biostudies-literatureMohajeri AThe University of British Columbia Four Year Doctoral FellowshipNational Institutes of HealthTier 1 Canada Research Chair in Pediatric Precision HealthCanadian Institutes of Health ResearchVanier Canada Graduate ScholarshipAubrey J. Tingle Professor of Pediatric ImmunologyOffice of Strategic Coordination/Office of the NIH Director under AwardHealth Professional-Investigator award from Michael Smith Health Research BCNHGRI NIH HHSJeffrey Modell FoundationGenome British ColumbiaGenome CanadaBC Children’s Hospital Research InstituteProvidence Healthcare Research Institute Early Career Investigator award1092-1104https://www.ebi.ac.uk/biostudies/studies/S-EPMC11206234biostudies-literatureUnknown60(11)<h4>Background</h4>Helios (encoded by <i>IKZF2</i>), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognised for its role in the development and function of T lymphocytes, particularly the CD4⁺ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans.<h4>Methods</h4>We performed detailed phenotypic, genomic and functional investigations on two unrelated individuals with a phenotype of immune dysregulation comJournal of medical geneticsDominant negative variants in <i>IKZF2</i> cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.PMC11206234F32 HG000130PJT 178054F17-04161U01 HG007709U01HG007709Dasari SLin SArmstrong LUndiagnosed Diseases NetworkLiu XZEmrick LTSolem EWener MNovacic DHalparin JCare4Rare Canada ConsortiumWorley KSutton SDon Hadley SHCunningham MAmendola LButte MJJobanputra VWalker MStoler JMJean-Marie OLawrence Merritt JBonner DKozuira MWorley KCCooper CMLoo SKSmith ECCoakley TRPalmer CGFieg ELPapp JCBellen HJAcosta MTSessions Cole FKozak FKPosey JELanza IRvan Karnebeek CSalman ASilverman EKRahmanian RForghani IDayal JGJarvik GPVogel TPAdams DRDuncan LKrakow DByers PMartin MGBale JFisher PGFogel BLMahoney RRenteria GSinsheimer JSLanpher BCScott DAIzumi KMcCray ATWhitlock JNewman JHChang TPSweetser DAAdam MAlvey JTran AAGochuico BMacnamara EFCarrasquillo OCobban LANickerson DBerg-Rood BRaper ADavis JHildebrand KJMarth GCogan JDSchaechter JWang LKNicholas SKBivona STabor HKWenger TBejerano GMulvihill JJarvik JCraigen WJMight MSharma MBoyd BKennedy JIsasi RWangler MFKaraviti LPak SZuchner SBayrak-Toydemir PHisama FMMartin BAHenkelman EHayes NLongo NKetkar SRosenfeld JAJamal FMao RLiu PSullivan KMamounas LAWallace SWambach JLalani SRAlvarez RLDorrani NParker NHBlue ESaporta MOrengo JPThorson WTelischi FWheeler MTHing AHorike-Pyne MDel Bel KLMartinez-Agosto JABennett JKilich GBamshad MCorona RZhang ZTekin MEng CMD'Souza PHom JKravets ECarl Pallais JNelson SFWaqas MHalley MCSmith KSSybert VIntrone WKrasnewich DMBohnsack JUrv TKTifft CJWan JBaldridge DLewis RAHolm IASacco RSolomon BSolnica-Krezel LBiggs CMClark GDMcCauley JRodan LHSababi Azamian MByrd WEKohane ISNieves-Rodriguez SBeck AMoretti PPotocki LGrajewski ACrouse ABGlass ILehman AWegner DDoss ALRon Scott CHutchison SRives LCoggins MAndrews AKiley DKohler JNShashi VBehrens EBotto LAshley EABacino CAChanprasert SEckstein DJBarbouth DYang GXBriere LCQuinlan AMalicdan MVRuzhnikov MMohajeri AMaravilla KBeggs AHMarwaha SNakano-Okuno MHamid RReuter CMXiao CDai HSpillmann RCGoddard PCSisco KSun AVanderver ABalasubramanyam ABurrage LCShin JBrown GSchoch KMarom RUngar RAManolio TAToro CPace LLee BHCassini TChao HTHuang AOglesbee DPuseySwerdzewski BNVelinder MYang JMcConkie-Rosell AMorava EMaduro VVYamamoto SViskochil DCarey JSampson JBLu HLevitt RBademci GFalk MHigh FBernstein JABerry GTMostafavi STurvey SEBican ABurke EABrokamp EKobren SNYang CLLam BLeBlanc KLam CRossignol FWalley NMRobertson AKHassey KTan ALCope HWard PAEarl DMcGee EMacRae CAHubshman MWMefford HSullivan JADoherty DMirzaa GPhillipsIII JARosenwasser NVaseghi-Shanjani MMaas RLColley HAGahl WALoscalzo JSchedl TJayadev SRao DADipple KWolfe LAKorrick SRaskind WDell'Angelica ECGodfrey RATan QKWesterfield MDouine EDWahl CEGolden-Grant KfalseDominant negative variants in <i>IKZF2</i> cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.<h4>Background</h4>Helios (encoded by <i>IKZF2</i>), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognised for its role in the development and function of T lymphocytes, particularly the CD4⁺ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans.<h4>Methods</h4>We performed detailed phenotypic, genomic and functional investigations on two unrelated individuals with a phenotype of immune dysregulation com2023-01-01T00:00:00Z2023 Nov2026-04-29T23:17:24.479Z2026-04-07T15:37:15.198ZS-EPMC112062343731618910.1136/jmg-2022-109127