{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:08:38Z","timestamp":1785892118676,"version":"3.56.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Education Research and Development Program of Chongqing","award":["2019-9-66"],"award-info":[{"award-number":["2019-9-66"]}]},{"name":"Talent Program of Hunan Children\u2019s Hospital","award":["1233"],"award-info":[{"award-number":["1233"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1007\/s10875-022-01373-8","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T11:02:40Z","timestamp":1664794960000},"page":"229-240","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Novel RAC2 Mutation Causing Combined Immunodeficiency"],"prefix":"10.1007","volume":"43","author":[{"given":"Liang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2054-8711","authenticated-orcid":false,"given":"Xiaodong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"issue":"3","key":"1373_CR1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.tcb.2005.01.002","volume":"15","author":"GM Bokoch","year":"2005","unstructured":"Bokoch GM. Regulation of innate immunity by Rho GTPases. Trends Cell Biol. 2005;15(3):163\u201371.","journal-title":"Trends Cell Biol"},{"key":"1373_CR2","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/S0076-6879(07)00427-2","volume":"439","author":"DA Williams","year":"2008","unstructured":"Williams DA, Zheng Y, Cancelas JA. Rho GTPases and regulation of hematopoietic stem cell localization. Methods Enzymol. 2008;439:365\u201393.","journal-title":"Methods Enzymol"},{"issue":"3","key":"1373_CR3","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.autrev.2008.07.044","volume":"8","author":"AB Pernis","year":"2009","unstructured":"Pernis AB. Rho GTPase-mediated pathways in mature CD4+ T cells. Autoimmun Rev. 2009;8(3):199\u2013203.","journal-title":"Autoimmun Rev"},{"issue":"9","key":"1373_CR4","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1038\/nrm2476","volume":"9","author":"SJ Heasman","year":"2008","unstructured":"Heasman SJ, Ridley AJ. Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol. 2008;9(9):690\u2013701.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"5","key":"1373_CR5","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1182\/blood-2009-09-198127","volume":"115","author":"JC Mulloy","year":"2010","unstructured":"Mulloy JC, Cancelas JA, Filippi MD, et al. Rho GTPases in hematopoiesis and hemopathies. Blood. 2010;115(5):936\u201347.","journal-title":"Blood"},{"issue":"8","key":"1373_CR6","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41577-021-00500-7","volume":"21","author":"R El Masri","year":"2021","unstructured":"El Masri R, Delon J. RHO GTPases: from new partners to complex immune syndromes. Nat Rev Immunol. 2021;21(8):499\u2013513.","journal-title":"Nat Rev Immunol"},{"issue":"15","key":"1373_CR7","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1016\/j.yexcr.2013.07.002","volume":"319","author":"A Troeger","year":"2013","unstructured":"Troeger A, Williams DA. Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders. Exp Cell Res. 2013;319(15):2375\u201383.","journal-title":"Exp Cell Res"},{"issue":"2","key":"1373_CR8","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1002\/JLB.5MR0520-194RR","volume":"108","author":"V Lougaris","year":"2020","unstructured":"Lougaris V, Baronio M, Gazzurelli L, et al. RAC2 and primary human immune deficiencies. J Leukoc Biol. 2020;108(2):687\u201396.","journal-title":"J Leukoc Biol"},{"issue":"9","key":"1373_CR9","doi-asserted-by":"publisher","first-page":"4654","DOI":"10.1073\/pnas.080074897","volume":"97","author":"DR Ambruso","year":"2000","unstructured":"Ambruso DR, Knall C, Abell AN, et al. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Natl Acad Sci U S A. 2000;97(9):4654\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"1373_CR10","first-page":"1646","volume":"96","author":"DA Williams","year":"2000","unstructured":"Williams DA, Tao W, Yang F, et al. Dominant negative mutation of the hematopoietic specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood. 2000;96(5):1646\u201354.","journal-title":"Blood"},{"key":"1373_CR11","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jaci.2010.10.013","volume":"127","author":"D Accetta","year":"2011","unstructured":"Accetta D, Syverson G, Bonacci B, et al. Human phagocyte defect caused by a Rac2 mutation detected by means of neonatal screening for T-cell lymphopenia. J Allergy Clin Immunol. 2011;127:535\u20138.","journal-title":"J Allergy Clin Immunol"},{"issue":"5","key":"1373_CR12","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.jaci.2014.10.039","volume":"135","author":"OK Alkhairy","year":"2015","unstructured":"Alkhairy OK, Rezaei N, Graham RR, et al. RAC2 loss-of-function mutation in 2 siblings with characteristics of common variable immunodeficiency. J Allergy Clin Immunol. 2015;135(5):1380-4.e1-5.","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"1373_CR13","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1016\/j.jaci.2019.01.001","volume":"143","author":"V Lougaris","year":"2019","unstructured":"Lougaris V, Chou J, Beano A, et al. A monoallelic activating mutation in RAC2 resulting in a combined immunodeficiency. J Allergy Clin Immunol. 2019;143(4):1649-1653.e3.","journal-title":"J Allergy Clin Immunol"},{"issue":"18","key":"1373_CR14","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1182\/blood-2018-11-886028","volume":"133","author":"AP Hsu","year":"2019","unstructured":"Hsu AP, Donk\u00f3 A, Arrington ME, et al. Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects. Blood. 2019;133(18):1977\u201388.","journal-title":"Blood"},{"key":"1373_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.clim.2019.05.003","volume":"205","author":"SO Sharapova","year":"2019","unstructured":"Sharapova SO, Haapaniemi E, Sakovich IS, et al. Heterozygous activating mutation in RAC2 causes infantile-onset combined immunodeficiency with susceptibility to viral infections. Clin Immunol. 2019;205:1\u20135.","journal-title":"Clin Immunol"},{"key":"1373_CR16","doi-asserted-by":"publisher","first-page":"108248","DOI":"10.1016\/j.clim.2019.108248","volume":"212","author":"BM Smits","year":"2020","unstructured":"Smits BM, Lelieveld PHC, Ververs FA, et al. A dominant activating RAC2 variant associated with immunodeficiency and pulmonary disease. Clin Immunol. 2020;212:108248.","journal-title":"Clin Immunol"},{"issue":"2","key":"1373_CR17","doi-asserted-by":"publisher","first-page":"404","DOI":"10.3324\/haematol.2019.230250","volume":"106","author":"C Lagresle-Peyrou","year":"2021","unstructured":"Lagresle-Peyrou C, Olichon A, Sadek H, et al. A gain-of- function RAC2 mutation is associated with bone-marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency. Haematologica. 2021;106(2):404\u201311.","journal-title":"Haematologica"},{"issue":"2","key":"1373_CR18","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s10875-020-00915-2","volume":"41","author":"H Stern","year":"2021","unstructured":"Stern H, Donk\u00f3 A, Shapiro T, et al. A novel RAC2 variant presenting as severe combined immunodeficiency. J Clin Immunol. 2021;41(2):473\u20136.","journal-title":"J Clin Immunol"},{"issue":"3","key":"1373_CR19","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1016\/j.jaci.2018.04.022","volume":"142","author":"Y Ding","year":"2018","unstructured":"Ding Y, Zhou L, Xia Y, et al. Reference values for peripheral blood lymphocyte subsets of healthy children in China. J Allergy Clin Immunol. 2018;142(3):970-973.e8.","journal-title":"J Allergy Clin Immunol"},{"key":"1373_CR20","first-page":"52184","volume":"94","author":"A Sottini","year":"2014","unstructured":"Sottini A, Serana F, Bertoli D, et al. Simultaneous quantification of T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs) by real-time PCR. J Vis Exp. 2014;94:52184.","journal-title":"J Vis Exp"},{"key":"1373_CR21","doi-asserted-by":"publisher","unstructured":"Zhang L, Chen Z, Li W, et al. Combined immunodeficiency caused by a novel de novo gain-of-function RAC2 mutation. J Clin Immunol. 2022 May 21. https:\/\/doi.org\/10.1007\/s10875-022-01288-4. Online ahead of print.","DOI":"10.1007\/s10875-022-01288-4"},{"issue":"4","key":"1373_CR22","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/ni.2234","volume":"13","author":"F Honda","year":"2012","unstructured":"Honda F, Kano H, Kanegane H, et al. The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils. Nat Immunol. 2012;13(4):369\u201378.","journal-title":"Nat Immunol"},{"issue":"2","key":"1373_CR23","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.molcel.2009.02.023","volume":"34","author":"TD Bunney","year":"2009","unstructured":"Bunney TD, Opaleye O, Roe SM, et al. Structural insights into formation of an active signaling complex between Rac and phospholipase C Gamma 2. Mol Cell. 2009;34(2):223\u201333.","journal-title":"Mol Cell"},{"issue":"5","key":"1373_CR24","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, et al. ACMG Laboratory Quality Assurance Committee Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"key":"1373_CR25","doi-asserted-by":"publisher","first-page":"108257","DOI":"10.1016\/j.clim.2019.108257","volume":"208","author":"G Tabellini","year":"2019","unstructured":"Tabellini G, Baronio M, Patrizi O, et al. The RAC2-PI3K axis regulates human NK cell maturation and function. Clin Immunol. 2019;208:108257.","journal-title":"Clin Immunol"},{"issue":"1","key":"1373_CR26","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/imr.12791","volume":"291","author":"S Latour","year":"2019","unstructured":"Latour S, Fischer A. Signaling pathways involved in the T-cell-mediated immunity against Epstein-Barr virus: Lessons from genetic diseases. Immunol Rev. 2019;291(1):174\u201389.","journal-title":"Immunol Rev"},{"key":"1373_CR27","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3389\/fimmu.2018.00237","volume":"9","author":"JI Cohen","year":"2018","unstructured":"Cohen JI. Herpesviruses in the activated phosphatidylinositol-3-kinase-\u03b4 syndrome. Front Immunol. 2018;9:237.","journal-title":"Front Immunol"},{"issue":"11","key":"1373_CR28","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/nri.2016.93","volume":"16","author":"CL Lucas","year":"2016","unstructured":"Lucas CL, Chandra A, Nejentsev S, et al. PI3K\u03b4 and primary immunodeficiencies. Nat Rev Immunol. 2016;16(11):702\u201314.","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"1373_CR29","doi-asserted-by":"publisher","first-page":"71","DOI":"10.4161\/21541248.2014.989789","volume":"6","author":"CC Campa","year":"2015","unstructured":"Campa CC, Ciraolo E, Ghigo A, et al. Crossroads of PI3K and Rac pathways. Small GTPases. 2015;6(2):71\u201380.","journal-title":"Small GTPases"},{"issue":"4","key":"1373_CR30","first-page":"884","volume":"27","author":"JK Weeks","year":"2006","unstructured":"Weeks JK, Helton KJ, Conley ME, et al. Diffuse CNS vasculopathy with chronic Epstein-Barr virus infection in X-linked lymphoproliferative disease. AJNR Am J Neuroradiol. 2006;27(4):884\u20136.","journal-title":"AJNR Am J Neuroradiol"},{"issue":"11","key":"1373_CR31","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1007\/s00415-007-0619-3","volume":"254","author":"JH Kim","year":"2007","unstructured":"Kim JH, Joo BE, Koh SB. Serial diffusion-weighted MR imaging findings in a patient with Epstein-Barr virus encephalitis. J Neurol. 2007;254(11):1616\u20138.","journal-title":"J Neurol"},{"issue":"2","key":"1373_CR32","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.jaci.2016.06.021","volume":"139","author":"TI Coulter","year":"2017","unstructured":"Coulter TI, Chandra A, Bacon CM, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase \u03b4 syndrome: a large patient cohort study. J Allergy Clin Immunol. 2017;139(2):597-606.e4.","journal-title":"J Allergy Clin Immunol"},{"issue":"9","key":"1373_CR33","doi-asserted-by":"publisher","first-page":"3239","DOI":"10.1172\/JCI62949","volume":"122","author":"A Crequer","year":"2012","unstructured":"Crequer A, Troeger A, Patin E, et al. Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections. J Clin Invest. 2012;122(9):3239\u201347.","journal-title":"J Clin Invest"},{"issue":"4","key":"1373_CR34","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1128\/MCB.22.4.1158-1171.2002","volume":"22","author":"X Li","year":"2002","unstructured":"Li X, Bu X, Lu B, et al. The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function. Mol Cell Biol. 2002;22(4):1158\u201371.","journal-title":"Mol Cell Biol"},{"issue":"6\u20137","key":"1373_CR35","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1007\/s00439-020-02131-9","volume":"139","author":"C Gruber","year":"2020","unstructured":"Gruber C, Bogunovic D. Incomplete penetrance in primary immunodefciency: a skeleton in the closet. Hum Genet. 2020;139(6\u20137):745\u201357.","journal-title":"Hum Genet"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-022-01373-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-022-01373-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-022-01373-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T07:13:13Z","timestamp":1673680393000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-022-01373-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,3]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["1373"],"URL":"https:\/\/doi.org\/10.1007\/s10875-022-01373-8","relation":{},"ISSN":["0271-9142","1573-2592"],"issn-type":[{"value":"0271-9142","type":"print"},{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,3]]},"assertion":[{"value":"1 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Medical Ethics Committee of Hunan Children\u2019s Hospital (Approval number: HCHLL-2022\u201310).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from the patient and her parents, in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Written informed consent was obtained from all participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Publish"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}