biostudies-literatureOleaga-Quintas CECOS-NORDNIAID NIH HHSANR-IFNGPHOXANR-HGDIFDNational Institutes of HealthNIH HHSANR-GENMSMD639-657https://www.ebi.ac.uk/biostudies/studies/S-EPMC8938944biostudies-literatureUnknown41(3)<h4>Purpose</h4>Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown.<h4>Methods</h4>We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives.<h4>Results</h4>We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mJournal of clinical immunologyInherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance.PMC8938944R01 AI095983ANR-14-CE15-006-01ANR13-ISV3-0001-01R37AI095983C19S01-63407ANR-16-CE17-0005-01R37 AI095983de Diego RPRestrepo JFLorenzo-Diaz LPuel AMartinez-Gallo MSajjath SMLopez-Herrera GLew DBJeziorski ERodriguez-Gallego CVogt GWitte TAbel LCasanova JLFernandez-Hidalgo NOleaga-Quintas CCondino-Neto ALaunay EBellanne-Chantelot CMonjo VCDonadieu JDeswarte CMendez NHSGuerin AGerceker BBustamante JRosain JRapaport FVigue MGLiu KThomas CMellouli FZhou YJLozano CRamirez KAMoncada-Velez MNeehus ALde Oliveira-Junior EBMartinez-Barricarte RO'Farrill Romanillos PCobat AMarot SLe Voyer TPasquet MColobran RCampos RACuffel AMarques LFieschi CArdeniz FOBranco LJobim MJobim LFAlejo NRBoisson-Dupuis SRoynard MVasconcelos JBerron-Ruiz LBrunel ASArias AAfalseInherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance.<h4>Purpose</h4>Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown.<h4>Methods</h4>We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives.<h4>Results</h4>We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had m2021-01-01T00:00:00Z2021 Apr2025-04-04T12:41:06.971Z2025-04-04T12:41:06.971ZS-EPMC89389443341708810.1007/s10875-020-00930-3