biostudies-literatureLam MTAssociazione Italiana per la Ricerca sul CancroFondazione Bambino GesùGerman Research FoundationItalian Ministry of HealthTelethonE-RareNIAID NIH HHSNHGRI NIH HHSNational Institutes of HealthNational Human Genome Research InstituteGerman Federal Ministry of Education and Research2778-2799https://www.ebi.ac.uk/biostudies/studies/S-EPMC6888978biostudies-literatureUnknown216(12)Hemophagocytic 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 <i>CDC42</i> mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. <i>CDC42</i> mutations had been associated with syndromic neurodevelopmental disorders. InThe Journal of experimental medicineA novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function.PMC6888978TGTUM1HG006542NSEuroNetR37 AI067946National Heart, Lung, and Blood InstituteAH 92/8-101GM1902CR01AI067946R01 AI067946R01 AI120989NET-2011-02350069IRTG 1902-P6EUROCIDUM1 HG006542IG21614R01AI120989-05Buchholzer MDiehl MChiriaco MPannone LGibbs RADe Benedetti FKrumbach OHFRosti VBrigida ICifaldi CPantaleoni FMace EMCao TNInsalaco AChinn IKAhmadian MRLupski JRBasso-Ricci LPutignani LBracaglia CCoban-Akdemir ZHPalma PFarina LCamerini SErichsen HCCarisey AFJanning PBryceson YTLevi Mortera SMessia VMerli PRamme KCancrini CNetter PJhangiani SNDvorsky RScala SDi Rocco MLocatelli FAiuti APrencipe GConti FCarsetti RTartaglia MMuzny DMMartinelli SHorne ANiceta MFinocchi ADi Cesare SCiolfi ATorralba-Raga LStray-Pedersen AOrange JSPastore ALam MTAkbarzadeh MCoppola SPascarella AZara EfalseA novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function.Hemophagocytic 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 <i>CDC42</i> mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. <i>CDC42</i> mutations had been associated with syndromic neurodevelopmental disorders. In2019-01-01T00:00:00Z2019 Dec2026-05-05T02:24:17.069Z2020-06-05T07:00:29ZS-EPMC68889783160167510.1084/jem.20190147