{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:39:01Z","timestamp":1766486341508,"version":"3.41.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"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. Genet."],"abstract":"<jats:p>Ataxia-Telangiectasia (A-T) is a rare, autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, and increased cancer risk. Mutations in the ATM gene, which is essential for DNA damage repair, underlie this condition. This study reports a novel homozygous frameshift mutation (ATM_ex20 c.3062delT, p. Val1021fs) in a Chinese family with two affected siblings. The mutation, located in exon 20, has not been previously documented, expanding the spectrum of ATM mutations. The proband and her older sister presented with classic A-T symptoms, including gait instability and conjunctival telangiectasia. Both siblings presented with immunodeficiency, characterized by low immunoglobulin A (IgA) levels, slightly elevated IgM levels, and elevated alpha-fetoprotein (AFP). Cranial magnetic resonance imaging (MRI) findings revealed cerebellar atrophy and cerebral white matter lesions in both sisters. Interestingly, while both sisters shared the same mutation, their clinical severity differed, highlighting the complexity of genotype-phenotype correlations in A-T. The parents and an unaffected sister were heterozygous carriers, consistent with autosomal recessive inheritance. This study underscores the importance of genetic testing in A-T diagnosis and provides new insights into the genetic diversity of ATM-related diseases. Further research is needed to understand the broader implications of this mutation.<\/jats:p>","DOI":"10.3389\/fgene.2024.1491649","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T11:25:37Z","timestamp":1732879537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel pathogenic ATM mutation with ataxia-telangiectasia in a Chinese family"],"prefix":"10.3389","volume":"15","author":[{"given":"Qiaomin","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enfu","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101653","DOI":"10.1016\/j.arr.2022.101653","article-title":"The hallmarks of aging in Ataxia-Telangiectasia","volume":"79","author":"Aguado","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s12519-017-0011-z","article-title":"Ataxia telangiectasia in Turkey: multisystem involvement of 91 patients","volume":"13","author":"Akturk","year":"2017","journal-title":"World J. Pediatr. WJP"},{"key":"B3","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s10875-021-01147-8","article-title":"Genetic risk variants for class switching recombination defects in ataxia-telangiectasia patients","volume":"42","author":"Amirifar","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1080\/1744666X.2020.1810570","article-title":"Ataxia-telangiectasia: epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management","volume":"16","author":"Amirifar","year":"2020","journal-title":"Expert Rev. Clin. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1111\/pai.13461","article-title":"The spectrum of ATM gene mutations in Iranian patients with ataxia-telangiectasia","volume":"32","author":"Amirifar","year":"2021","journal-title":"Pediatr. Allergy Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/pai.13020","article-title":"Ataxia-telangiectasia: a review of clinical features and molecular pathology","volume":"30","author":"Amirifar","year":"2019","journal-title":"Pediatr. Allergy Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1056\/NEJMra1006610","article-title":"The autosomal recessive cerebellar ataxias","volume":"366","author":"Anheim","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3441","DOI":"10.3892\/mmr.2019.9992","article-title":"Clinical diagnosis and genetic counseling of atypical ataxia-telangiectasia in a Chinese family","volume":"19","author":"Cao","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.3892\/mmr.2019.10402","article-title":"Novel homozygous ataxia-telangiectasia (A-T) mutated gene mutation identified in a Chinese pedigree with A-T","volume":"20","author":"Chen","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B10","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1136\/adc.2006.094268","article-title":"Survival probability in ataxia telangiectasia","volume":"91","author":"Crawford","year":"2006","journal-title":"Arch. Dis. Child."},{"key":"B11","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s13052-023-01509-5","article-title":"A child with polyarthritis and chronic lung disease: a case report of ataxia-telangiectasia","volume":"49","author":"De Nardi","year":"2023","journal-title":"Ital. J. Pediatr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1136\/archdischild-2016-310477","article-title":"Ataxia telangiectasia: presentation and diagnostic delay","volume":"102","author":"Devaney","year":"2017","journal-title":"Arch. Dis. Child."},{"key":"B13","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1097\/NRL.0b013e31815fa5a7","article-title":"Brain MRI abnormalities in ataxia-telangiectasia","volume":"14","author":"Habek","year":"2008","journal-title":"Neurologist"},{"key":"B14","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1183\/16000617.0017-2016","article-title":"Why we should care about ultra-rare disease","volume":"25","author":"Harari","year":"2016","journal-title":"Eur. Respir. Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1212\/01.wnl.0000224878.22821.23","article-title":"Distal spinal muscular atrophy as a major feature in adult-onset ataxia telangiectasia","volume":"67","author":"Hiel","year":"2006","journal-title":"Neurology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1007\/s12017-013-8240-3","article-title":"Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients","volume":"15","author":"Huang","year":"2013","journal-title":"Neuromolecular Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/ejhg.2011.196","article-title":"Underexpression and abnormal localization of ATM products in ataxia telangiectasia patients bearing ATM missense mutations","volume":"20","author":"Jacquemin","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"85","DOI":"10.15586\/aei.v52i1.961","article-title":"Neurological involvement in patients with primary immunodeficiency","volume":"52","author":"Kose","year":"2024","journal-title":"Allergol. Immunopathol. Madr."},{"key":"B19","doi-asserted-by":"publisher","first-page":"380","DOI":"10.11477\/mf.1416201280","article-title":"Ataxia telangiectasia","volume":"71","author":"Kumada","year":"2019","journal-title":"Brain Nerve"},{"key":"B20","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1007\/s00415-012-6738-5","article-title":"Novel mutation in the ATM gene in a Malian family with ataxia telangiectasia","volume":"260","author":"Landour\u00e9","year":"2013","journal-title":"J. Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"103269","DOI":"10.1016\/j.redox.2024.103269","article-title":"Oxidative stress and the multifaceted roles of ATM in maintaining cellular redox homeostasis","volume":"75","author":"Lee","year":"2024","journal-title":"Redox Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.neulet.2015.11.036","article-title":"Novel ATM mutations with ataxia-telangiectasia","volume":"611","author":"Liu","year":"2016","journal-title":"Neurosci. Lett."},{"key":"B23","doi-asserted-by":"publisher","first-page":"975696","DOI":"10.3389\/fped.2023.975696","article-title":"Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literature review","volume":"11","author":"Liu","year":"2023","journal-title":"Front. Pediatr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"15284","DOI":"10.1038\/s41598-017-15127-9","article-title":"Comparing ataxias with oculomotor apraxia: a multimodal study of AOA1, AOA2 and AT focusing on video-oculography and alpha-fetoprotein","volume":"7","author":"Mariani","year":"2017","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"7479","DOI":"10.1038\/s41598-020-64514-2","article-title":"DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype","volume":"10","author":"McGrath-Morrow","year":"2020","journal-title":"Sci. Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.jaci.2011.03.052","article-title":"Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype","volume":"128","author":"Micol","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"497","DOI":"10.4103\/1673-5374.350194","article-title":"Ataxia-telangiectasia mutated plays an important role in cerebellar integrity and functionality","volume":"18","author":"Mitiagin","year":"2023","journal-title":"Neural Regen. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.jpeds.2003.12.046","article-title":"Immunodeficiency and infections in ataxia-telangiectasia","volume":"144","author":"Nowak-Wegrzyn","year":"2004","journal-title":"J. Pediatr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1007\/s12026-024-09494-5","article-title":"Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study","volume":"72","author":"Pereira","year":"2024","journal-title":"Immunol. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/mds.28313","article-title":"Assessment of ataxia rating scales and cerebellar functional tests: critique and recommendations","volume":"36","author":"Perez-Lloret","year":"2021","journal-title":"Mov. Disord."},{"key":"B31","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/s1071-9091(03)00026-3","article-title":"Ataxia-telangiectasia: diagnosis and treatment","volume":"10","author":"Perlman","year":"2003","journal-title":"Semin. Pediatr. Neurol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e0264177","DOI":"10.1371\/journal.pone.0264177","article-title":"The natural history of ataxia-telangiectasia (A-T): a systematic review","volume":"17","author":"Petley","year":"2022","journal-title":"PLoS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s13023-015-0373-z","article-title":"Body composition, muscle strength and hormonal status in patients with ataxia telangiectasia: a cohort study","volume":"10","author":"Pommerening","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1002\/mds.28307","article-title":"Autosomal recessive cerebellar ataxias with elevated alpha-fetoprotein: uncommon diseases, common biomarker","volume":"35","author":"Renaud","year":"2020","journal-title":"Mov. Disord."},{"key":"B35","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s13023-016-0543-7","article-title":"Ataxia telangiectasia: a review","volume":"11","author":"Rothblum-Oviatt","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s12311-014-0557-4","article-title":"Radiological imaging in ataxia telangiectasia: a review","volume":"13","author":"Sahama","year":"2014","journal-title":"Cerebellum"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1212\/01.wnl.0000219042.60538.92","article-title":"Scale for the assessment and rating of ataxia: development of a new clinical scale","volume":"66","author":"Schmitz-H\u00fcbsch","year":"2006","journal-title":"Neurology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1002\/ana.25394","article-title":"Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia","volume":"85","author":"Schon","year":"2019","journal-title":"Ann. Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1228810","DOI":"10.3389\/fneur.2023.1228810","article-title":"Ataxia-telangiectasia in China: a case report of a novel ATM variant and literature review","volume":"14","author":"Shao","year":"2023","journal-title":"Front. Neurol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1159\/000472285","article-title":"Ataxia-telangiectasia: closer to unraveling the mystery","volume":"3","author":"Shiloh","year":"1995","journal-title":"Eur. J. Hum. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1200\/JCO.2014.56.5101","article-title":"Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies","volume":"33","author":"Suarez","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1016\/j.jaci.2023.12.029","article-title":"Causative mechanisms and clinical impact of immunoglobulin deficiencies in ataxia telangiectasia","volume":"153","author":"Takada","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/cge.12453","article-title":"Ataxia telangiectasia: more variation at clinical and cellular levels","volume":"87","author":"Taylor","year":"2015","journal-title":"Clin. Genet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jns.2015.05.022","article-title":"Ataxia-telangiectasia - a historical review and a proposal for a new designation: ATM syndrome","volume":"355","author":"Teive","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1212\/WNL.0b013e3181af33bd","article-title":"Clinical spectrum of ataxia-telangiectasia in adulthood","volume":"73","author":"Verhagen","year":"2009","journal-title":"Neurology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1002\/humu.22016","article-title":"Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study","volume":"33","author":"Verhagen","year":"","journal-title":"Hum. Mutat."},{"key":"B47","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1111\/j.1440-1789.2011.01263.x","article-title":"Neuropathology in classical and variant ataxia-telangiectasia","volume":"32","author":"Verhagen","year":"","journal-title":"Neuropathology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1055\/s-2007-985899","article-title":"Neuromuscular abnormalities in ataxia telangiectasia: a clinical, electrophysiological and muscle ultrasound study","volume":"38","author":"Verhagen","year":"2007","journal-title":"Neuropediatrics"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1491649\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T11:25:40Z","timestamp":1732879540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1491649\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,28]]},"references-count":48,"alternative-id":["10.3389\/fgene.2024.1491649"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2024.1491649","relation":{},"ISSN":["1664-8021"],"issn-type":[{"type":"electronic","value":"1664-8021"}],"subject":[],"published":{"date-parts":[[2024,11,28]]},"article-number":"1491649"}}