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

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dc.citation.firstpage2778
dc.citation.issueNumber12
dc.citation.journalTitleJournal of Experimental Medicine
dc.citation.lastpage2799
dc.citation.volumeNumber216
dc.contributor.authorLam, Michael T.
dc.contributor.authorCoppola, Simona
dc.contributor.authorKrumbach, Oliver H.F.
dc.contributor.authorPrencipe, Giusi
dc.contributor.authorInsalaco, Antonella
dc.contributor.authorCifaldi, Cristina
dc.contributor.authorBrigida, Immacolata
dc.contributor.authorZara, Erika
dc.contributor.authorScala, Serena
dc.contributor.authorDi Cesare, Silvia
dc.contributor.authorMartinelli, Simone
dc.contributor.authorDi Rocco, Martina
dc.contributor.authorPascarella, Antonia
dc.contributor.authorNiceta, Marcello
dc.contributor.authorPantaleoni, Francesca
dc.contributor.authorCiolfi, Andrea
dc.contributor.authorNetter, Petra
dc.contributor.authorCarisey, Alexandre F.
dc.contributor.authorDiehl, Michael
dc.contributor.authorAkbarzadeh, Mohammad
dc.contributor.authorConti, Francesca
dc.contributor.authorMerli, Pietro
dc.contributor.authorPastore, Anna
dc.contributor.authorLevi Mortera, Stefano
dc.contributor.authorCamerini, Serena
dc.contributor.authorFarina, Luciapia
dc.contributor.authorBuchholzer, Marcel
dc.contributor.authorPannone, Luca
dc.contributor.authorCao, Tram N.
dc.contributor.authorCoban-Akdemir, Zeynep H.
dc.contributor.authorJhangiani, Shalini N.
dc.contributor.authorMuzny, Donna M.
dc.contributor.authorGibbs, Richard A.
dc.contributor.authorBasso-Ricci, Luca
dc.contributor.authorChiriaco, Maria
dc.contributor.authorDvorsky, Radovan
dc.contributor.authorPutignani, Lorenza
dc.contributor.authorCarsetti, Rita
dc.contributor.authorJanning, Petra
dc.contributor.authorStray-Pedersen, Asbjorg
dc.contributor.authorErichsen, Hans Christian
dc.contributor.authorHorne, AnnaCarin
dc.contributor.authorBryceson, Yenan T.
dc.contributor.authorTorralba-Raga, Lamberto
dc.contributor.authorRamme, Kim
dc.contributor.authorRosti, Vittorio
dc.contributor.authorBracaglia, Claudia
dc.contributor.authorMessia, Virginia
dc.contributor.authorPalma, Paolo
dc.contributor.authorFinocchi, Andrea
dc.contributor.authorLocatelli, Franco
dc.contributor.authorChinn, Ivan K.
dc.contributor.authorLupski, James R.
dc.contributor.authorMace, Emily M.
dc.contributor.authorCancrini, Caterina
dc.contributor.authorAiuti, Alessandro
dc.contributor.authorAhmadian, Mohammad R.
dc.contributor.authorOrange, Jordan S.
dc.contributor.authorDe Benedetti, Fabrizio
dc.contributor.authorTartaglia, Marco
dc.date.accessioned2021-10-06T14:15:49Z
dc.date.available2021-10-06T14:15:49Z
dc.date.issued2019
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.
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.
dc.identifier.digitaljem_20190147
dc.identifier.doihttps://doi.org/10.1084/jem.20190147
dc.identifier.urihttps://hdl.handle.net/1911/111485
dc.language.isoeng
dc.publisherRockefeller University Press
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/).
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.titleA novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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