{"paper_id":"0c305518-a6f1-436c-9dd2-2f6b93050f78","body_text":"GATA2 deficiency with early-onset interstitial pneumonia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report GATA2 deficiency with early-onset interstitial pneumonia Yuriko Sugiura, Takahiro Ando, Hirokazu Urushiyama, Akihisa Mitani, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4090026/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background GATA 2 deficiency is a rare disease caused by a germline heterozygous mutation in the GATA 2 gene. This mutation is known to cause a decrease in hematopoietic stem cells and a decrease in monocytes, dendritic cells, NK cells, and B cells, leading to various diseases such as hematological, infectious, and respiratory diseases. Case presentation: In this study, we present a case in which a patient in her 20s developed sensorineural hearing loss, schizophrenia, and interstitial pneumonia, leading to the diagnosis of GATA 2 deficiency. The patient later developed pulmonary hypertension as the interstitial pneumonia progressed. Conclusions Early-onset interstitial pneumonia may be a rare phenotype of GATA 2 deficiency. GATA2 deficiency interstitial pneumonia hearing loss Figures Figure 1 Background GATA 2 deficiency is an autosomal dominant inheritance disorder caused by heterozygous mutations in the GATA 2 gene 1) . GATA 2 is a transcription factor, binding to promoter/enhancer regions of target genes to regulate hematopoietic stem cell proliferation, embryonic development, and vascularization.STT Pathogenic GATA 2 mutations cause haploinsufficiency 2)3) and is reported to cause a variety of diseases, including hematologic neoplasms, immunodeficiency, autoimmune diseases, lung diseases, and neurological diseases. The most common pulmonary diseases are alveolar proteinosis, recurrent respiratory tract infections, and pulmonary hypertension 4) . Only one case 5) of interstitial pneumonia has been reported to complicate GATA 2 deficiency. In this report, we describe a case of GATA 2 deficiency with early-onset interstitial pneumonia. Case presentation A 41-year-old woman had a history of recurrent otitis media and infections since childhood, candida esophagitis at age 16, and aseptic meningitis at age 17. Her mother has a history of recurrent infections, tuberculosis, Wegener's granulomatosis, and died of hematologic disease at age 45. Her father has a history of mental illness (schizophrenia, bipolar affective disorder, autism) and died of cardiac disease at age 65. She had no siblings. At age 23, she was diagnosed with interstitial pneumonia. At the same time, she was diagnosed with schizophrenia and mental retardation. At age 24, she developed sensorineural hearing loss. Bronchoscopy was performed to investigate the cause of interstitial pneumonia. Bronchoalveolar lavage showed no abnormal findings, and transbronchial lung biopsy showed thickening and fibrosis of the alveolar septum (Supplementary Fig. 1). Pathological examination was negative result for alveolar proteinosis. At age of 26, she was referred to our hospital for further examination and treatment, but the cause of interstitial pneumonia was not found (Fig. 1 a). At age of 28 years, erythema nodosum appeared. When she was hospitalized for aseptic meningitis at age of 28, her laboratory data revealed a white blood cell count of 2.7x10 3 /µL (neutrophil count 1.8x10 3 /µL, monocyte count 0 /µL, lymphocyte count 300 /µL), T cell count 243 /µL (82%) and B cell count 11 /µL (4%), indicating a decreased B cell count and decreased B and T cell neoplastic capacity. IgG was normal at 1124 mg/dL. However, no causative disease was identified. The immunodeficiency was suspected, but the definitive diagnosis was not reached. After continued follow-up, at age 37, exome analysis revealed Chr3(GRCh37):g128200721G > A, NM_001145661.2:c.1084C > T, p.R362*, leading to a diagnosis of heterozygous nonsense variant GATA 2 deficiency. At this time, her white blood cell count was 5.1 x 10 3 /µl (neutrophil count 4.3 x 10 3 /µl, monocyte count 0 /µl, lymphocyte count 600 /µl) and IgG was 3,905 mg/dl. Interstitial pneumonia had progressed gradually (Fig. 1 B). At age of 41, she was admitted to the hospital due to respiratory failure and exacerbation of heart failure, and cardiac ultrasonography showed elevated right ventricular systolic pressure (48 mmHg) suggestive of pulmonary hypertension. During the 15 years between referral and present, interlobular septal wall thickening with ground-glass and granular shadows worsened, KL-6 increased from 836 U/mL to 3341 U/ml and forced vital capacity decreased from 2.47 L to 1.29 L. IgG, which was normal at the age of 28, increased and reached 5350 mg/dL. Recent complete blood count showed white blood cells 4.5 x 10 3 /µl (neutrophils 3.3 x 10 3 /µl, lymphocytes 9.8 x 10 2 /µl, monocytes 41/µl, eosinophil 162/µl, basophil 18/µl ). Flow cytometry results showed a decrease in B cells and effector memory T cells, follicular helper T cells, natural killer cells and natural killer T cells while dendric cells were deficient. CD3 positive T cells and helper T cells were relatively increased (Table 1 ). Currently, she requires home oxygen therapy due to the progression of interstitial pneumonia (Fig. 1 c) and pulmonary hypertension. Since she had schizophrenia, bone marrow transplant was not indicated, and a bone marrow biopsy has not been performed. Table 1 the result of flow cytometry. CD19 + CD20+ 0.76% ** CD20 + CD21+ 0.46% CD20 + CD21- 0.32% * CD19 + CD27+ 0.80% CD19 + CD27- 0.26% CD3+ 93.1% CD4+ 50.1% CD45RO+ 39.9% CXCR5+ (follicular helper T) 6.89% ** CCR6 + CXCR3+ (Th1star) 23.8% * CD45RO- 15.0% CD45RA + CD31+(recent thymic emigrant) 64.5% CD45RA + CD31-(上記以外) 35.5% * CD62L + CCR7+ (central memory) 73.0% CD62L-CCR7- (effector memory) 11.5% ** Th1, Th2, Th17, Treg normal CD8+ 45.0% CD45RO+ 23.4% CD45RO- 25.7% Va24 + Vb11+ (NKT cell) 0.002% ** CD16 + CD56+ 1.20% ** Lineage- HLADR + CD123+ (plasmacytoid DC) almost 0% ** Lineage- HLADR + CD11c+ (classic DC) almost 0% ** * indicates abnormal high value. ** indicate abnormal low value. Discussion and Conclusions Many mutations have been detected in the GATA2 gene, and mutations related to diseases are most often in one of the two zinc finger-binding domains 4) . In this case, the GATA2 mutation was found within the domain of zinc finger II. GATA 2 gene mutations are known to cause haploinsufficiency 2)3) , which lead to various phenotypic diseases. GATA 2 is a zinc finger transcription factor necessary for differentiation of endothelial and immature hematopoietic cells 6) . GATA 2 is known to promote macrophage differentiation. 7)8) Alveolar macrophage dysfunction in GATA 2 deficiency and recurrent infection lead to damage of lung elastin, which also may contribute to the pulmonary changes seen in patients with GATA 2 deficiency. 9)10) The GATA 2 gene plays a functional role in the maintenance of helical ganglion cells and hearing ability, and its loss may result in hearing loss. 11) In a cohort study of pediatric MDS patients with GATA 2 deficiency, it was reported that 9% of patients presented with hearing loss. 12) Association of psychiatric disease with GATA 2 deficiency is unknown; 19% of pediatric MDS patients with GATA 2 deficiency included behavioral problems such as autism and aggressive behavior, and neurological symptoms were seen in 8 of 484 patients with GATA 2 deficiency 4)12) In the present case, the patient developed recurrent infection, sensorineural hearing loss, and erythema nodosum, all known manifestations of GATA 2 deficiency 13) , although no hematological malignancy developed. Based on the family history, it is likely that her mother had GATA 2 deficiency, and she may have been genetically predisposed to schizophrenia from her father, not her mother. Therefore, the association between schizophrenia and GATA 2 deficiency was unclear. The patient's history of repeated infections since childhood led us to suspect primary immunodeficiency, which led to the diagnosis of GATA 2 deficiency. Flow cytometry of peripheral blood showed abnormalities in the composition of lymphocytes and that dendric cells were deficient. It has been reported that GATA 2 patients with MDS showed severe peripheral blood monocytopenia and B cell and NK cell lymphopenia, which is similar to what we have seen. 14) Little has been reported on peripheral blood flow cytometry in GATA 2-deficient patients without hematological disease. Pulmonary diseases known to be associated with GATA 2 deficiency include pulmonary alveolar proteinosis (PAP), pulmonary hypertension (PH), and non-tuberculous mycobacterial infection. PAP and PH have been reported to occur in 9% and 7% of patients with GATA 2 deficiency, respectively 4) . On the other hand, there is only one case report of GATA 2 deficiency with interstitial pneumonia 5) . In our present case, there was no evidence of PAP from bronchoscopy. She had no medications at her first visit to our clinic, and based on the clinical course and laboratory results, it is highly unlikely that she had drug-induced interstitial pneumonia or collagen-related interstitial pneumonia. As interstitial pneumonia progressed on chest CT, development of PAP could not be completely ruled out. Pulmonary hypertension was also observed, which considered an element of both GATA 2 deficiency and/or the presence of lung disease (i.e., World Health Organization Group 3 and/or Group 5). In conclusion, we present a patient with recurrent infections who in her 20s developed interstitial pneumonia and sensorineural hearing loss, leading to the diagnosis of GATA 2 deficiency. Early-onset interstitial pneumonia may be a rare phenotype of GATA 2 deficiency. Abbreviations PAP pulmonary alveolar proteinosis PH pulmonary hypertension Declarations Funding None of the authors have funding to declare. Data availability Data and materials are available from the corresponding author upon request. Consent for publication Written informed consent for publication of the patient’s clinical information and images were obtained by the patients. Author contribution: YS collected clinical data and wrote the manuscript. TA, HU, AM, and GT contributed clinical data, reviewed, and edited the manuscript. KK and TM provided genetic information and conducted FACS analysis. HK came up with the study concept, contributed clinical data, and edited the manuscript. All authors approved the final version of the manuscript for publication. Competing interests : The authors declare that they have no competing interests. Acknowledgements: Not applicable References Xabier Cortes-Lavaud et al. GATA2 germline mutations impair GATA2 transcription, causing haploinsufficiency: functional analysis of the p.Arg396Gln mutation J Immunol (2015) 194 (5): 2190–2198. Michael A et al. GATA 2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood, 2014; 123(6): 809–821 Amy P et al. GATA 2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome. Blood, 2013; 121(19): 3830–3837 Beatriz E Marciano et al. Pulmonary Manifestations of GATA 2 Deficiency. CHEST 2021;160(4):1350–1359 Tamara S et al. Diffuse parenchymal lung disease as first clinical manifestation of GATA -2 deficiency in childhood. BMC Pulmonary Medicine 2015 Feb 10; 15:8 Cohen JI (2017) GATA2 Deficiency and Epstein–Barr Virus Disease. Front. Immunol. 8:1869. doi: 10.3389/fimmu.2017.01869 Kenji K et al. Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA -2. Blood. 2006; 107: 1857–1863 Neil P et al. GATA -2 regulates granulocyte-macrophage progenitor cell function. Blood. 2008; 112: 4862–4873 Tang X et al. Down-regulation of GATA -2 transcription during Pneumocystis carinii infection. Infect Immun. 2000; 68: 4720–4724 Mark E Lasbury et al. Effect of transcription factor GATA -2 on phagocytic activity of alveolar macrophages from Pneumocystis carinii-infected hosts. Infect Immun. 2003; 71: 4943–4952 Tomofumi Hoshino et al. Spiral ganglion cell degeneration-induced deafness as a consequence of reduced GATA factor activity. Genes to Cells 2019; 24(8):534–545 Marcin W Wlodarski et al. Prevalence, clinical characteristic, and prognosis of GATA 2-related myelodysplastic syndromes in children and adolescents. CME 2016; 127(11):1387–1397 Claire C et al. GATA 2 deficiency syndrome; A decade of discovery. Human Mutation 2021; 42(11): 1365–1517 Karthik A Ganapathi et al. GATA 2 deficiency-associated bone marrow disorder differs from idiopathic asplastic anemia. Blood 2015; 125(1):56–70 Additional Declarations No competing interests reported. Supplementary Files GATA2deficiencysuppelementary.pptx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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pneumonia\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003e \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency is an autosomal dominant inheritance disorder caused by heterozygous mutations in the \\u003cem\\u003eGATA\\u003c/em\\u003e2 gene\\u003csup\\u003e1)\\u003c/sup\\u003e. \\u003cem\\u003eGATA\\u003c/em\\u003e2 is a transcription factor, binding to promoter/enhancer regions of target genes to regulate hematopoietic stem cell proliferation, embryonic development, and vascularization.STT Pathogenic \\u003cem\\u003eGATA\\u003c/em\\u003e2 mutations cause haploinsufficiency \\u003csup\\u003e2)3)\\u003c/sup\\u003e and is reported to cause a variety of diseases, including hematologic neoplasms, immunodeficiency, autoimmune diseases, lung diseases, and neurological diseases. The most common pulmonary diseases are alveolar proteinosis, recurrent respiratory tract infections, and pulmonary hypertension\\u003csup\\u003e4)\\u003c/sup\\u003e. Only one case\\u003csup\\u003e5)\\u003c/sup\\u003e of interstitial pneumonia has been reported to complicate \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency. In this report, we describe a case of \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency with early-onset interstitial pneumonia.\\u003c/p\\u003e\"},{\"header\":\"Case presentation\",\"content\":\"\\u003cp\\u003eA 41-year-old woman had a history of recurrent otitis media and infections since childhood, candida esophagitis at age 16, and aseptic meningitis at age 17. Her mother has a history of recurrent infections, tuberculosis, Wegener's granulomatosis, and died of hematologic disease at age 45. Her father has a history of mental illness (schizophrenia, bipolar affective disorder, autism) and died of cardiac disease at age 65. She had no siblings. At age 23, she was diagnosed with interstitial pneumonia. At the same time, she was diagnosed with schizophrenia and mental retardation. At age 24, she developed sensorineural hearing loss. Bronchoscopy was performed to investigate the cause of interstitial pneumonia. Bronchoalveolar lavage showed no abnormal findings, and transbronchial lung biopsy showed thickening and fibrosis of the alveolar septum (Supplementary Fig.\\u0026nbsp;1). Pathological examination was negative result for alveolar proteinosis. At age of 26, she was referred to our hospital for further examination and treatment, but the cause of interstitial pneumonia was not found (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ea). At age of 28 years, erythema nodosum appeared. When she was hospitalized for aseptic meningitis at age of 28, her laboratory data revealed a white blood cell count of 2.7x10\\u003csup\\u003e3\\u003c/sup\\u003e /\\u0026micro;L (neutrophil count 1.8x10\\u003csup\\u003e3\\u003c/sup\\u003e /\\u0026micro;L, monocyte count 0 /\\u0026micro;L, lymphocyte count 300 /\\u0026micro;L), T cell count 243 /\\u0026micro;L (82%) and B cell count 11 /\\u0026micro;L (4%), indicating a decreased B cell count and decreased B and T cell neoplastic capacity. IgG was normal at 1124 mg/dL. However, no causative disease was identified. The immunodeficiency was suspected, but the definitive diagnosis was not reached. After continued follow-up, at age 37, exome analysis revealed Chr3(GRCh37):g128200721G\\u0026thinsp;\\u0026gt;\\u0026thinsp;A, NM_001145661.2:c.1084C\\u0026thinsp;\\u0026gt;\\u0026thinsp;T, p.R362*, leading to a diagnosis of heterozygous nonsense variant \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency. At this time, her white blood cell count was 5.1 x 10\\u003csup\\u003e3\\u003c/sup\\u003e /\\u0026micro;l (neutrophil count 4.3 x 10\\u003csup\\u003e3\\u003c/sup\\u003e /\\u0026micro;l, monocyte count 0 /\\u0026micro;l, lymphocyte count 600 /\\u0026micro;l) and IgG was 3,905 mg/dl. Interstitial pneumonia had progressed gradually (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003eB). At age of 41, she was admitted to the hospital due to respiratory failure and exacerbation of heart failure, and cardiac ultrasonography showed elevated right ventricular systolic pressure (48 mmHg) suggestive of pulmonary hypertension. During the 15 years between referral and present, interlobular septal wall thickening with ground-glass and granular shadows worsened, KL-6 increased from 836 U/mL to 3341 U/ml and forced vital capacity decreased from 2.47 L to 1.29 L. IgG, which was normal at the age of 28, increased and reached 5350 mg/dL.\\u003c/p\\u003e \\u003cp\\u003eRecent complete blood count showed white blood cells 4.5 x 10\\u003csup\\u003e3\\u003c/sup\\u003e /\\u0026micro;l (neutrophils 3.3 x 10\\u003csup\\u003e3\\u003c/sup\\u003e /\\u0026micro;l, lymphocytes 9.8 x 10\\u003csup\\u003e2\\u003c/sup\\u003e /\\u0026micro;l, monocytes 41/\\u0026micro;l, eosinophil 162/\\u0026micro;l, basophil 18/\\u0026micro;l ). Flow cytometry results showed a decrease in B cells and effector memory T cells, follicular helper T cells, natural killer cells and natural killer T cells while dendric cells were deficient. CD3 positive T cells and helper T cells were relatively increased (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Currently, she requires home oxygen therapy due to the progression of interstitial pneumonia (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ec) and pulmonary hypertension. Since she had schizophrenia, bone marrow transplant was not indicated, and a bone marrow biopsy has not been performed.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003ethe result of flow cytometry.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"3\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD19\\u0026thinsp;+\\u0026thinsp;CD20+\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.76%\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e**\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD20\\u0026thinsp;+\\u0026thinsp;CD21+\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.46%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD20\\u0026thinsp;+\\u0026thinsp;CD21-\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.32%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e*\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD19\\u0026thinsp;+\\u0026thinsp;CD27+\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.80%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD19\\u0026thinsp;+\\u0026thinsp;CD27-\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.26%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD3+\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e93.1%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD4+\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e50.1%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD45RO+\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e39.9%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCXCR5+ (follicular helper T)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6.89%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e**\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCCR6\\u0026thinsp;+\\u0026thinsp;CXCR3+ (Th1star)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e23.8%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e*\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD45RO-\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e15.0%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD45RA\\u0026thinsp;+\\u0026thinsp;CD31+(recent thymic emigrant)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e64.5%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD45RA\\u0026thinsp;+\\u0026thinsp;CD31-(上記以外)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e35.5%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e*\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD62L\\u0026thinsp;+\\u0026thinsp;CCR7+ (central memory)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e73.0%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD62L-CCR7- (effector memory)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e11.5%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e**\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTh1, Th2, Th17, Treg\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003enormal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD8+\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e45.0%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD45RO+\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e23.4%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD45RO-\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e25.7%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVa24\\u0026thinsp;+\\u0026thinsp;Vb11+ (NKT cell)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.002%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e**\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCD16\\u0026thinsp;+\\u0026thinsp;CD56+\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.20%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e**\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLineage- HLADR\\u0026thinsp;+\\u0026thinsp;CD123+ (plasmacytoid DC)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003ealmost 0%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e**\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLineage- HLADR\\u0026thinsp;+\\u0026thinsp;CD11c+ (classic DC)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003ealmost 0%\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e**\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"3\\\"\\u003e* indicates abnormal high value. ** indicate abnormal low value.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e\"},{\"header\":\"Discussion and Conclusions\",\"content\":\"\\u003cp\\u003eMany mutations have been detected in the \\u003cem\\u003eGATA2\\u003c/em\\u003e gene, and mutations related to diseases are most often in one of the two zinc finger-binding domains\\u003csup\\u003e4)\\u003c/sup\\u003e. In this case, the \\u003cem\\u003eGATA2\\u003c/em\\u003e mutation was found within the domain of zinc finger II.\\u003c/p\\u003e \\u003cp\\u003e \\u003cem\\u003eGATA\\u003c/em\\u003e2 gene mutations are known to cause haploinsufficiency\\u003csup\\u003e2)3)\\u003c/sup\\u003e, which lead to various phenotypic diseases. \\u003cem\\u003eGATA\\u003c/em\\u003e2 is a zinc finger transcription factor necessary for differentiation of endothelial and immature hematopoietic cells\\u003csup\\u003e6)\\u003c/sup\\u003e. \\u003cem\\u003eGATA\\u003c/em\\u003e2 is known to promote macrophage differentiation.\\u003csup\\u003e7)8)\\u003c/sup\\u003e Alveolar macrophage dysfunction in \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency and recurrent infection lead to damage of lung elastin, which also may contribute to the pulmonary changes seen in patients with \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency.\\u003csup\\u003e9)10)\\u003c/sup\\u003e The \\u003cem\\u003eGATA\\u003c/em\\u003e2 gene plays a functional role in the maintenance of helical ganglion cells and hearing ability, and its loss may result in hearing loss.\\u003csup\\u003e11)\\u003c/sup\\u003e In a cohort study of pediatric MDS patients with \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency, it was reported that 9% of patients presented with hearing loss.\\u003csup\\u003e12)\\u003c/sup\\u003e Association of psychiatric disease with \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency is unknown; 19% of pediatric MDS patients with \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency included behavioral problems such as autism and aggressive behavior, and neurological symptoms were seen in 8 of 484 patients with \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency \\u003csup\\u003e4)12)\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eIn the present case, the patient developed recurrent infection, sensorineural hearing loss, and erythema nodosum, all known manifestations of \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency\\u003csup\\u003e13)\\u003c/sup\\u003e, although no hematological malignancy developed. Based on the family history, it is likely that her mother had \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency, and she may have been genetically predisposed to schizophrenia from her father, not her mother. Therefore, the association between schizophrenia and \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency was unclear.\\u003c/p\\u003e \\u003cp\\u003eThe patient's history of repeated infections since childhood led us to suspect primary immunodeficiency, which led to the diagnosis of \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency. Flow cytometry of peripheral blood showed abnormalities in the composition of lymphocytes and that dendric cells were deficient. It has been reported that \\u003cem\\u003eGATA\\u003c/em\\u003e2 patients with MDS showed severe peripheral blood monocytopenia and B cell and NK cell lymphopenia, which is similar to what we have seen.\\u003csup\\u003e14)\\u003c/sup\\u003e Little has been reported on peripheral blood flow cytometry in \\u003cem\\u003eGATA\\u003c/em\\u003e2-deficient patients without hematological disease.\\u003c/p\\u003e \\u003cp\\u003ePulmonary diseases known to be associated with \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency include pulmonary alveolar proteinosis (PAP), pulmonary hypertension (PH), and non-tuberculous mycobacterial infection. PAP and PH have been reported to occur in 9% and 7% of patients with \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency, respectively\\u003csup\\u003e4)\\u003c/sup\\u003e. On the other hand, there is only one case report of \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency with interstitial pneumonia\\u003csup\\u003e5)\\u003c/sup\\u003e. In our present case, there was no evidence of PAP from bronchoscopy. She had no medications at her first visit to our clinic, and based on the clinical course and laboratory results, it is highly unlikely that she had drug-induced interstitial pneumonia or collagen-related interstitial pneumonia. As interstitial pneumonia progressed on chest CT, development of PAP could not be completely ruled out. Pulmonary hypertension was also observed, which considered an element of both \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency and/or the presence of lung disease (i.e., World Health Organization Group 3 and/or Group 5).\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, we present a patient with recurrent infections who in her 20s developed interstitial pneumonia and sensorineural hearing loss, leading to the diagnosis of \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency. Early-onset interstitial pneumonia may be a rare phenotype of \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cdiv class=\\\"DefinitionList\\\"\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003ePAP\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003epulmonary alveolar proteinosis\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003ePH\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003epulmonary hypertension\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNone of the authors have funding to declare.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData availability\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eData and materials are available from the corresponding author upon request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWritten informed consent for publication of the patient\\u0026rsquo;s clinical information and images were obtained by the patients.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor contribution:\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eYS collected clinical data and wrote the manuscript. TA, HU, AM, and GT contributed clinical data, reviewed, and edited the manuscript. KK and TM provided genetic information and conducted FACS analysis. HK came up with the study concept, contributed clinical data, and edited the manuscript. All authors approved the final version of the manuscript for publication.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e: The authors declare that they have no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements: Not applicable\\u003c/strong\\u003e\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eXabier Cortes-Lavaud et al. GATA2 germline mutations impair GATA2 transcription, causing haploinsufficiency: functional analysis of the p.Arg396Gln mutation \\u003cem\\u003eJ Immunol\\u003c/em\\u003e (2015) 194 (5): 2190\\u0026ndash;2198.\\u003c/li\\u003e\\n\\u003cli\\u003eMichael A et al. \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood, 2014; 123(6): 809\\u0026ndash;821\\u003c/li\\u003e\\n\\u003cli\\u003eAmy P et al. \\u003cem\\u003eGATA\\u003c/em\\u003e2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome. Blood, 2013; 121(19): 3830\\u0026ndash;3837\\u003c/li\\u003e\\n\\u003cli\\u003eBeatriz E Marciano et al. Pulmonary Manifestations of \\u003cem\\u003eGATA\\u003c/em\\u003e2 Deficiency. CHEST 2021;160(4):1350\\u0026ndash;1359\\u003c/li\\u003e\\n\\u003cli\\u003eTamara S et al. Diffuse parenchymal lung disease as first clinical manifestation of \\u003cem\\u003eGATA\\u003c/em\\u003e-2 deficiency in childhood. BMC Pulmonary Medicine 2015 Feb 10; 15:8\\u003c/li\\u003e\\n\\u003cli\\u003eCohen JI (2017) \\u003cem\\u003eGATA2\\u003c/em\\u003e Deficiency and Epstein\\u0026ndash;Barr Virus Disease. Front. Immunol. 8:1869. doi: 10.3389/fimmu.2017.01869\\u003c/li\\u003e\\n\\u003cli\\u003eKenji K et al. Redirecting differentiation of hematopoietic progenitors by a transcription factor, \\u003cem\\u003eGATA\\u003c/em\\u003e-2. Blood. 2006; 107: 1857\\u0026ndash;1863\\u003c/li\\u003e\\n\\u003cli\\u003eNeil P et al. \\u003cem\\u003eGATA\\u003c/em\\u003e-2 regulates granulocyte-macrophage progenitor cell function. Blood. 2008; 112: 4862\\u0026ndash;4873\\u003c/li\\u003e\\n\\u003cli\\u003eTang X et al. Down-regulation of \\u003cem\\u003eGATA\\u003c/em\\u003e-2 transcription during Pneumocystis carinii infection. Infect Immun. 2000; 68: 4720\\u0026ndash;4724\\u003c/li\\u003e\\n\\u003cli\\u003eMark E Lasbury et al. Effect of transcription factor \\u003cem\\u003eGATA\\u003c/em\\u003e-2 on phagocytic activity of alveolar macrophages from Pneumocystis carinii-infected hosts. Infect Immun. 2003; 71: 4943\\u0026ndash;4952\\u003c/li\\u003e\\n\\u003cli\\u003eTomofumi Hoshino et al. Spiral ganglion cell degeneration-induced deafness as a consequence of reduced \\u003cem\\u003eGATA\\u003c/em\\u003e factor activity. Genes to Cells 2019; 24(8):534\\u0026ndash;545\\u003c/li\\u003e\\n\\u003cli\\u003eMarcin W Wlodarski et al. Prevalence, clinical characteristic, and prognosis of \\u003cem\\u003eGATA\\u003c/em\\u003e2-related myelodysplastic syndromes in children and adolescents. CME 2016; 127(11):1387\\u0026ndash;1397\\u003c/li\\u003e\\n\\u003cli\\u003eClaire C et al. \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency syndrome; A decade of discovery. Human Mutation 2021; 42(11): 1365\\u0026ndash;1517\\u003c/li\\u003e\\n\\u003cli\\u003eKarthik A Ganapathi et al. \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency-associated bone marrow disorder differs from idiopathic asplastic anemia. Blood 2015; 125(1):56\\u0026ndash;70\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"GATA2 deficiency, interstitial pneumonia, hearing loss\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4090026/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4090026/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e \\u003cp\\u003e \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency is a rare disease caused by a germline heterozygous mutation in the \\u003cem\\u003eGATA\\u003c/em\\u003e2 gene. This mutation is known to cause a decrease in hematopoietic stem cells and a decrease in monocytes, dendritic cells, NK cells, and B cells, leading to various diseases such as hematological, infectious, and respiratory diseases.\\u003c/p\\u003e\\u003ch2\\u003eCase presentation:\\u003c/h2\\u003e \\u003cp\\u003eIn this study, we present a case in which a patient in her 20s developed sensorineural hearing loss, schizophrenia, and interstitial pneumonia, leading to the diagnosis of \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency. The patient later developed pulmonary hypertension as the interstitial pneumonia progressed.\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eEarly-onset interstitial pneumonia may be a rare phenotype of \\u003cem\\u003eGATA\\u003c/em\\u003e2 deficiency.\\u003c/p\\u003e\",\"manuscriptTitle\":\"GATA2 deficiency with early-onset interstitial pneumonia\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-04-09 12:33:30\",\"doi\":\"10.21203/rs.3.rs-4090026/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"2cba7a8c-923e-414f-bf37-99780b82a544\",\"owner\":[],\"postedDate\":\"April 9th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-04-23T13:02:35+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-04-09 12:33:30\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4090026\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4090026\",\"identity\":\"rs-4090026\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}