen_US
dc.contributor.authorPastore, Annaen_US
dc.contributor.authorLevi Mortera, Stefanoen_US
dc.contributor.authorCamerini, Serenaen_US
dc.contributor.authorFarina, Luciapiaen_US
dc.contributor.authorBuchholzer, Marcelen_US
dc.contributor.authorPannone, Lucaen_US
dc.contributor.authorCao, Tram N.en_US
dc.contributor.authorCoban-Akdemir, Zeynep H.en_US
dc.contributor.authorJhangiani, Shalini N.en_US
dc.contributor.authorMuzny, Donna M.en_US
dc.contributor.authorGibbs, Richard A.en_US
dc.contributor.authorBasso-Ricci, Lucaen_US
dc.contributor.authorChiriaco, Mariaen_US
dc.contributor.authorDvorsky, Radovanen_US
dc.contributor.authorPutignani, Lorenzaen_US
dc.contributor.authorCarsetti, Ritaen_US
dc.contributor.authorJanning, Petraen_US
dc.contributor.authorStray-Pedersen, Asbjorgen_US
dc.contributor.authorErichsen, Hans Christianen_US
dc.contributor.authorHorne, AnnaCarinen_US
dc.contributor.authorBryceson, Yenan T.en_US
dc.contributor.authorTorralba-Raga, Lambertoen_US
dc.contributor.authorRamme, Kimen_US
dc.contributor.authorRosti, Vittorioen_US
dc.contributor.authorBracaglia, Claudiaen_US
dc.contributor.authorMessia, Virginiaen_US
dc.contributor.authorPalma, Paoloen_US
dc.contributor.authorFinocchi, Andreaen_US
dc.contributor.authorLocatelli, Francoen_US
dc.contributor.authorChinn, Ivan K.en_US
dc.contributor.authorLupski, James R.en_US
dc.contributor.authorMace, Emily M.en_US
dc.contributor.authorCancrini, Caterinaen_US
dc.contributor.authorAiuti, Alessandroen_US
dc.contributor.authorAhmadian, Mohammad R.en_US
dc.contributor.authorOrange, Jordan S.en_US
dc.contributor.authorDe Benedetti, Fabrizioen_US
dc.contributor.authorTartaglia, Marcoen_US
dc.date.accessioned2021-10-06T14:15:49Zen_US
dc.date.available2021-10-06T14:15:49Zen_US
dc.date.issued2019en_US
dc.description.abstractHemophagocytic 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.en_US
dc.identifier.citationLam, 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.en_US
dc.identifier.digitaljem_20190147en_US
dc.identifier.doihttps://doi.org/10.1084/jem.20190147en_US
dc.identifier.urihttps://hdl.handle.net/1911/111485en_US
dc.language.isoengen_US
dc.publisherRockefeller University Pressen_US
dc.rightsThis 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/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.titleA novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 functionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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