{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:45Z","timestamp":1790017965895,"version":"4.0.1"},"reference-count":113,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"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>Reversion mosaicism has been reported in an increasing number of genetic disorders including primary immunodeficiency diseases. Several mechanisms can mediate somatic reversion of inherited mutations. Back mutations restore wild-type sequences, whereas second-site mutations result in compensatory changes. In addition, intragenic recombination, chromosomal deletions, and copy-neutral loss of heterozygosity have been demonstrated in mosaic individuals. Revertant cells that have regained wild-type function may be associated with milder disease phenotypes in some immunodeficient patients with reversion mosaicism. Revertant cells can also be responsible for immune dysregulation. Studies identifying a large variety of genetic changes in the same individual further support a frequent occurrence of reversion mosaicism in primary immunodeficiency diseases. This phenomenon also provides unique opportunities to evaluate the biological effects of restored gene expression in different cell lineages. In this paper, we review the recent findings of reversion mosaicism in primary immunodeficiency diseases and discuss its clinical implications.<\/jats:p>","DOI":"10.3389\/fimmu.2021.783022","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T01:06:41Z","timestamp":1637024801000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Reversion Mosaicism in Primary Immunodeficiency Diseases"],"prefix":"10.3389","volume":"12","author":[{"given":"Hanae","family":"Miyazawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taizo","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.09.009","article-title":"Unexpected Relevant Role of Gene Mosaicism in Patients With Primary Immunodeficiency Diseases","volume":"143","author":"Mensa-Vilar\u00f3","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-021-01037-z","article-title":"Genetic Mosaicism as a Cause of Inborn Errors of Immunity","volume":"41","author":"Aluri","year":"2021","journal-title":"J Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0139-x","article-title":"Somatic Genetic Rescue in Mendelian Haematopoietic Diseases","volume":"20","author":"Revy","year":"2019","journal-title":"Nat Rev Genet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e328314b651","article-title":"Somatic Mosaicism in Primary Immune Deficiencies","volume":"8","author":"Wada","year":"2008","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.077511","article-title":"A Reversion of an IL2RG Mutation in Combined Immunodeficiency Providing Competitive Advantage to the Majority of CD8+ T Cells","volume":"98","author":"Kuijpers","year":"2013","journal-title":"Haematologica"},{"key":"B6","first-page":"59","article-title":"Somatic Mosaicism for a Newly Identified Splice-Site Mutation in a Patient With Adenosine Deaminase-Deficient Immunodeficiency and Spontaneous Clinical Recovery","volume":"55","author":"Hirschhorn","year":"1994","journal-title":"Am J Hum Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199611213352104","article-title":"Atypical X-Linked Severe Combined Immunodeficiency Due to Possible Spontaneous Reversion of the Genetic Defect in T Cells","volume":"335","author":"Stephan","year":"1996","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.1.274","article-title":"Diversity, Functionality, and Stability of the T Cell Repertoire Derived In Vivo From a Single Human T Cell Precursor","volume":"97","author":"Bousso","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-149708","article-title":"Detection of T Lymphocytes With a Second-Site Mutation in Skin Lesions of Atypical X-Linked Severe Combined Immunodeficiency Mimicking Omenn Syndrome","volume":"112","author":"Wada","year":"2008","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-153361","article-title":"Clinical and Immunologic Consequences of a Somatic Reversion in a Patient With X-Linked Severe Combined Immunodeficiency","volume":"112","author":"Speckmann","year":"2008","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9684-1","article-title":"Multiple Reversions of an IL2RG Mutation Restore T Cell Function in an X-Linked Severe Combined Immunodeficiency Patient","volume":"32","author":"Kawai","year":"2012","journal-title":"J Clin Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0174-0","article-title":"IL2RG Reversion Event in a Common Lymphoid Progenitor Leads to Delayed Diagnosis and Milder Phenotype","volume":"35","author":"Hsu","year":"2015","journal-title":"J Clin Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0202-0","article-title":"Late-Onset Combined Immunodeficiency With a Novel IL2RG Mutation and Probable Revertant Somatic Mosaicism","volume":"35","author":"Okuno","year":"2015","journal-title":"J Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-0936","article-title":"Oligoclonal Expansion of T Lymphocytes With Multiple Second-Site Mutations Leads to Omenn Syndrome in a Patient With RAG1-Deficient Severe Combined Immunodeficiency","volume":"106","author":"Wada","year":"2005","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0051-2","article-title":"RAG1 Reversion Mosaicism in a Patient With Omenn Syndrome","volume":"34","author":"Crestani","year":"2014","journal-title":"J Clin Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa053750","article-title":"Inherited and Somatic CD3\u03b6 Mutations in a Patient With T-Cell Deficiency","volume":"354","author":"Rieux-Laucat","year":"2006","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jaci.2016.06.020","article-title":"Primary T-Cell Immunodeficiency With Functional Revertant Somatic Mosaicism in CD247","volume":"139","author":"Marin","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-762864","article-title":"Analysis of the Recovery of CD247 Expression in a PID Patient: Insights Into the Spontaneous Repair of Defective Genes","volume":"130","author":"Bl\u00e1zquez-Moreno","year":"2017","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.jaci.2020.04.045","article-title":"Protein Functionality as a Potential Bottleneck for Somatic Revertant Variants","volume":"147","author":"Kaiser","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1182\/blood.V92.2.699","article-title":"A Case of Wiskott\u2013Aldrich Syndrome With Dual Mutations in Exon 10 of the WASP Gene: An Additional De Novo One-Base Insertion, Which Restores Frame Shift Due to an Inherent One-Base Deletion, Detected in the Major Population of the Patient\u2019s Peripheral Blood Lymphocytes","volume":"92","author":"Ariga","year":"1998","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.8.5245","article-title":"Spontaneous In Vivo Reversion of an Inherited Mutation in the Wiskott\u2013Aldrich Syndrome","volume":"166","author":"Ariga","year":"2001","journal-title":"J Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-007-9121-z","article-title":"The Phenomenon of Spontaneous Genetic Reversions in the Wiskott\u2013Aldrich Syndrome: A Report of the Workshop of the ESID Genetics Working Party at the XIIth Meeting of the European Society for Immunodeficiencies (ESID). Budapest, Hungary October 4-7, 2006","volume":"27","author":"Stewart","year":"2007","journal-title":"J Clin Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/j.1399-0004.2008.01019.x","article-title":"Multiple Independent Second-Site Mutations in Two Siblings With Somatic Mosaicism for Wiskott\u2013Aldrich Syndrome","volume":"74","author":"Boztug","year":"2008","journal-title":"Clin Genet"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-095299","article-title":"Unprecedented Diversity of Genotypic Revertants in Lymphocytes of a Patient With Wiskott\u2013Aldrich Syndrome","volume":"111","author":"Davis","year":"2008","journal-title":"Blood"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e3444","DOI":"10.1371\/journal.pone.0003444","article-title":"Evolution of Highly Polymorphic T Cell Populations in Siblings With the Wiskott\u2013Aldrich Syndrome","volume":"3","author":"Lutskiy","year":"2008","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.clim.2009.12.011","article-title":"Somatic Mosaicism in the Wiskott\u2013Aldrich Syndrome: Molecular and Functional Characterization of Genotypic Revertants","volume":"135","author":"Davis","year":"2010","journal-title":"Clin Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.jaci.2009.11.034","article-title":"Revertant T Lymphocytes in a Patient With Wiskott\u2013Aldrich Syndrome: Analysis of Function and Distribution in Lymphoid Organs","volume":"125","author":"Trifari","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2015.04.001","article-title":"In Vivo Reversion of an Inherited Mutation in a Chinese Patient With Wiskott\u2013Aldrich Syndrome","volume":"76","author":"Xie","year":"2015","journal-title":"Hum Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151260498","article-title":"Somatic Mosaicism in Wiskott\u2013Aldrich Syndrome Suggests In Vivo Reversion by a DNA Slippage Mechanism","volume":"98","author":"Wada","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15485","article-title":"Second-Site Mutation in the Wiskott\u2013Aldrich Syndrome (WAS) Protein Gene Causes Somatic Mosaicism in Two WAS Siblings","volume":"111","author":"Wada","year":"2003","journal-title":"J Clin Invest"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0846","article-title":"Multiple Patients With Revertant Mosaicism in a Single Wiskott\u2013Aldrich Syndrome Family","volume":"104","author":"Wada","year":"2004","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1739","article-title":"Differential Contribution of Wiskott\u2013Aldrich Syndrome Protein to Selective Advantage in T- and B-Cell Lineages","volume":"103","author":"Konno","year":"2004","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4724","article-title":"Mosaicism of NK Cells in a Patient With Wiskott\u2013Aldrich Syndrome","volume":"106","author":"Lutskiy","year":"2005","journal-title":"Blood"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20308","article-title":"A Second-Site Mutation in the Initiation Codon of WAS (WASP) Results in Expansion of Subsets of Lymphocytes in an Wiskott\u2013Aldrich Syndrome Patient","volume":"27","author":"Du","year":"2006","journal-title":"Hum Mutat"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29539","article-title":"Wiskott\u2013Aldrich Syndrome Protein Is Required for Regulatory T Cell Homeostasis","volume":"117","author":"Humblet-Baron","year":"2007","journal-title":"J Clin Invest"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11222","article-title":"Large Granular Lymphocyte Proliferation and Revertant Mosaicism: Two Rare Events in a Wiskott\u2013Aldrich Syndrome Patient","volume":"92","author":"Boztug","year":"2007","journal-title":"Haematologica"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e20190607","DOI":"10.1084\/jem.20190607","article-title":"Gene Therapy for Severe Combined Immunodeficiencies and Beyond","volume":"217","author":"Fischer","year":"2020","journal-title":"J Exp Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233151","article-title":"Lentivirus-Based Gene Therapy of Hematopoietic Stem Cells in Wiskott\u2013Aldrich Syndrome","volume":"341","author":"Aiuti","year":"2013","journal-title":"Science"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-008-8091-4","article-title":"Revertant Somatic Mosaicism in the Wiskott\u2013Aldrich Syndrome","volume":"44","author":"Davis","year":"2009","journal-title":"Immunol Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s10875-017-0453-z","article-title":"Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott\u2013Aldrich Syndrome","volume":"38","author":"Candotti","year":"2018","journal-title":"J Clin Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.581119","article-title":"Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse","volume":"11","author":"Mastio","year":"2020","journal-title":"Front Immunol"},{"key":"B42","volume-title":"Stiehm\u2019s Immune Deficiencies: Inborn Errors of Immunity","author":"Sullivan","year":"2020"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-159249","article-title":"Mutations of the Wiskott\u2013Aldrich Syndrome Protein (WASP): Hotspots, Effect on Transcription, and Translation and Phenotype\/Genotype Correlation","volume":"104","author":"Jin","year":"2004","journal-title":"Blood"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30465","article-title":"Revertant Mosaicism in Junctional Epidermolysis Bullosa Due to Multiple Correcting Second-Site Mutations in LAMB3","volume":"117","author":"Pasmooij","year":"2007","journal-title":"J Clin Invest"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81050-8","article-title":"Wiskott\u2013Aldrich Syndrome Protein, a Novel Effector for the GTPase CDC42Hs, Is Implicated in Actin Polymerization","volume":"84","author":"Symons","year":"1996","journal-title":"Cell"},{"key":"B46","doi-asserted-by":"publisher","first-page":"37ps31","DOI":"10.1126\/scitranslmed.3001336","article-title":"Alternative Control: What\u2019s WASp Doing in the Nucleus","volume":"2","author":"Teitell","year":"2010","journal-title":"Sci Transl Med"},{"key":"B47","doi-asserted-by":"publisher","first-page":"37ra44","DOI":"10.1126\/scitranslmed.3000813","article-title":"Nuclear Role of WASp in the Pathogenesis of Dysregulated TH1 Immunity in Human Wiskott\u2013Aldrich Syndrome","volume":"2","author":"Taylor","year":"2010","journal-title":"Sci Transl Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-07-587642","article-title":"Disruption of hSWI\/SNF Complexes in T Cells by WAS Mutations Distinguishes X-Linked Thrombocytopenia From Wiskott\u2013Aldrich Syndrome","volume":"124","author":"Sarkar","year":"2014","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302923","article-title":"Nuclear Role of WASp in Gene Transcription Is Uncoupled From Its ARP2\/3-Dependent Cytoplasmic Role in Actin Polymerization","volume":"193","author":"Sadhukhan","year":"2014","journal-title":"J Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-05-646182","article-title":"SUMOylation-Disrupting WAS Mutation Converts WASp From a Transcriptional Activator to a Repressor of NF-kB Response Genes in T Cells","volume":"126","author":"Sarkar","year":"2015","journal-title":"Blood"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.11.023","article-title":"R-Loops Cause Genomic Instability in Wiskott\u2013Aldrich Syndrome T Helper Lymphocytes","volume":"142","author":"Sarkar","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0237-5","article-title":"Nuclear Arp2\/3 Drives DNA Break Clustering for Homology-Directed Repair","volume":"559","author":"Schrank","year":"2018","journal-title":"Nature"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.09.026","article-title":"Wiskott\u2013Aldrich Syndrome Protein Senses Irradiation-Induced DNA Damage to Coordinate the Cell-Protective Golgi Dispersal Response in Human T and B Lymphocytes","volume":"145","author":"Wen","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/ng0796-290","article-title":"Spontaneous In Vivo Reversion to Normal of an Inherited Mutation in a Patient With Adenosine Deaminase Deficiency","volume":"13","author":"Hirschhorn","year":"1996","journal-title":"Nat Genet"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v97.9.2896","article-title":"T-Cell Lines From 2 Patients With Adenosine Deaminase (ADA) Deficiency Showed the Restoration of ADA Activity Resulted From the Reversion of an Inherited Mutation","volume":"97","author":"Ariga","year":"2001","journal-title":"Blood"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v99.3.1005","article-title":"Adenosine Deaminase Deficiency With Mosaicism for a \u201cSecond-Site Suppressor\u201d of a Splicing Mutation: Decline in Revertant T Lymphocytes During Enzyme Replacement Therapy","volume":"99","author":"Arredondo-Vega","year":"2002","journal-title":"Blood"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.08.026","article-title":"Immunologic Reconstitution During PEG-ADA Therapy in an Unusual Mosaic ADA-Deficient Patient","volume":"130","author":"Liu","year":"2009","journal-title":"Clin Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2011.02593.x","article-title":"Somatic Mosaicism Caused by Monoallelic Reversion of a Mutation in T Cells of a Patient With ADA-SCID and the Effects of Enzyme Replacement Therapy on the Revertant Phenotype","volume":"74","author":"Moncada-V\u00e9lez","year":"2011","journal-title":"Scand J Immunol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"273ra13","DOI":"10.1126\/scitranslmed.3010314","article-title":"In Vivo Tracking of T Cells in Humans Unveils Decade-Long Survival and Activity of Genetically Modified T Memory Stem Cells","volume":"7","author":"Biasco","year":"2015","journal-title":"Sci Transl Med"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000231907.50290.6f","article-title":"Omenn Syndrome: A Lack of Tolerance on the Background of Deficient Lymphocyte Development and Maturation","volume":"18","author":"H\u00f6nig","year":"2006","journal-title":"Curr Opin Rheumatol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.55.115","article-title":"Omenn Syndrome\u2013Review of Several Phenotypes of Omenn Syndrome and RAG1\/RAG2 Mutations in Japan","volume":"55","author":"Kato","year":"2006","journal-title":"Allergol Int"},{"key":"B62","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.154.10.5103","article-title":"Cell Expansion and Growth Arrest Phases During the Transition From Precursor (CD4-8-) to Immature (CD4+8+) Thymocytes in Normal and Genetically Modified Mice","volume":"154","author":"P\u00e9nit","year":"1995","journal-title":"J Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-043166","article-title":"T-B+NK+ Severe Combined Immunodeficiency Caused by Complete Deficiency of the CD3\u03b6 Subunit of the T-Cell Antigen Receptor Complex","volume":"109","author":"Roberts","year":"2007","journal-title":"Blood"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0088-2","article-title":"Combined Immunodeficiency Evolving Into Predominant CD4+ Lymphopenia Caused by Somatic Chimerism in JAK3","volume":"34","author":"Ban","year":"2014","journal-title":"J Clin Immunol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.clim.2015.12.016","article-title":"Molecular and Immunological Characterization of DNA Ligase IV Deficiency","volume":"163","author":"Jiang","year":"2016","journal-title":"Clin Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12421","article-title":"Vaccine-Associated Varicella and Rubella Infections in Severe Combined Immunodeficiency With Isolated CD4 Lymphocytopenia and Mutations in IL7R Detected by Tandem Whole Exome Sequencing and Chromosomal Microarray","volume":"178","author":"Bayer","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/s1471-4914(01)02154-2","article-title":"NEMO\/Ikk\u03b3: Linking NF-\u03bab to Human Disease","volume":"7","author":"Courtois","year":"2001","journal-title":"Trends Mol Med"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.12-RAI-0446","article-title":"Diagnosis and Treatment in Anhidrotic Ectodermal Dysplasia With Immunodeficiency","volume":"61","author":"Kawai","year":"2012","journal-title":"Allergol Int"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-354167","article-title":"Frequent Somatic Mosaicism of NEMO in T Cells of Patients With X-Linked Anhidrotic Ectodermal Dysplasia With Immunodeficiency","volume":"119","author":"Kawai","year":"2012","journal-title":"Blood"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3655","article-title":"X-Linked Ectodermal Dysplasia and Immunodeficiency Caused by Reversion Mosaicism of NEMO Reveals a Critical Role for NEMO in Human T-Cell Development and\/or Survival","volume":"103","author":"Nishikomori","year":"2004","journal-title":"Blood"},{"key":"B71","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s10875-011-9600-0","article-title":"Successful Treatment With Infliximab for Inflammatory Colitis in a Patient With X-Linked Anhidrotic Ectodermal Dysplasia With Immunodeficiency","volume":"32","author":"Mizukami","year":"2012","journal-title":"J Clin Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/nature05698","article-title":"Epithelial NEMO Links Innate Immunity to Chronic Intestinal Inflammation","volume":"446","author":"Nenci","year":"2007","journal-title":"Nature"},{"key":"B73","volume-title":"Stiehm\u2019s Immune Deficiencies: Inborn Errors of Immunity","author":"Sullivan","year":"2020"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-039057","article-title":"Somatic Revertant Mosaicism in a Patient With Leukocyte Adhesion Deficiency Type 1","volume":"109","author":"Tone","year":"2007","journal-title":"Blood"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-082552","article-title":"Reversion Mutations in Patients With Leukocyte Adhesion Deficiency Type-1 (LAD-1)","volume":"111","author":"Uzel","year":"2008","journal-title":"Blood"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0086-4","article-title":"Successful Anti-TNF-\u03b1 Treatment in a Girl With LAD-1 Disease and Autoimmune Manifestations","volume":"34","author":"Marsili","year":"2014","journal-title":"J Clin Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612197","article-title":"Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1","volume":"376","author":"Moutsopoulos","year":"2017","journal-title":"N Engl J Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112391","article-title":"Expansion of Somatically Reverted Memory CD8+ T Cells in Patients With X-Linked Lymphoproliferative Disease Caused by Selective Pressure From Epstein\u2013Barr Virus","volume":"209","author":"Palendira","year":"2012","journal-title":"J Exp Med"},{"key":"B79","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.jaci.2018.07.044","article-title":"Modification of Cellular and Humoral Immunity by Somatically Reverted T Cells in X-Linked Lymphoproliferative Syndrome Type 1","volume":"143","author":"Hoshino","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.clim.2017.06.003","article-title":"DOCK8 Deficiency: Insights Into Pathophysiology, Clinical Features and Management","volume":"181","author":"Biggs","year":"2017","journal-title":"Clin Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.03.02","article-title":"Somatic Reversion in Dedicator of Cytokinesis 8 Immunodeficiency Modulates Disease Phenotype","volume":"133","author":"Jing","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e142434","DOI":"10.1172\/JCI142434","article-title":"Somatic Reversion of Pathogenic DOCK8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure DOCK8 Deficiency","volume":"131","author":"Pillay","year":"2021","journal-title":"J Clin Invest"},{"key":"B83","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.clim.2015.12.003","article-title":"Hypomorphic Function and Somatic Reversion of DOCK8 Cause Combined Immunodeficiency Without Hyper-IgE","volume":"163","author":"Kienzler","year":"2016","journal-title":"Clin Immunol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"16719","DOI":"10.1038\/s41598-018-34953-z","article-title":"Somatic Alterations Compromised Molecular Diagnosis of DOCK8 Hyper-IgE Syndrome Caused by a Novel Intronic Splice Site Mutation","volume":"8","author":"Hagl","year":"2018","journal-title":"Sci Rep"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.673487","article-title":"Case Report: Hypomorphic Function and Somatic Reversion in DOCK8 Deficiency in One Patient With Two Novel Variants and Sclerosing Cholangitis","volume":"12","author":"Saettini","year":"2021","journal-title":"Front Immunol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-631374","article-title":"Omenn Syndrome Associated With a Functional Reversion Due to a Somatic Second-Site Mutation in CARD11 Deficiency","volume":"126","author":"Fuchs","year":"2015","journal-title":"Blood"},{"key":"B87","doi-asserted-by":"publisher","first-page":"e51","DOI":"10.1371\/journal.pbio.1000051","article-title":"Commitment to the Regulatory T Cell Lineage Requires CARMA1 in the Thymus But Not in the Periphery","volume":"7","author":"Barnes","year":"2009","journal-title":"PLoS Biol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900498","article-title":"CARMA1 Controls an Early Checkpoint in the Thymic Development of FoxP3 Regulatory T Cells","volume":"182","author":"Molinero","year":"2009","journal-title":"J Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-07-863431","article-title":"T-Cell Defects in Patients With ARPC1B Germline Mutations Account for Combined Immunodeficiency","volume":"132","author":"Brigida","year":"2018","journal-title":"Blood"},{"key":"B90","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.jaci.2016.09.061","article-title":"Combined Immunodeficiency With Severe Inflammation and Allergy Caused by ARPC1B Deficiency","volume":"140","author":"Kuijpers","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14816","article-title":"Loss of the Arp2\/3 Complex Component ARPC1B Causes Platelet Abnormalities and Predisposes to Inflammatory Disease","volume":"8","author":"Kahr","year":"2017","journal-title":"Nat Commun"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.02.003","article-title":"A Combined Immunodeficiency With Severe Infections, Inflammation, and Allergy Caused by ARPC1B Deficiency","volume":"143","author":"Volpi","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1172\/JCI129388","article-title":"Loss of ARPC1B Impairs Cytotoxic T Lymphocyte Maintenance and Cytolytic Activity","volume":"129","author":"Randzavola","year":"2019","journal-title":"J Clin Invest"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1016\/j.jaci.2015.06.008","article-title":"An In Vivo Genetic Reversion Highlights the Crucial Role of Myb-Like, SWIRM, and MPN Domains 1 (MYSM1) in Human Hematopoiesis and Lymphocyte Differentiation","volume":"136","author":"Le Guen","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-019-00665-w","article-title":"WHIM Syndrome: From Pathogenesis Towards Personalized Medicine and Cure","volume":"39","author":"Heusinkveld","year":"2019","journal-title":"J Clin Immunol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"e1073430","DOI":"10.1080\/21675511.2015.1073430","article-title":"Chromothriptic Cure of WHIM Syndrome: Implications for Bone Marrow Transplantation","volume":"3","author":"Mcdermott","year":"2015","journal-title":"Rare Dis"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2017.08.005","article-title":"Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis","volume":"27","author":"Ly","year":"2017","journal-title":"Trends Cell Biol"},{"key":"B98","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":"B99","volume-title":"Stiehm\u2019s Immune Deficiencies: Inborn Errors of Immunity","author":"Sullivan","year":"2020"},{"key":"B100","volume-title":"Stiehm\u2019s Immune Deficiencies: Inborn Errors of Immunity","author":"Sullivan","year":"2020"},{"key":"B101","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":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3569","article-title":"SAMD9 Mutations Cause a Novel Multisystem Disorder, MIRAGE Syndrome, and Are Associated With Loss of Chromosome 7","volume":"48","author":"Narumi","year":"2016","journal-title":"Nat Genet"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-105020","article-title":"Two Patients With MIRAGE Syndrome Lacking Haematological Features: Role of Somatic Second-Site Reversion SAMD9 Mutations","volume":"55","author":"Shima","year":"2018","journal-title":"J Med Genet"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.04.009","article-title":"Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L","volume":"98","author":"Chen","year":"2016","journal-title":"Am J Hum Genet"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-743302","article-title":"Gain-Of-Function SAMD9L Mutations Cause a Syndrome of Cytopenia, Immunodeficiency, MDS, and Neurological Symptoms","volume":"129","author":"Tesi","year":"2017","journal-title":"Blood"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.142","article-title":"Germline SAMD9 Mutation in Siblings With Monosomy 7 and Myelodysplastic Syndrome","volume":"31","author":"Schwartz","year":"2017","journal-title":"Leukemia"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91913","article-title":"Somatic Mutations and Progressive Monosomy Modify SAMD9-Related Phenotypes in Humans","volume":"127","author":"Buonocore","year":"2017","journal-title":"J Clin Invest"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.180778","article-title":"Constitutional SAMD9L Mutations Cause Familial Myelodysplastic Syndrome and Transient Monosomy 7","volume":"103","author":"Pastor","year":"2018","journal-title":"Haematologica"},{"key":"B109","doi-asserted-by":"publisher","first-page":"e121086","DOI":"10.1172\/jci.insight.121086","article-title":"Germline SAMD9 and SAMD9L Mutations Are Associated With Extensive Genetic Evolution and Diverse Hematologic Outcomes","volume":"3","author":"Wong","year":"2018","journal-title":"JCI Insight"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00625","article-title":"Reversion SAMD9 Mutations Modifying Phenotypic Expression of MIRAGE Syndrome and Allowing Inheritance in a Usually De Novo Disorder","volume":"10","author":"Roucher-Boulez","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B111","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nm.4241","article-title":"T Memory Stem Cells in Health and Disease","volume":"23","author":"Gattinoni","year":"2017","journal-title":"Nat Med"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05916.x","article-title":"Myeloid Lineage-Selective Growth of Revertant Cells in Fanconi Anaemia","volume":"132","author":"Hamanoue","year":"2006","journal-title":"Br J Haematol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2019.09.005","article-title":"Somatic Variants: New Kids on the Block in Human Immunogenetics","volume":"35","author":"Van Horebeek","year":"2019","journal-title":"Trends Genet"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.783022\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T02:24:17Z","timestamp":1673749457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.783022\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,16]]},"references-count":113,"alternative-id":["10.3389\/fimmu.2021.783022"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.783022","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,16]]},"article-number":"783022"}}