{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:56:08Z","timestamp":1781636168050,"version":"3.54.5"},"reference-count":136,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche Scientifique-TUBITAK","award":["GENEX-ARCA 2024_2027"],"award-info":[{"award-number":["GENEX-ARCA 2024_2027"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ataxia telangiectasia (AT) is an autosomal recessive neurodegenerative disease. While heterozygous relatives of AT patients are known to be clinically healthy, a predisposition to various pathologies has been reported. Our aim was firstly, to further characterize the clinical features and broaden the spectrum of genetic pathogenic variants in AT patients. Secondly, we aimed to study the immune profiles of AT patients and their relatives to identify similarities or common biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A Target Gene Sequencing for six patients suspected with AT was performed. Computational analysis was conducted to assess the pathogenicity of novel variants. The distribution of immune cells was assessed by flow cytometry in patients with AT, AT-like disorder, Friedreich ataxia, and in AT relatives. The expression pattern of candidate genes was evaluated by RT-qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified and predicted the pathogenicity of novel variants in the\n                      <jats:italic>ATM<\/jats:italic>\n                      gene. Computational analysis suggested that the novel identified missense mutation could affect ATP binding pattern and ATM protein flexibility, while Alu element insertion could probably induces a premature stop codon. Furthermore, our results confirm the pathogenic effect of identified splicing mutations on the ATM transcript. Moreover, we noticed a high percentage of LTCD4\u2009+\u2009and LTCD8\u2009+\u2009senescent subsets in AT patients and a relative increase of the of intermediate and non-classical monocytes accompanied with a decrease of classical monocytes specifically in AT patients with truncated biallelic mutations which was intriguingly similar to the immune profile of AT parents. In addition, a difference of immune pattern was observed between AT patients with biallelic truncated mutations compared to those with at least one non-truncated mutation, with a variability intragroup. Gene expression analysis identified\n                      <jats:italic>FOXO3<\/jats:italic>\n                      ,\n                      <jats:italic>IL33<\/jats:italic>\n                      and\n                      <jats:italic>METTL3<\/jats:italic>\n                      as putative genes that may yield clues into AT pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Taken together, our study expands the mutational spectrum of AT disease worldwide and further characterize the immune profile of AT patients uncovering a possible difference in some immune cellular subsets related to\n                      <jats:italic>ATM<\/jats:italic>\n                      mutation type and delineate putative immune abnormalities related to\n                      <jats:italic>ATM<\/jats:italic>\n                      heterozygosity among AT parents. Furthermore, dysregulation in\n                      <jats:italic>FOXO3<\/jats:italic>\n                      ,\n                      <jats:italic>IL33<\/jats:italic>\n                      and\n                      <jats:italic>METTL3<\/jats:italic>\n                      expression could be related to disease severity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-07871-2","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:24:12Z","timestamp":1771503852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel genetic variants identification and immune profiling in ataxia telangiectasia patients"],"prefix":"10.1186","volume":"24","author":[{"given":"Rim","family":"Jenni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedia","family":"Klaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Chikhaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khouloud","family":"Zayoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Cochet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichraf","family":"Kraoua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydie","family":"Burglen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-4775","authenticated-orcid":false,"given":"Houda","family":"Yacoub-Youssef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"issue":"3","key":"7871_CR1","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/pai.13020","volume":"30","author":"P Amirifar","year":"2019","unstructured":"Amirifar P, Ranjouri MR, Yazdani R, Abolhassani H, Aghamohammadi A. Ataxia-telangiectasia: A review of clinical features and molecular pathology. Pediatr Allergy Immunol. 2019;30(3):277\u201388.","journal-title":"Pediatr Allergy Immunol"},{"issue":"12","key":"7871_CR2","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/s41580-021-00394-2","volume":"22","author":"J-H Lee","year":"2021","unstructured":"Lee J-H, Paull TT. Cellular functions of the protein kinase ATM and their relevance to human disease. Nat Rev Mol Cell Biol. 2021;22(12):796\u2013814.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"9","key":"7871_CR3","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1084\/jem.20041074","volume":"200","author":"JM Lumsden","year":"2004","unstructured":"Lumsden JM, McCarty T, Petiniot LK, Shen R, Barlow C, Wynn TA, et al. Immunoglobulin class switch recombination is impaired in Atm-deficient mice. J Exp Med. 2004;200(9):1111\u201321.","journal-title":"J Exp Med"},{"issue":"12","key":"7871_CR4","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.4161\/cc.10.12.16011","volume":"10","author":"EJ Gapud","year":"2011","unstructured":"Gapud EJ, Sleckman BP. Unique and redundant functions of ATM and DNA-PKcs during V (D) J recombination. Cell Cycle. 2011;10(12):1928\u201335.","journal-title":"Cell Cycle"},{"issue":"6","key":"7871_CR5","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1097\/MPH.0000000000001005","volume":"40","author":"SA Upadhyaya","year":"2018","unstructured":"Upadhyaya SA, Mody R, Walkovich K, Hutchinson RJ, Sandlund JT, Connelly JA. Ataxia telangiectasia and cancer predisposition: challenges in management. J Pediatr Hematol Oncol. 2018;40(6):483\u20136.","journal-title":"J Pediatr Hematol Oncol"},{"issue":"1","key":"7871_CR6","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1186\/s12967-025-06648-3","volume":"23","author":"J Wang","year":"2025","unstructured":"Wang J, Li L, Qin Y, Zhang W. TTI1 contributes to radioresistance by activating ATM pathway in rectal cancer. J Translational Med. 2025;23(1):652.","journal-title":"J Translational Med"},{"issue":"1","key":"7871_CR7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s13023-016-0543-7","volume":"11","author":"C Rothblum-Oviatt","year":"2016","unstructured":"Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM. Ataxia telangiectasia: a review. Orphanet J Rare Dis. 2016;11(1):159.","journal-title":"Orphanet J Rare Dis"},{"key":"7871_CR8","doi-asserted-by":"crossref","unstructured":"Lai J, Demirbas D, Kim J, Jeffries AM, Tolles A, Park J, et al. ATM-deficiency-induced microglial activation promotes neurodegeneration in ataxia-telangiectasia. Cell Rep. 2024;43(1).","DOI":"10.1016\/j.celrep.2023.113622"},{"issue":"2","key":"7871_CR9","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/cei.12262","volume":"176","author":"C Chopra","year":"2014","unstructured":"Chopra C, Davies G, Taylor M, Anderson M, Bainbridge S, Tighe P, et al. Immune deficiency in Ataxia-Telangiectasia: a longitudinal study of 44 patients. Clin Experimental Immunol. 2014;176(2):275\u201382.","journal-title":"Clin Experimental Immunol"},{"issue":"18","key":"7871_CR10","doi-asserted-by":"publisher","first-page":"6041","DOI":"10.3390\/jcm12186041","volume":"12","author":"F Cavone","year":"2023","unstructured":"Cavone F, Cappelli S, Bonuccelli A, D\u2019Elios S, Costagliola G, Peroni D, et al. Ataxia telangiectasia arising as immunodeficiency: the intriguing differential diagnosis. J Clin Med. 2023;12(18):6041.","journal-title":"J Clin Med"},{"key":"7871_CR11","doi-asserted-by":"publisher","first-page":"972952","DOI":"10.3389\/fped.2022.972952","volume":"10","author":"A Szczawi\u0144ska-Pop\u0142onyk","year":"2022","unstructured":"Szczawi\u0144ska-Pop\u0142onyk A, T\u0105polska-J\u00f3\u017awiak K, Schwartzmann E, Pietrucha B. Infections and immune dysregulation in ataxia-telangiectasia children with hyper-IgM and non-hyper-IgM phenotypes: A single-center experience. Front Pead. 2022;10:972952.","journal-title":"Front Pead"},{"issue":"1","key":"7871_CR12","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1046\/j.1365-2249.2002.01830.x","volume":"129","author":"R Schubert","year":"2002","unstructured":"Schubert R, Reichenbach J, Zielen S. Deficiencies in CD4 + and CD8 + T cell subsets in ataxia telangiectasia. Clin Experimental Immunol. 2002;129(1):125\u201332.","journal-title":"Clin Experimental Immunol"},{"key":"7871_CR13","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1007\/BF00918137","volume":"12","author":"R Paganelli","year":"1992","unstructured":"Paganelli R, Scala E, Scarselli E, Ortolani C, Cossarizza A, Carmini D, et al. Selective deficiency of CD4+\/CD45RA+ lymphocytes in patients with ataxia-telangiectasia. J Clin Immunol. 1992;12:84\u201391.","journal-title":"J Clin Immunol"},{"key":"7871_CR14","doi-asserted-by":"publisher","first-page":"108802","DOI":"10.1016\/j.clim.2021.108802","volume":"230","author":"MG Desimio","year":"2021","unstructured":"Desimio MG, Finocchi A, Di Matteo G, Di Cesare S, Giancotta C, Conti F, et al. Altered NK-cell compartment and dysfunctional NKG2D\/NKG2D-ligand axis in patients with ataxia-telangiectasia. Clin Immunol. 2021;230:108802.","journal-title":"Clin Immunol"},{"key":"7871_CR15","doi-asserted-by":"publisher","first-page":"1377955","DOI":"10.3389\/fimmu.2024.1377955","volume":"15","author":"L Graafen","year":"2024","unstructured":"Graafen L, Heinze A, Albinger N, Salzmann-Manrique E, Gan\u00df F, H\u00fcnecke S, et al. Immune profiling and functional analysis of NK and T cells in ataxia telangiectasia. Front Immunol. 2024;15:1377955.","journal-title":"Front Immunol"},{"issue":"1","key":"7871_CR16","doi-asserted-by":"publisher","first-page":"261","DOI":"10.4049\/jimmunol.1101909","volume":"189","author":"EF Carney","year":"2012","unstructured":"Carney EF, Srinivasan V, Moss P, Taylor AM. Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95. J Immunol (Baltimore Md: 1950). 2012;189(1):261\u20138.","journal-title":"J Immunol (Baltimore Md: 1950)"},{"issue":"1","key":"7871_CR17","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.clim.2011.03.007","volume":"140","author":"AR Exley","year":"2011","unstructured":"Exley AR, Buckenham S, Hodges E, Hallam R, Byrd P, Last J, et al. Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia. Clin Immunol (Orlando Fla). 2011;140(1):26\u201336.","journal-title":"Clin Immunol (Orlando Fla)"},{"key":"7871_CR18","doi-asserted-by":"publisher","first-page":"1490302","DOI":"10.3389\/fragi.2024.1490302","volume":"5","author":"MV Wrona","year":"2024","unstructured":"Wrona MV, Ghosh R, Coll K, Chun C, Yousefzadeh MJ. The 3 i\u2019s of immunity and aging: immunosenescence, inflammaging, and immune resilience. Front Aging. 2024;5:1490302.","journal-title":"Front Aging"},{"key":"7871_CR19","doi-asserted-by":"publisher","first-page":"1506165","DOI":"10.3389\/fimmu.2025.1506165","volume":"16","author":"S Basu","year":"2025","unstructured":"Basu S, Ulbricht Y, Rossol M. Healthy and premature aging of monocytes and macrophages. Front Immunol. 2025;16:1506165.","journal-title":"Front Immunol"},{"key":"7871_CR20","doi-asserted-by":"crossref","unstructured":"Zaki-Dizaji M, Akrami SM, Azizi G, Abolhassani H, Aghamohammadi A. Inflammation, a significant player of ataxia-telangiectasia pathogenesis? Inflammation research: official. J Eur Histamine Res Soc. 2018;67(7):559\u201370.","DOI":"10.1007\/s00011-018-1142-y"},{"key":"7871_CR21","doi-asserted-by":"publisher","first-page":"101653","DOI":"10.1016\/j.arr.2022.101653","volume":"79","author":"J Aguado","year":"2022","unstructured":"Aguado J, G\u00f3mez-Incl\u00e1n C, Leeson HC, Lavin MF, Shiloh Y, Wolvetang EJ. The hallmarks of aging in Ataxia-Telangiectasia. Ageing Res Rev. 2022;79:101653.","journal-title":"Ageing Res Rev"},{"key":"7871_CR22","doi-asserted-by":"publisher","first-page":"1636787","DOI":"10.3389\/fnins.2025.1636787","volume":"19","author":"GG Stirparo","year":"2025","unstructured":"Stirparo GG, Xu X, Thompson T, Page K, Harvey JRM, Cadwalladr D, et al. NETSseq reveals inflammatory and aging mechanisms in distinct cell types, driving cerebellar decline in ataxia telangiectasia. Front Neurosci. 2025;19:1636787.","journal-title":"Front Neurosci"},{"issue":"12","key":"7871_CR23","doi-asserted-by":"publisher","first-page":"e0209496","DOI":"10.1371\/journal.pone.0209496","volume":"13","author":"SA McGrath-Morrow","year":"2018","unstructured":"McGrath-Morrow SA, Ndeh R, Collaco JM, Rothblum-Oviatt C, Wright J, O\u2019Reilly MA, et al. Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia. PLoS ONE. 2018;13(12):e0209496.","journal-title":"PLoS ONE"},{"issue":"3","key":"7871_CR24","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1002\/humu.22016","volume":"33","author":"MM Verhagen","year":"2012","unstructured":"Verhagen MM, Last JI, Hogervorst FB, Smeets DF, Roeleveld N, Verheijen F, et al. Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: A genotype\u2013phenotype study. Hum Mutat. 2012;33(3):561\u201371.","journal-title":"Hum Mutat"},{"issue":"3","key":"7871_CR25","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/cge.12453","volume":"87","author":"A Taylor","year":"2015","unstructured":"Taylor A, Lam Z, Last J, Byrd P. Ataxia telangiectasia: more variation at clinical and cellular levels. Clin Genet. 2015;87(3):199\u2013208.","journal-title":"Clin Genet"},{"issue":"2","key":"7871_CR26","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1111\/j.1365-2249.2008.03684.x","volume":"153","author":"ER Staples","year":"2008","unstructured":"Staples ER, McDermott EM, Reiman A, Byrd PJ, Ritchie S, Taylor AM, et al. Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene. Clin Exp Immunol. 2008;153(2):214\u201320.","journal-title":"Clin Exp Immunol"},{"issue":"4","key":"7871_CR27","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1007\/s10875-022-01234-4","volume":"42","author":"E Cirillo","year":"2022","unstructured":"Cirillo E, Polizzi A, Soresina A, Prencipe R, Giardino G, Cancrini C, et al. Progressive depletion of B and T lymphocytes in patients with ataxia telangiectasia: results of the Italian primary immunodeficiency network. J Clin Immunol. 2022;42(4):783\u201397.","journal-title":"J Clin Immunol"},{"issue":"4","key":"7871_CR28","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/s12185-009-0408-0","volume":"90","author":"T Morio","year":"2009","unstructured":"Morio T, Takahashi N, Watanabe F, Honda F, Sato M, Takagi M, et al. Phenotypic variations between affected siblings with ataxia-telangiectasia: ataxia-telangiectasia in Japan. Int J Hematol. 2009;90(4):455\u201362.","journal-title":"Int J Hematol"},{"issue":"5","key":"7871_CR29","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1136\/jmedgenet-2018-105635","volume":"56","author":"NJH van Os","year":"2019","unstructured":"van Os NJH, Chessa L, Weemaes CMR, van Deuren M, Fi\u00e9vet A, van Gaalen J, et al. Genotype-phenotype correlations in ataxia telangiectasia patients with ATM c.3576G > A and c.8147T > C mutations. J Med Genet. 2019;56(5):308\u201316.","journal-title":"J Med Genet"},{"issue":"2","key":"7871_CR30","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1111\/cge.12710","volume":"90","author":"NJ van Os","year":"2016","unstructured":"van Os NJ, Roeleveld N, Weemaes CM, Jongmans MC, Janssens G, Taylor AMR, et al. Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta\u2010analysis and evidence\u2010based guideline. Clin Genet. 2016;90(2):105\u201317.","journal-title":"Clin Genet"},{"issue":"3","key":"7871_CR31","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1667\/0033-7587(2002)157[0312:ROATAN]2.0.CO;2","volume":"157","author":"S Neubauer","year":"2002","unstructured":"Neubauer S, Arutyunyan R, Stumm M, D\u00f6rk T, Bendix R, Bremer M, et al. Radiosensitivity of ataxia telangiectasia and Nijmegen breakage syndrome homozygotes and heterozygotes as determined by three-color FISH chromosome painting. Radiat Res. 2002;157(3):312\u201321.","journal-title":"Radiat Res"},{"issue":"2","key":"7871_CR32","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/BF00286705","volume":"83","author":"MP Rosin","year":"1989","unstructured":"Rosin MP, Ochs HD, Gatti RA, Boder E. Heterogeneity of chromosomal breakage levels in epithelial tissue of ataxia-telangiectasia homozygotes and heterozygotes. Hum Genet. 1989;83(2):133\u20138.","journal-title":"Hum Genet"},{"issue":"2","key":"7871_CR33","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/pai.13387","volume":"32","author":"I Ogulur","year":"2021","unstructured":"Ogulur I, Ertuzun T, Kocamis B, Kendir Demirkol Y, Uyar E, Kiykim A, et al. Parents of ataxia-telangiectasia patients display a distinct cellular immune phenotype mimicking ATM\u2010mutated patients. Pediatr Allergy Immunol. 2021;32(2):349\u201357.","journal-title":"Pediatr Allergy Immunol"},{"issue":"1","key":"7871_CR34","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1002\/mdc3.13110","volume":"8","author":"IR Raslan","year":"2021","unstructured":"Raslan IR, de Assis Pereira Matos PCA, Boaratti Ciarlariello V, Daghastanli KH, Rosa ABR, Arita JH, et al. Beyond typical ataxia telangiectasia: how to identify the ataxia telangiectasia-like disorders. Mov Disorders Clin Pract. 2021;8(1):118\u201325.","journal-title":"Mov Disorders Clin Pract"},{"key":"7871_CR35","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s40673-017-0062-x","volume":"4","author":"K B\u00fcrk","year":"2017","unstructured":"B\u00fcrk K. Friedreich ataxia: current status and future prospects. Cerebellum Ataxias. 2017;4:4.","journal-title":"Cerebellum Ataxias"},{"issue":"5","key":"7871_CR36","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.3390\/ijms23052580","volume":"23","author":"O Pansarasa","year":"2022","unstructured":"Pansarasa O, Garofalo M, Scarian E, Dragoni F, Garau J, Di Gerlando R, et al. Biomarkers in human peripheral blood mononuclear cells: the state of the Art in amyotrophic lateral sclerosis. Int J Mol Sci. 2022;23(5):2580.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"7871_CR37","doi-asserted-by":"publisher","first-page":"29","DOI":"10.21037\/atm-21-4974","volume":"10","author":"X Wang","year":"2022","unstructured":"Wang X, Wang D, Su F, Li C, Chen M. Immune abnormalities and differential gene expression in the hippocampus and peripheral blood of patients with alzheimer\u2019s disease. Annals Translational Med. 2022;10(2):29.","journal-title":"Annals Translational Med"},{"issue":"2","key":"7871_CR38","doi-asserted-by":"publisher","first-page":"100173","DOI":"10.1016\/j.mocell.2024.100173","volume":"48","author":"MS Lee","year":"2025","unstructured":"Lee MS, Kim JW, Park DG, Heo H, Kim J, Yoon JH, et al. Autophagic signatures in peripheral blood mononuclear cells from parkinson\u2019s disease patients. Mol Cells. 2025;48(2):100173.","journal-title":"Mol Cells"},{"issue":"1","key":"7871_CR39","doi-asserted-by":"publisher","first-page":"7479","DOI":"10.1038\/s41598-020-64514-2","volume":"10","author":"SA McGrath-Morrow","year":"2020","unstructured":"McGrath-Morrow SA, Ndeh R, Helmin KA, Khuder B, Rothblum-Oviatt C, Collaco JM, et al. DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype. Sci Rep. 2020;10(1):7479.","journal-title":"Sci Rep"},{"issue":"1","key":"7871_CR40","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13023-024-03073-5","volume":"19","author":"SN Michki","year":"2024","unstructured":"Michki SN, Singer BD, Perez JV, Thomas AJ, Natale V, Helmin KA, et al. Transcriptional profiling of peripheral blood mononuclear cells identifies inflammatory phenotypes in ataxia telangiectasia. Orphanet J Rare Dis. 2024;19(1):67.","journal-title":"Orphanet J Rare Dis"},{"key":"7871_CR41","doi-asserted-by":"crossref","unstructured":"Micol R, Ben Slama L, Suarez F, Le Mignot L, Beaut\u00e9 J, Mahlaoui N, et al. Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J Allergy Clin Immunol. 2011;128(2):382-9.e1.","DOI":"10.1016\/j.jaci.2011.03.052"},{"issue":"W1","key":"7871_CR42","doi-asserted-by":"publisher","first-page":"W338","DOI":"10.1093\/nar\/gky356","volume":"46","author":"A Kuriata","year":"2018","unstructured":"Kuriata A, Gierut AM, Oleniecki T, Ciemny MP, Kolinski A, Kurcinski M, et al. CABS-flex 2.0: a web server for fast simulations of flexibility of protein structures. Nucleic Acids Res. 2018;46(W1):W338\u201343.","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"7871_CR43","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1182\/blood-2014-03-559542","volume":"124","author":"MJ Kiel","year":"2014","unstructured":"Kiel MJ, Velusamy T, Rolland D, Sahasrabuddhe AA, Chung F, Bailey NG, et al. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia. Blood. 2014;124(9):1460\u201372.","journal-title":"Blood"},{"issue":"Pt 1","key":"7871_CR44","doi-asserted-by":"publisher","first-page":"134444","DOI":"10.1016\/j.ijbiomac.2024.134444","volume":"278","author":"R Jenni","year":"2024","unstructured":"Jenni R, Klaa H, Khamessi O, Chikhaoui A, Najjar D, Ghedira K, et al. Clinical and genetic spectrum of ataxia telangiectasia Tunisian patients: bioinformatic analysis unveil mechanisms of ATM variants pathogenicity. Int J Biol Macromol. 2024;278(Pt 1):134444.","journal-title":"Int J Biol Macromol"},{"key":"7871_CR45","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1750-1172-1-47","volume":"1","author":"F Palau","year":"2006","unstructured":"Palau F, Espin\u00f3s C. Autosomal recessive cerebellar ataxias. Orphanet J Rare Dis. 2006;1:47.","journal-title":"Orphanet J Rare Dis"},{"issue":"8","key":"7871_CR46","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/sj.embor.7400210","volume":"5","author":"PJ McKinnon","year":"2004","unstructured":"McKinnon PJ. ATM and ataxia telangiectasia. EMBO Rep. 2004;5(8):772\u20136.","journal-title":"EMBO Rep"},{"key":"7871_CR47","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.neulet.2015.11.036","volume":"611","author":"XL Liu","year":"2016","unstructured":"Liu XL, Wang T, Huang XJ, Zhou HY, Luan XH, Shen JY, et al. Novel ATM mutations with ataxia-telangiectasia. Neurosci Lett. 2016;611:112\u20135.","journal-title":"Neurosci Lett"},{"issue":"7","key":"7871_CR48","doi-asserted-by":"publisher","first-page":"531","DOI":"10.2174\/1389202920666191107153734","volume":"20","author":"M Heidari","year":"2019","unstructured":"Heidari M, Soleyman-Nejad M, Taskhiri MH, Shahpouri J, Isazadeh A, Ahangari R, et al. Identification of two novel mutations in the ATM gene from patients with Ataxia-Telangiectasia by whole exome sequencing. Curr Genom. 2019;20(7):531\u20134.","journal-title":"Curr Genom"},{"issue":"2","key":"7871_CR49","first-page":"187","volume":"24","author":"M Badalzadeh","year":"2025","unstructured":"Badalzadeh M, Soleimani Bavani M, Alizadeh Z, Mirmoghtadaei M, Shakerian L, Bahram S, et al. Clinical characterization and mutation analysis of 13 Iranian ataxia telangiectasia patients: introducing two novel mutations. Iran J Allergy Asthma Immunol. 2025;24(2):187\u201397.","journal-title":"Iran J Allergy Asthma Immunol"},{"key":"7871_CR50","doi-asserted-by":"publisher","first-page":"1228810","DOI":"10.3389\/fneur.2023.1228810","volume":"14","author":"L Shao","year":"2023","unstructured":"Shao L, Wang H, Xu J, Qi M, Yu Z, Zhang J. Ataxia-telangiectasia in china: a case report of a novel ATM variant and literature review. Front Neurol. 2023;14:1228810.","journal-title":"Front Neurol"},{"issue":"3","key":"7871_CR51","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/cge.12453","volume":"87","author":"AM Taylor","year":"2015","unstructured":"Taylor AM, Lam Z, Last JI, Byrd PJ. Ataxia telangiectasia: more variation at clinical and cellular levels. Clin Genet. 2015;87(3):199\u2013208.","journal-title":"Clin Genet"},{"key":"7871_CR52","doi-asserted-by":"publisher","first-page":"134444","DOI":"10.1016\/j.ijbiomac.2024.134444","volume":"278","author":"R Jenni","year":"2024","unstructured":"Jenni R, Klaa H, Khamessi O, Chikhaoui A, Najjar D, Ghedira K, et al. Clinical and genetic spectrum of ataxia telangiectasia Tunisian patients: bioinformatic analysis unveil mechanisms of ATM variants pathogenicity. Int J Biol Macromol. 2024;278:134444.","journal-title":"Int J Biol Macromol"},{"key":"7871_CR53","doi-asserted-by":"publisher","first-page":"1344018","DOI":"10.3389\/fneur.2024.1344018","volume":"15","author":"N Ammous-Boukhris","year":"2024","unstructured":"Ammous-Boukhris N, Abdelmaksoud-Dammak R, Ben Ayed-Guerfali D, Guidara S, Jallouli O, Kamoun H, et al. Case report: compound heterozygous variants detected by next-generation sequencing in a Tunisian child with ataxia-telangiectasia. Front Neurol. 2024;15:1344018.","journal-title":"Front Neurol"},{"issue":"1","key":"7871_CR54","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.jaci.2018.05.028","volume":"143","author":"A Berland","year":"2019","unstructured":"Berland A, Rosain J, Kaltenbach S, Allain V, Mahlaoui N, Melki I, et al. PROMIDIS\u03b1: A T-cell receptor \u03b1 signature associated with immunodeficiencies caused by V(D)J recombination defects. J Allergy Clin Immunol. 2019;143(1):325\u2013e342.","journal-title":"J Allergy Clin Immunol"},{"key":"7871_CR55","doi-asserted-by":"crossref","unstructured":"Toss A, Tenedini E, Piombino C, Venturelli M, Marchi I, Gasparini E, et al. Clinicopathologic profile of breast cancer in germline ATM and CHEK2 mutation carriers. Genes. 2021;12(5).","DOI":"10.3390\/genes12050616"},{"issue":"Pt 5","key":"7871_CR56","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1111\/j.1469-1809.2009.00535.x","volume":"73","author":"L Chessa","year":"2009","unstructured":"Chessa L, Piane M, Magliozzi M, Torrente I, Savio C, Lulli P, et al. Founder effects for ATM gene mutations in Italian ataxia telangiectasia families. Ann Hum Genet. 2009;73(Pt 5):532\u20139.","journal-title":"Ann Hum Genet"},{"issue":"5","key":"7871_CR57","doi-asserted-by":"publisher","first-page":"e1700933","DOI":"10.1126\/sciadv.1700933","volume":"3","author":"D Bareti\u0107","year":"2017","unstructured":"Bareti\u0107 D, Pollard HK, Fisher DI, Johnson CM, Santhanam B, Truman CM, et al. Structures of closed and open conformations of dimeric human ATM. Sci Adv. 2017;3(5):e1700933.","journal-title":"Sci Adv"},{"issue":"4","key":"7871_CR58","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.bbrc.2014.09.038","volume":"452","author":"F Du","year":"2014","unstructured":"Du F, Zhang M, Li X, Yang C, Meng H, Wang D, et al. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair. Biochem Biophys Res Commun. 2014;452(4):1034\u20139.","journal-title":"Biochem Biophys Res Commun"},{"issue":"39","key":"7871_CR59","doi-asserted-by":"publisher","first-page":"eadi8291","DOI":"10.1126\/sciadv.adi8291","volume":"9","author":"AC Howes","year":"2023","unstructured":"Howes AC, Perisic O, Williams RL. Structural insights into the activation of ataxia-telangiectasia mutated by oxidative stress. Sci Adv. 2023;9(39):eadi8291.","journal-title":"Sci Adv"},{"key":"7871_CR60","doi-asserted-by":"publisher","first-page":"6623515","DOI":"10.1155\/2023\/6623515","volume":"2023","author":"J Klein","year":"2023","unstructured":"Klein J, Allister AB, Schmidt G, Otto A, Heinecke K, Bax-Knoche J, et al. A novel Alu element insertion in ATM induces exon skipping in suspected HBOC patients. Hum Mutat. 2023;2023:6623515.","journal-title":"Hum Mutat"},{"issue":"2","key":"7871_CR61","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41431-023-01478-7","volume":"32","author":"R Wijngaard","year":"2024","unstructured":"Wijngaard R, Demidov G, O\u2019Gorman L, Corominas-Galbany J, Yaldiz B, Steyaert W, et al. Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples. Eur J Hum Genet EJHG. 2024;32(2):200\u20138.","journal-title":"Eur J Hum Genet EJHG"},{"issue":"11","key":"7871_CR62","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1016\/j.ajhg.2023.09.008","volume":"110","author":"B Zhao","year":"2023","unstructured":"Zhao B, Nguyen MA, Woo S, Kim J, Yu TW, Lee EA. Contribution and therapeutic implications of retroelement insertions in ataxia telangiectasia. Am J Hum Genet. 2023;110(11):1976\u201382.","journal-title":"Am J Hum Genet"},{"issue":"21","key":"7871_CR63","doi-asserted-by":"publisher","first-page":"5498","DOI":"10.3390\/cancers13215498","volume":"13","author":"S Putti","year":"2021","unstructured":"Putti S, Giovinazzo A, Merolle M, Falchetti ML, Pellegrini M. ATM kinase dead: from ataxia telangiectasia syndrome to cancer. Cancers. 2021;13(21):5498.","journal-title":"Cancers"},{"issue":"2","key":"7871_CR64","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/bjc.2011.534","volume":"106","author":"PJ Byrd","year":"2012","unstructured":"Byrd PJ, Srinivasan V, Last JI, Smith A, Biggs P, Carney EF, et al. Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia. Br J Cancer. 2012;106(2):262\u20138.","journal-title":"Br J Cancer"},{"issue":"8","key":"7871_CR65","doi-asserted-by":"publisher","first-page":"102247","DOI":"10.1016\/j.jbc.2022.102247","volume":"298","author":"C Arter","year":"2022","unstructured":"Arter C, Trask L, Ward S, Yeoh S, Bayliss R. Structural features of the protein kinase domain and targeted binding by small-molecule inhibitors. J Biol Chem. 2022;298(8):102247.","journal-title":"J Biol Chem"},{"issue":"15","key":"7871_CR66","first-page":"2150","volume":"30","author":"M Jamroz","year":"2014","unstructured":"Jamroz M, Kolinski A, Kmiecik S. CABS-flex predictions of protein flexibility compared with NMR ensembles. Bioinf (Oxford England). 2014;30(15):2150\u20134.","journal-title":"Bioinf (Oxford England)"},{"issue":"1","key":"7871_CR67","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1021\/ct300854w","volume":"9","author":"M Jamroz","year":"2013","unstructured":"Jamroz M, Orozco M, Kolinski A, Kmiecik S. Consistent view of protein fluctuations from All-Atom molecular dynamics and Coarse-Grained dynamics with Knowledge-Based Force-Field. J Chem Theory Comput. 2013;9(1):119\u201325.","journal-title":"J Chem Theory Comput"},{"issue":"9","key":"7871_CR68","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/S0929-693X(97)88145-6","volume":"4","author":"M Bejaoui","year":"1997","unstructured":"Bejaoui M, Barbouche MR, Sassi A, Larguche B, Miladi N, Bouguerra A, et al. Les d\u00e9ficits immunitaires primitifs En tunisie: \u00e9tude de 152 Cas. Archives De P\u00e9diatrie. 1997;4(9):827\u201331.","journal-title":"Archives De P\u00e9diatrie"},{"key":"7871_CR69","doi-asserted-by":"publisher","first-page":"686333","DOI":"10.3389\/fimmu.2021.686333","volume":"12","author":"TJ Weitering","year":"2021","unstructured":"Weitering TJ, Melsen JE, van Ostaijen-Ten Dam MM, Weemaes CMR, van der Schilham MW. Normal numbers of stem cell memory T cells despite strongly reduced Naive T cells support intact memory T cell compartment in ataxia telangiectasia. Front Immunol. 2021;12:686333.","journal-title":"Front Immunol"},{"key":"7871_CR70","unstructured":"Veenhuis S, van Os N, Weemaes C, Kamsteeg E-J, Willemsen M. Ataxia-telangiectasia. 2016."},{"key":"7871_CR71","doi-asserted-by":"crossref","unstructured":"Zayoud K, Chikhaoui A, Kraoua I, Tebourbi A, Najjar D, Ayari S, et al. Immunity in the progeroid model of Cockayne syndrome: biomarkers of pathological aging. Cells. 2024;13(5).","DOI":"10.3390\/cells13050402"},{"issue":"1","key":"7871_CR72","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41392-023-01451-2","volume":"8","author":"Z Liu","year":"2023","unstructured":"Liu Z, Liang Q, Ren Y, Guo C, Ge X, Wang L, et al. Immunosenescence: molecular mechanisms and diseases. Signal Transduct Target Therapy. 2023;8(1):200.","journal-title":"Signal Transduct Target Therapy"},{"issue":"1","key":"7871_CR73","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1046\/j.1365-2249.2002.01830.x","volume":"129","author":"R Schubert","year":"2002","unstructured":"Schubert R, Reichenbach J, Zielen S. Deficiencies in CD4 + and CD8 + T cell subsets in ataxia telangiectasia. Clin Exp Immunol. 2002;129(1):125\u201332.","journal-title":"Clin Exp Immunol"},{"issue":"4","key":"7871_CR74","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/j.arr.2013.04.003","volume":"12","author":"J Hazeldine","year":"2013","unstructured":"Hazeldine J, Lord JM. The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev. 2013;12(4):1069\u201378.","journal-title":"Ageing Res Rev"},{"issue":"4","key":"7871_CR75","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s00262-016-1803-z","volume":"65","author":"H Kared","year":"2016","unstructured":"Kared H, Martelli S, Ng TP, Pender SL, Larbi A. CD57 in human natural killer cells and T-lymphocytes. Cancer Immunol Immunother. 2016;65(4):441\u201352.","journal-title":"Cancer Immunol Immunother"},{"key":"7871_CR76","first-page":"63","volume-title":"Phenotypic and functional alterations of monocyte subsets with aging","author":"Y Cao","year":"2022","unstructured":"Cao Y, Fan Y, Li F, Hao Y, Kong Y, Chen C, et al. Phenotypic and functional alterations of monocyte subsets with aging. Volume 19. Immunity & ageing: I & A; 2022. p. 63. 1."},{"issue":"4","key":"7871_CR77","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.coi.2010.05.003","volume":"22","author":"AC Shaw","year":"2010","unstructured":"Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM. Aging of the innate immune system. Curr Opin Immunol. 2010;22(4):507\u201313.","journal-title":"Curr Opin Immunol"},{"key":"7871_CR78","doi-asserted-by":"crossref","unstructured":"Brauning A, Rae M, Zhu G, Fulton E, Admasu TD, Stolzing A, et al. Aging of the immune system: focus on natural killer cells phenotype and functions. Cells. 2022;11(6).","DOI":"10.3390\/cells11061017"},{"issue":"1","key":"7871_CR79","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1055\/s-2008-1076736","volume":"39","author":"A Soresina","year":"2008","unstructured":"Soresina A, Meini A, Lougaris V, Cattaneo G, Pellegrino S, Piane M, et al. Different clinical and immunological presentation of ataxia-telangiectasia within the same family. Neuropediatrics. 2008;39(1):43\u20135.","journal-title":"Neuropediatrics"},{"issue":"1","key":"7871_CR80","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1093\/bmb\/ldx034","volume":"124","author":"A Cook","year":"2017","unstructured":"Cook A, Giunti P. Friedreich\u2019s ataxia: clinical features, pathogenesis and management. Br Med Bull. 2017;124(1):19\u201330.","journal-title":"Br Med Bull"},{"issue":"7","key":"7871_CR81","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1242\/dmm.024711","volume":"9","author":"D Carrero","year":"2016","unstructured":"Carrero D, Soria-Valles C, L\u00f3pez-Ot\u00edn C. Hallmarks of progeroid syndromes: lessons from mice and reprogrammed cells. Dis Models Mech. 2016;9(7):719\u201335.","journal-title":"Dis Models Mech"},{"issue":"3","key":"7871_CR82","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.jpeds.2009.02.037","volume":"155","author":"N Uchisaka","year":"2009","unstructured":"Uchisaka N, Takahashi N, Sato M, Kikuchi A, Mochizuki S, Imai K, et al. Two brothers with ataxia-telangiectasia-like disorder with lung adenocarcinoma. J Pediatr. 2009;155(3):435\u20138.","journal-title":"J Pediatr"},{"issue":"25","key":"7871_CR83","doi-asserted-by":"publisher","first-page":"5146","DOI":"10.1093\/hmg\/ddt368","volume":"22","author":"JA Regal","year":"2013","unstructured":"Regal JA, Festerling TA, Buis JM, Ferguson DO. Disease-associated MRE11 mutants impact ATM\/ATR DNA damage signaling by distinct mechanisms. Hum Mol Genet. 2013;22(25):5146\u201359.","journal-title":"Hum Mol Genet"},{"issue":"6","key":"7871_CR84","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1097\/PPO.0000000000000002","volume":"19","author":"T Maj","year":"2013","unstructured":"Maj T, Wei S, Welling T, Zou W. T cells and costimulation in cancer. Cancer J (Sudbury Mass). 2013;19(6):473\u201382.","journal-title":"Cancer J (Sudbury Mass)"},{"issue":"17","key":"7871_CR85","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1093\/hmg\/ddy198","volume":"27","author":"D Nachun","year":"2018","unstructured":"Nachun D, Gao F, Isaacs C, Strawser C, Yang Z, Dokuru D, et al. Peripheral blood gene expression reveals an inflammatory transcriptomic signature in friedreich\u2019s ataxia patients. Hum Mol Genet. 2018;27(17):2965\u201377.","journal-title":"Hum Mol Genet"},{"key":"7871_CR86","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.3389\/fnins.2019.01054","volume":"13","author":"D Pathak","year":"2019","unstructured":"Pathak D, Srivastava AK, Padma M, Gulati S, Rajeswari MR. Quantitative proteomic and network analysis of differentially expressed proteins in PBMC of friedreich\u2019s ataxia (FRDA) patients. Front NeuroSci. 2019;13:1054.","journal-title":"Front NeuroSci"},{"key":"7871_CR87","doi-asserted-by":"publisher","first-page":"1202152","DOI":"10.3389\/fragi.2023.1202152","volume":"4","author":"L Kell","year":"2023","unstructured":"Kell L, Simon AK, Alsaleh G, Cox LS. The central role of DNA damage in Immunosenescence. Front Aging. 2023;4:1202152.","journal-title":"Front Aging"},{"key":"7871_CR88","doi-asserted-by":"crossref","unstructured":"Vallejo AN, Brandes JC, Weyand CM, Goronzy JJ. Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence. J Immunol (Baltimore, Md: 1950). 1999;162(11):6572-9.","DOI":"10.4049\/jimmunol.162.11.6572"},{"key":"7871_CR89","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3389\/fimmu.2013.00107","volume":"4","author":"MA Moro-Garc\u00eda","year":"2013","unstructured":"Moro-Garc\u00eda MA, Alonso-Arias R, L\u00f3pez-Larrea C. When aging reaches CD4 + T-Cells: phenotypic and functional changes. Front Immunol. 2013;4:107.","journal-title":"Front Immunol"},{"key":"7871_CR90","doi-asserted-by":"publisher","first-page":"111807","DOI":"10.1016\/j.intimp.2024.111807","volume":"131","author":"Y Guan","year":"2024","unstructured":"Guan Y, Cao M, Wu X, Yan J, Hao Y, Zhang C. CD28null T cells in aging and diseases: from biology to assessment and intervention. Int Immunopharmacol. 2024;131:111807.","journal-title":"Int Immunopharmacol"},{"issue":"25","key":"7871_CR91","doi-asserted-by":"publisher","first-page":"2883","DOI":"10.1161\/01.CIR.101.25.2883","volume":"101","author":"G Liuzzo","year":"2000","unstructured":"Liuzzo G, Goronzy JJ, Yang H, Kopecky SL, Holmes DR, Frye RL, et al. Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation. 2000;101(25):2883\u20138.","journal-title":"Circulation"},{"issue":"10","key":"7871_CR92","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1093\/eurheartj\/ehq499","volume":"32","author":"S Giubilato","year":"2011","unstructured":"Giubilato S, Liuzzo G, Brugaletta S, Pitocco D, Graziani F, Smaldone C, et al. Expansion of CD4 + CD28null T-lymphocytes in diabetic patients: exploring new pathogenetic mechanisms of increased cardiovascular risk in diabetes mellitus. Eur Heart J. 2011;32(10):1214\u201326.","journal-title":"Eur Heart J"},{"issue":"2","key":"7871_CR93","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/pai.13387","volume":"32","author":"I Ogulur","year":"2021","unstructured":"Ogulur I, Ertuzun T, Kocamis B, Kendir Demirkol Y, Uyar E, Kiykim A, et al. Parents of ataxia-telangiectasia patients display a distinct cellular immune phenotype mimicking ATM-mutated patients. Pediatr Allergy Immunol. 2021;32(2):349\u201357.","journal-title":"Pediatr Allergy Immunol"},{"issue":"3","key":"7871_CR94","doi-asserted-by":"publisher","first-page":"113896","DOI":"10.1016\/j.celrep.2024.113896","volume":"43","author":"PR Woolley","year":"2024","unstructured":"Woolley PR, Wen X, Conway OM, Ender NA, Lee JH, Paull TT. Regulation of transcription patterns, poly(ADP-ribose), and RNA-DNA hybrids by the ATM protein kinase. Cell Rep. 2024;43(3):113896.","journal-title":"Cell Rep"},{"key":"7871_CR95","doi-asserted-by":"crossref","unstructured":"Watters DJ. Oxidative stress in ataxia telangiectasia. Redox report: communications in free radical research. 2003;8(1):23\u20139.","DOI":"10.1179\/135100003125001206"},{"key":"7871_CR96","doi-asserted-by":"crossref","unstructured":"Pozzobon D, Bellezza A, Giorgi FM. Pan-Cancer upregulation of the FOXM1 transcription factor. Genes. 2025;16(1).","DOI":"10.3390\/genes16010056"},{"issue":"3","key":"7871_CR97","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.leukres.2014.12.005","volume":"39","author":"\u00d6 T\u00fcfek\u00e7i","year":"2015","unstructured":"T\u00fcfek\u00e7i \u00d6, Yand\u0131m MK, \u00d6ren H, \u0130rken G, Baran Y. Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line. Leuk Res. 2015;39(3):342\u20137.","journal-title":"Leuk Res"},{"issue":"1","key":"7871_CR98","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13058-023-01675-8","volume":"25","author":"BS Katzenellenbogen","year":"2023","unstructured":"Katzenellenbogen BS, Guillen VS, Katzenellenbogen JA. Targeting the oncogenic transcription factor FOXM1 to improve outcomes in all subtypes of breast cancer. Breast Cancer Res. 2023;25(1):76.","journal-title":"Breast Cancer Res"},{"key":"7871_CR99","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.nicl.2015.08.007","volume":"9","author":"I Sahama","year":"2015","unstructured":"Sahama I, Sinclair K, Fiori S, Doecke J, Pannek K, Reid L, et al. Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study. NeuroImage Clin. 2015;9:206\u201315.","journal-title":"NeuroImage Clin"},{"issue":"1\u20132","key":"7871_CR100","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s00109-022-02281-5","volume":"101","author":"VS Bernardo","year":"2023","unstructured":"Bernardo VS, Torres FF, da Silva DGH. FoxO3 and oxidative stress: a multifaceted role in cellular adaptation. J Mol Med. 2023;101(1\u20132):83\u201399.","journal-title":"J Mol Med"},{"issue":"1","key":"7871_CR101","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/s41580-023-00649-0","volume":"25","author":"MJ Rodriguez-Colman","year":"2024","unstructured":"Rodriguez-Colman MJ, Dansen TB, Burgering BMT. FOXO transcription factors as mediators of stress adaptation. Nat Rev Mol Cell Biol. 2024;25(1):46\u201364.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"7871_CR102","doi-asserted-by":"crossref","unstructured":"Fasano C, Disciglio V, Bertora S, Lepore Signorile M, Simone C. FOXO3a from the nucleus to the mitochondria: a round trip in cellular stress response. Cells. 2019;8(9).","DOI":"10.3390\/cells8091110"},{"issue":"4","key":"7871_CR103","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/ncb1709","volume":"10","author":"WB Tsai","year":"2008","unstructured":"Tsai WB, Chung YM, Takahashi Y, Xu Z, Hu MC. Functional interaction between FOXO3a and ATM regulates DNA damage response. Nat Cell Biol. 2008;10(4):460\u20137.","journal-title":"Nat Cell Biol"},{"issue":"37","key":"7871_CR104","doi-asserted-by":"publisher","first-page":"25692","DOI":"10.1074\/jbc.M800517200","volume":"283","author":"S Yalcin","year":"2008","unstructured":"Yalcin S, Zhang X, Luciano JP, Mungamuri SK, Marinkovic D, Vercherat C, et al. Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. J Biol Chem. 2008;283(37):25692\u2013705.","journal-title":"J Biol Chem"},{"issue":"9","key":"7871_CR105","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1242\/jcs.185009","volume":"129","author":"C Shi","year":"2016","unstructured":"Shi C, Viccaro K, Lee HG, Shah K. Cdk5-Foxo3 axis: initially neuroprotective, eventually neurodegenerative in alzheimer\u2019s disease models. J Cell Sci. 2016;129(9):1815\u201330.","journal-title":"J Cell Sci"},{"issue":"6","key":"7871_CR106","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1093\/hmg\/ddt530","volume":"23","author":"E Pino","year":"2014","unstructured":"Pino E, Amamoto R, Zheng L, Cacquevel M, Sarria JC, Knott GW, et al. FOXO3 determines the accumulation of \u03b1-synuclein and controls the fate of dopaminergic neurons in the substantia Nigra. Hum Mol Genet. 2014;23(6):1435\u201352.","journal-title":"Hum Mol Genet"},{"key":"7871_CR107","doi-asserted-by":"crossref","unstructured":"Kim ME, Kim DH, Lee JS. FoxO transcription factors: applicability as a novel immune cell regulators and therapeutic targets in oxidative stress-related diseases. Int J Mol Sci. 2022;23(19).","DOI":"10.3390\/ijms231911877"},{"issue":"3","key":"7871_CR108","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1089\/15230860260196254","volume":"4","author":"J Reichenbach","year":"2002","unstructured":"Reichenbach J, Schubert R, Schindler D, M\u00fcller K, B\u00f6hles H, Zielen S. Elevated oxidative stress in patients with ataxia telangiectasia. Antioxid Redox Signal. 2002;4(3):465\u20139.","journal-title":"Antioxid Redox Signal"},{"key":"7871_CR109","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.molimm.2024.12.001","volume":"177","author":"Z Wang","year":"2025","unstructured":"Wang Z, Sun S, Huang L, Chen X, Xu H, Ma H, et al. METTL3\/YTHDF1-mediated m(6)A modification stabilizes USP12 to deubiquitinate FOXO3 and promote apoptosis in sepsis-induced myocardial dysfunction. Mol Immunol. 2025;177:17\u201331.","journal-title":"Mol Immunol"},{"issue":"3","key":"7871_CR110","first-page":"470","volume":"45","author":"X Zhang","year":"2025","unstructured":"Zhang X, Yang J, Wen Y, Liu Q, Dou L, Gao C. [METTL3-mediated m(6)A modification promotes FOXO3 expression and anthracycline resistance in acute myeloid leukemia cells through autophagy regulation]. J South Med Univ. 2025;45(3):470\u20138.","journal-title":"J South Med Univ"},{"issue":"1","key":"7871_CR111","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.tips.2023.11.002","volume":"45","author":"J Cerneckis","year":"2024","unstructured":"Cerneckis J, Ming GL, Song H, He C, Shi Y. The rise of epitranscriptomics: recent developments and future directions. Trends Pharmacol Sci. 2024;45(1):24\u201338.","journal-title":"Trends Pharmacol Sci"},{"issue":"3","key":"7871_CR112","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.molcel.2020.06.017","volume":"79","author":"C Zhang","year":"2020","unstructured":"Zhang C, Chen L, Peng D, Jiang A, He Y, Zeng Y, et al. METTL3 and N6-Methyladenosine promote homologous Recombination-Mediated repair of DSBs by modulating DNA-RNA hybrid accumulation. Mol Cell. 2020;79(3):425\u2013e427.","journal-title":"Mol Cell"},{"issue":"23","key":"7871_CR113","doi-asserted-by":"publisher","first-page":"7041","DOI":"10.7150\/jca.64061","volume":"12","author":"X Zhang","year":"2021","unstructured":"Zhang X, Liu P, Zheng X, Wang J, Peng Q, Li Z, et al. N6-methyladenosine regulates ATM expression and downstream signaling. J Cancer. 2021;12(23):7041\u201351.","journal-title":"J Cancer"},{"key":"7871_CR114","doi-asserted-by":"publisher","first-page":"555372","DOI":"10.3389\/fmolb.2020.555372","volume":"7","author":"G Dermentzaki","year":"2020","unstructured":"Dermentzaki G, Lotti F. New insights on the role of N (6)-Methyladenosine RNA methylation in the physiology and pathology of the nervous system. Front Mol Biosci. 2020;7:555372.","journal-title":"Front Mol Biosci"},{"key":"7871_CR115","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3389\/fnins.2020.00098","volume":"14","author":"M Han","year":"2020","unstructured":"Han M, Liu Z, Xu Y, Liu X, Wang D, Li F, et al. Abnormality of m6A mRNA methylation is involved in alzheimer\u2019s disease. Front Neurosci. 2020;14:98.","journal-title":"Front Neurosci"},{"key":"7871_CR116","doi-asserted-by":"crossref","unstructured":"Huang H, Camats-Perna J, Medeiros R, Anggono V, Widagdo J. Altered expression of the m6A Methyltransferase METTL3 in Alzheimer\u2019s disease. eNeuro. 2020;7(5).","DOI":"10.1523\/ENEURO.0125-20.2020"},{"issue":"1","key":"7871_CR117","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s13024-021-00484-x","volume":"16","author":"F Zhao","year":"2021","unstructured":"Zhao F, Xu Y, Gao S, Qin L, Austria Q, Siedlak SL, et al. METTL3-dependent RNA m(6)A dysregulation contributes to neurodegeneration in alzheimer\u2019s disease through aberrant cell cycle events. Mol Neurodegeneration. 2021;16(1):70.","journal-title":"Mol Neurodegeneration"},{"key":"7871_CR118","doi-asserted-by":"crossref","unstructured":"Li R, Xu T, Cai G, Li W, Qi Y, Xiao X, et al. Reduced levels of N6-methyladenosine in RNA of peripheral blood mononuclear cells from patients with Alzheimer\u2019s disease. 2023.","DOI":"10.21203\/rs.3.rs-2699617\/v1"},{"issue":"3","key":"7871_CR119","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/jnc.15882","volume":"166","author":"H He","year":"2023","unstructured":"He H, Zhang Q, Liao J, Lei J, Luo M, Huang J, et al. METTL14 is decreased and regulates m(6) A modification of \u03b1-synuclein in parkinson\u2019s disease. J Neurochem. 2023;166(3):609\u201322.","journal-title":"J Neurochem"},{"key":"7871_CR120","doi-asserted-by":"crossref","unstructured":"Chang M, Lv H, Zhang W, Ma C, He X, Zhao S, et al. Region-specific RNA m(6)A methylation represents a new layer of control in the gene regulatory network in the mouse brain. Open Biology. 2017;7(9).","DOI":"10.1098\/rsob.170166"},{"issue":"1","key":"7871_CR121","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13059-018-1435-z","volume":"19","author":"C Ma","year":"2018","unstructured":"Ma C, Chang M, Lv H, Zhang ZW, Zhang W, He X, et al. RNA m(6)A methylation participates in regulation of postnatal development of the mouse cerebellum. Genome Biol. 2018;19(1):68.","journal-title":"Genome Biol"},{"issue":"6","key":"7871_CR122","doi-asserted-by":"publisher","first-page":"e2004880","DOI":"10.1371\/journal.pbio.2004880","volume":"16","author":"CX Wang","year":"2018","unstructured":"Wang CX, Cui GS, Liu X, Xu K, Wang M, Zhang XX, et al. METTL3-mediated m6A modification is required for cerebellar development. PLoS Biol. 2018;16(6):e2004880.","journal-title":"PLoS Biol"},{"issue":"9","key":"7871_CR123","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.jgg.2022.03.001","volume":"49","author":"Y Yang","year":"2022","unstructured":"Yang Y, Huang G, Jiang X, Li X, Sun K, Shi Y, et al. Loss of Wtap results in cerebellar ataxia and degeneration of purkinje cells. J Genet Genomics. 2022;49(9):847\u201358.","journal-title":"J Genet Genomics"},{"key":"7871_CR124","doi-asserted-by":"publisher","first-page":"1456891","DOI":"10.3389\/fimmu.2024.1456891","volume":"15","author":"M Zhang","year":"2024","unstructured":"Zhang M, Gou Z, Qu Y, Su X. The indispensability of methyltransferase-like 3 in the immune system: from maintaining homeostasis to driving function. Front Immunol. 2024;15:1456891.","journal-title":"Front Immunol"},{"issue":"4","key":"7871_CR125","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1007\/s12079-023-00788-1","volume":"17","author":"Z Wang","year":"2023","unstructured":"Wang Z, Tang N. Unpacking the complexity of nuclear IL-33 (nIL-33): a crucial regulator of transcription and signal transduction. J Cell Communication Signal. 2023;17(4):1131\u201343.","journal-title":"J Cell Communication Signal"},{"issue":"4","key":"7871_CR126","doi-asserted-by":"publisher","first-page":"100042","DOI":"10.1016\/j.cellin.2022.100042","volume":"1","author":"XM Yi","year":"2022","unstructured":"Yi XM, Lian H, Li S. Signaling and functions of interleukin-33 in immune regulation and diseases. Cell Insight. 2022;1(4):100042.","journal-title":"Cell Insight"},{"key":"7871_CR127","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.brainres.2011.02.045","volume":"1385","author":"S Yasuoka","year":"2011","unstructured":"Yasuoka S, Kawanokuchi J, Parajuli B, Jin S, Doi Y, Noda M, et al. Production and functions of IL-33 in the central nervous system. Brain Res. 2011;1385:8\u201317.","journal-title":"Brain Res"},{"key":"7871_CR128","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.3389\/fimmu.2018.02596","volume":"9","author":"K Fairlie-Clarke","year":"2018","unstructured":"Fairlie-Clarke K, Barbour M, Wilson C, Hridi SU, Allan D, Jiang HR. Expression and function of IL-33\/ST2 axis in the central nervous system under normal and diseased conditions. Front Immunol. 2018;9:2596.","journal-title":"Front Immunol"},{"key":"7871_CR129","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.neuroscience.2017.11.028","volume":"369","author":"LX Du","year":"2018","unstructured":"Du LX, Wang YQ, Hua GQ, Mi WL. IL-33\/ST2 pathway as a rational therapeutic target for CNS diseases. Neuroscience. 2018;369:222\u201330.","journal-title":"Neuroscience"},{"issue":"19","key":"7871_CR130","doi-asserted-by":"publisher","first-page":"E2705","DOI":"10.1073\/pnas.1604032113","volume":"113","author":"AK Fu","year":"2016","unstructured":"Fu AK, Hung KW, Yuen MY, Zhou X, Mak DS, Chan IC, et al. IL-33 ameliorates alzheimer\u2019s disease-like pathology and cognitive decline. Proc Natl Acad Sci USA. 2016;113(19):E2705\u201313.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"7871_CR131","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.clim.2011.11.007","volume":"142","author":"GP Christophi","year":"2012","unstructured":"Christophi GP, Gruber RC, Panos M, Christophi RL, Jubelt B, Massa PT. Interleukin-33 upregulation in peripheral leukocytes and CNS of multiple sclerosis patients. Clin Immunol (Orlando Fla). 2012;142(3):308\u201319.","journal-title":"Clin Immunol (Orlando Fla)"},{"issue":"1","key":"7871_CR132","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1476-9255-8-22","volume":"8","author":"AM Miller","year":"2011","unstructured":"Miller AM. Role of IL-33 in inflammation and disease. J Inflamm (London England). 2011;8(1):22.","journal-title":"J Inflamm (London England)"},{"key":"7871_CR133","doi-asserted-by":"crossref","unstructured":"McGrath-Morrow SA, Collaco JM, Detrick B, Lederman HM. Serum interleukin-6 levels and pulmonary function in Ataxia-Telangiectasia. J Pediatr. 2016;171:256 \u2013 61.e1.","DOI":"10.1016\/j.jpeds.2016.01.002"},{"key":"7871_CR134","doi-asserted-by":"crossref","unstructured":"Hui CW, Herrup K. Individual cytokines modulate the neurological symptoms of ATM deficiency in a region specific manner. eNeuro. 2015;2(4).","DOI":"10.1523\/ENEURO.0032-15.2015"},{"issue":"10","key":"7871_CR135","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.2174\/011570159X379620250225075810","volume":"23","author":"C Tang","year":"2025","unstructured":"Tang C, Deng Q, Yuan X, Ding Z, Hu J, Peng L, et al. Peripheral inflammation profile of cerebellar ataxia. Curr Neuropharmacol. 2025;23(10):1276\u201386.","journal-title":"Curr Neuropharmacol"},{"issue":"5","key":"7871_CR136","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1002\/mds.29359","volume":"38","author":"Y V\u00e1zquez-Mojena","year":"2023","unstructured":"V\u00e1zquez-Mojena Y, Rodr\u00edguez-C\u00f3rdova Y, Dominguez-Barrios Y, Le\u00f3n-Arcia K, Miranda-Becerra D, Gonzalez-Zaldivar Y, et al. Peripheral inflammation links with the severity of clinical phenotype in spinocerebellar ataxia 2. Mov Disord. 2023;38(5):880\u20135.","journal-title":"Mov Disord"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-07871-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-07871-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-07871-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:30:47Z","timestamp":1781634647000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-07871-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":136,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["7871"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-07871-2","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]},"assertion":[{"value":"8 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by Institute Pasteur Ethics Committee in Tunisia (reference 2022\/4\/I\/LR16IPT\/V2), in accordance with the Declaration of Helsinki Principles. Written informed consent was obtained from the legal tutor of all patients for genetic investigation and publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors confirm their consent for the publication of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"422"}}