{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T18:41:52Z","timestamp":1793990512268,"version":"4.8.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>GATA2 deficiency is a disease with a broad spectrum of clinical presentation, ranging from lymphedema, deafness, pulmonary dysfunction to miscarriage and urogenital anomalies, but it is mainly recognized as an immune system and bone marrow disorder. It is caused by various heterozygous mutations in the <jats:italic>GATA2<\/jats:italic> gene, encoding for a zinc finger transcription factor with a key role for the development and maintenance of a pool of hematopoietic stem cells; notably, most of these mutations arise <jats:italic>de novo<\/jats:italic>. Patients carrying a mutated allele usually develop a loss of some cell populations, such as B-cell, dendritic cell, natural killer cell, and monocytes, and are predisposed to disseminated human papilloma virus and mycobacterial infections. Also, these patients have a predisposition to myeloid neoplasms, including myelodysplastic syndromes, myeloproliferative neoplasms, chronic myelomonocytic leukaemia. The age of symptoms onset can vary greatly even also within the same family, ranging from early childhood to late adulthood; incidence increases by age and most frequently clinical presentation is between the second and third decade of life. Currently, haematopoietic stem cell transplantation represents the only curative treatment, restoring both the hematopoietic and immune system function.<\/jats:p>","DOI":"10.3389\/fimmu.2022.865773","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T04:22:38Z","timestamp":1655094158000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["GATA 2 Deficiency: Focus on Immune System Impairment"],"prefix":"10.3389","volume":"13","author":[{"given":"Francesco","family":"Fabozzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Mastronuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ceglie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Masetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Leardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-687889","article-title":"GATA Factor Mutations in Hematologic Disease","volume":"129","author":"Crispino","year":"2017","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.923","article-title":"Mutations in GATA2 Cause Primary Lymphedema Associated With a Predisposition to Acute Myeloid Leukemia (Emberger Syndrome)","volume":"43","author":"Ostergaard","year":"2011","journal-title":"Nat Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-356352","article-title":"Mutations in GATA2 are Associated With the Autosomal Dominant and Sporadic Monocytopenia and Mycobacterial Infection (MonoMAC) Syndrome","volume":"118","author":"Hsu","year":"2011","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.913","article-title":"Heritable GATA2 Mutations Associated With Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia","volume":"43","author":"Hahn","year":"2011","journal-title":"Nat Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-360313","article-title":"Exome Sequencing Identifies GATA-2 Mutation as the Cause of Dendritic Cell, Monocyte, B and NK Lymphoid Deficiency","volume":"118","author":"Dickinson","year":"2011","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198906293202605","article-title":"Severe Herpesvirus Infections in an Adolescent Without Natural Killer Cells","volume":"320","author":"Biron","year":"1989","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-453969","article-title":"Mutations in GATA2 Cause Human NK Cell Deficiency With Specific Loss of the CD56bright Subset","volume":"121","author":"Mace","year":"2013","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2204","article-title":"GATA2 Mutations in Myeloid Malignancies: Two Zinc Fingers in Many Pies","volume":"72","author":"Leubolt","year":"2020","journal-title":"IUBMB Life"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2021.101278","article-title":"GATA2 and Marrow Failure","volume":"34","author":"Fabozzi","year":"2021","journal-title":"Best Pract Res Clin Haematol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13317","article-title":"Haematopoietic and Immune Defects Associated With GATA2 Mutation","volume":"169","author":"Collin","year":"2015","journal-title":"Br J Haematol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2017.05.002","article-title":"GATA2 Deficiency and Related Myeloid Neoplasms","volume":"54","author":"Wlodarski","year":"2017","journal-title":"Semin Hematol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/371221a0","article-title":"An Early Haematopoietic Defect in Mice Lacking the Transcription Factor GATA-2","volume":"371","author":"Tsai","year":"1994","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61623","article-title":"Cis-Element Mutated in GATA2-Dependent Immunodeficiency Governs Hematopoiesis and Vascular Integrity","volume":"122","author":"Johnson","year":"2012","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-2989","article-title":"Haploinsufficiency of GATA-2 Perturbs Adult Hematopoietic Stem-Cell Homeostasis","volume":"106","author":"Rodrigues","year":"2005","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2007.01158.x","article-title":"Reduced BMP4 Abundance in Gata2 Hypomorphic Mutant Mice Result in Uropathies Resembling Human CAKUT","volume":"13","author":"Hoshino","year":"2008","journal-title":"Genes Cells"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2188","article-title":"Quantitative and Qualitative Impairments in GATA2 and Myeloid Neoplasms","volume":"72","author":"Shimizu","year":"2020","journal-title":"IUBMB Life"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13959","article-title":"GATA2 Hypomorphism Induces Chronic Myelomonocytic Leukemia in Mice","volume":"110","author":"Harada","year":"2019","journal-title":"Cancer Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/s42003-022-03316-w","article-title":"Heterozygous Variants in GATA2 Contribute to DCML Deficiency in Mice by Disrupting Tandem Protein Binding","volume":"5","author":"Hasegawa","year":"2022","journal-title":"Commun Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24271","article-title":"GATA2 Deficiency Syndrome: A Decade of Discovery","volume":"42","author":"Homan","year":"2021","journal-title":"Hum Mutat"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2020.101197","article-title":"Germline Predisposition in Myeloid Neoplasms: Unique Genetic and Clinical Features of GATA2 Deficiency and SAMD9\/SAMD9L Syndromes","volume":"33","author":"Sahoo","year":"2020","journal-title":"Best Pract Res Clin Haematol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0899-5","article-title":"Synonymous GATA2 Mutations Result in Selective Loss of Mutated RNA and are Common in Patients With GATA2 Deficiency","volume":"34","author":"Kozyra","year":"2020","journal-title":"Leukemia"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005217","article-title":"GATA2 Deficiency Phenotype Associated With Tandem Duplication GATA2 and Over-Expression of GATA2-As1","author":"Singh","year":"2021","journal-title":"Blood Adv"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.181909","article-title":"Natural History of GATA2 Deficiency in a Survey of 79 French and Belgian Patients","volume":"103","author":"Donadieu","year":"2018","journal-title":"Haematologica"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12559","article-title":"Mutations of the GATA2 and CEBPA Genes in Paediatric Acute Myeloid Leukaemia","volume":"164","author":"Shiba","year":"2014","journal-title":"Br J Haematol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002953","article-title":"Human GATA2 Mutations and Hematologic Disease: How Many Paths to Pathogenesis","volume":"4","author":"Bresnick","year":"2020","journal-title":"Blood Adv"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0134-9","article-title":"GATA2 Monoallelic Expression Underlies Reduced Penetrance in Inherited GATA2 -Mutated MDS\/AML","volume":"32","author":"Al Seraihi","year":"2018","journal-title":"Leukemia"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1516039","article-title":"Monozygotic Twins With Shared De Novo GATA2 Mutation But Dissimilar Phenotypes Due to Differential Promoter Methylation","volume":"60","author":"Kim","year":"2019","journal-title":"Leuk Lymphoma"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-515528","article-title":"GATA2 Deficiency: A Protean Disorder of Hematopoiesis, Lymphatics, and Immunity","volume":"123","author":"Spinner","year":"2014","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-517151","article-title":"The Evolution of Cellular Deficiency in GATA2 Mutation","volume":"123","author":"Dickinson","year":"2014","journal-title":"Blood"},{"key":"B30","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s10875-020-00758-x","article-title":"Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification","volume":"40","author":"Bousfiha","year":"2020","journal-title":"J Clin Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00089-4","article-title":"Host Susceptibility to Non-Tuberculous Mycobacterial Infections","volume":"15","author":"Wu","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2021.05.046","article-title":"Pulmonary Manifestations of GATA2 Deficiency","volume":"160","author":"Marciano","year":"2021","journal-title":"Chest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101459","article-title":"The Human Syndrome of Dendritic Cell, Monocyte, B and NK Lymphoid Deficiency","volume":"208","author":"Bigley","year":"2011","journal-title":"J Exp Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.5MA0815-388R","article-title":"Altered Chemotactic Response to CXCL12 in Patients Carrying GATA2 Mutations","volume":"99","author":"Maciejewski-Duval","year":"2016","journal-title":"J Leukoc Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-012-9400-3","article-title":"The Inverted CD4\/CD8 Ratio and Associated Parameters in 66-Year-Old Individuals: The Swedish HEXA Immune Study","volume":"35","author":"Strindhall","year":"2013","journal-title":"Age (Dordr)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.07.049","article-title":"Warts and All: Human Papillomavirus in Primary Immunodeficiencies","volume":"130","author":"Leiding","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01869","article-title":"GATA2 Deficiency and Epstein\u2013Barr Virus Disease","volume":"8","author":"Cohen","year":"2017","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"8305","DOI":"10.1038\/s41598-020-64852-1","article-title":"A Panoply of Rheumatological Manifestations in Patients With GATA2 Deficiency","volume":"10","author":"Amarnani","year":"2020","journal-title":"Sci Rep"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-018-3472-9","article-title":"Autoimmune Manifestations Associated With Myelodysplastic Syndromes","volume":"97","author":"Grignano","year":"2018","journal-title":"Ann Hematol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13071532","article-title":"Autoimmune Complications in Hematologic Neoplasms","volume":"13","author":"Barcellini","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12102962","article-title":"GATA2 Related Conditions and Predisposition to Pediatric Myelodysplastic Syndromes","volume":"12","author":"Bruzzese","year":"2020","journal-title":"Cancers"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000126","article-title":"GATA2 Deficiency","volume":"15","author":"Hsu","year":"2015","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.090217","article-title":"Acquired ASXL1 Mutations are Common in Patients With Inherited GATA2 Mutations and Correlate With Myeloid Transformation","volume":"99","author":"West","year":"2014","journal-title":"Haematologica"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-669937","article-title":"Prevalence, Clinical Characteristics, and Prognosis of GATA2-Related Myelodysplastic Syndromes in Children and Adolescents","volume":"127","author":"Wlodarski","year":"2016","journal-title":"Blood"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01511-6","article-title":"Clinical Evolution, Genetic Landscape and Trajectories of Clonal Hematopoiesis in SAMD9\/SAMD9L Syndromes","volume":"27","author":"Sahoo","year":"2021","journal-title":"Nat Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-021-01374-y","article-title":"Hematopoietic Stem Cell Transplantation in Children and Adolescents With GATA2-Related Myelodysplastic Syndrome","volume":"56","author":"Bortnick","year":"2021","journal-title":"Bone Marrow Transplant"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-374363","article-title":"Loss-Of-Function Germline GATA2 Mutations in Patients With MDS\/AML or MonoMAC Syndrome and Primary Lymphedema Reveal a Key Role for GATA2 in the Lymphatic Vasculature","volume":"119","author":"Kazenwadel","year":"2012","journal-title":"Blood"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22373","article-title":"Gata2 is Required for the Development of Inner Ear Semicircular Ducts and the Surrounding Perilymphatic Space","volume":"239","author":"Haugas","year":"2010","journal-title":"Dev Dynamics"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13433","article-title":"Uterinenatural Killer Cells and Recurrent Spontaneous Abortion","author":"Fu","year":"2021","journal-title":"Am J Reprod Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2018.04.004","article-title":"Germline GATA2 Mutation and Bone Marrow Failure","volume":"32","author":"McReynolds","year":"2018","journal-title":"Hematology\/Oncol Clinics North America"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17840","article-title":"Donor Source and Post-Transplantation Cyclophosphamide Influence Outcome in Allogeneic Stem Cell Transplantation for GATA2 Deficiency","volume":"196","author":"Nichols-Vinueza","year":"2022","journal-title":"Br J Haematol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR-Cas9 Gene Editing for Sickle Cell Disease and \u03b2-Thalassemia","volume":"384","author":"Frangoul","year":"2021","journal-title":"N Engl J Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fgeed.2020.602182","article-title":"From Basic Biology to Patient Mutational Spectra of GATA2 Haploinsufficiencies: What Are the Mechanisms, Hurdles, and Prospects of Genome Editing for Treatment","volume":"2","author":"Koyunlar","year":"2020","journal-title":"Front Genome Ed"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005538","article-title":"Somatic Genetic Rescue in Hematopoietic Cells in GATA2 Deficiency","volume":"136","author":"Catto","year":"2020","journal-title":"Blood"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007001","article-title":"Natural Gene Therapy in Hematopoietic Disorders: GATA Too","volume":"136","author":"Jongmans","year":"2020","journal-title":"Blood"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.865773\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T04:22:41Z","timestamp":1655094161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.865773\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,13]]},"references-count":55,"alternative-id":["10.3389\/fimmu.2022.865773"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.865773","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,13]]},"article-number":"865773"}}