{ "abstract": "Background\n\nAtaxia telangiectasia (AT) is a life-threatening multisystem disorder characterized mainly by neurologic manifestations, infections, and malignancy. We aimed to present a comprehensive analysis of demographic, clinical, immunologic, and genetic features and outcomes of patients with AT in Iran.Methods\n\nWe conducted a retrospective cohort study of 305 registered patients with AT enrolled through a national referral network (2002-2025). Diagnosis was established according to the European Society for Immunodeficiencies criteria.Results\n\nMean age at diagnosis and mean age at onset were 72.0 (±46.0) and 25.2 (±35.57) months, respectively. A substantial proportion of patients presented with non-neurological manifestations as their first clinical feature (43.9%). Among non-neurological manifestations, pneumonia was the second most common initial manifestation (13%) and the most frequent infectious complication (30.2%). Variants classified as severe under the predicted loss-of-function (PVS1) criteria were identified in 104 patients, representing 83.8% of those who underwent genetic evaluation. Immunoglobulin abnormalities were detected in 84.7% of patients. A notable proportion of patients showed class switching recombination defects (45.6%), which were associated with a higher burden of clinical morbidity. Median age at death was 12.8 years (95% CI, 11.0-15.0), and the estimated overall survival rates at 5 and 10 years were 81.6% and 60.2%, respectively. Malignancy (28.9%) and respiratory tract infections (20.0%) were the most common causes of death, respectively.Conclusion\n\nThis large national cohort provides a comprehensive characterization of the clinical, immunologic, and genetic landscape of AT and its determinants of outcome, thereby improving diagnostic recognition, risk stratification, and patient management.", "abstract_shown": true, "affiliations": [ "Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.", "Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran.", "Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.", "Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.", "Department of Allergy and Clinical Immunology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.", "Department of Biology (Molecular and Cellular Biology), Islamic Azad University of Mashhad, Mashhad, Iran.", "Department of Immunology and Allergy, Tabriz University of Medical Sciences, Tabriz, Iran.", "Pediatric Respiratory and Sleep Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.", "Department of Pediatrics, School of Medicine, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.", "Department of Pediatrics, Abuzar Children's Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.", "Department of Immunology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.", "Clinical Research Development Unit of Akbar Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.", "Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.", "Children Growth Disorder Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.", "Department of Allergy and Clinical Immunology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.", "Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.", "Immunodeficiecy Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.", "Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.", "Department of Rheumatology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.", "Department of Immunology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran.", "Department of Pediatrics, 17th Shahrivar Children's Hospital, Guilan University of Medical Sciences, Rasht, Iran.", "Immunology and Allergy Department, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.", "Pediatrics Infectious Diseases, Rheumatology and Immunology Unit, Institute of Biomedicine of Seville, University Hospital Vírgen del Rocío/CSIC/University of Seville, Seville, Spain.", "Department of Pharmacology, Pediatrics and Radiology, University of Seville, Seville, Spain.", "Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.", "Pediatric Immunodeficiency, Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.", "Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.", "Paediatric Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, UK.", "Clinic for Pediatric Immunology and Rheumatology, Center for Pediatrics and Adolescent Medicine, University Hospital Bonn, Bonn, Germany." ], "article_type": "research article", "arxiv": null, "author_total": 33, "authors": [ { "affs": [ 0, 1 ], "name": "Saba Fekrvand", "orcid": "0000-0001-7091-9651" }, { "affs": [ 0 ], "name": "Ayda Firouzabadi", "orcid": "0000-0002-8953-840X" }, { "affs": [ 0 ], "name": "Pouya Vakilipour", "orcid": "0000-0003-2244-043X" }, { "affs": [ 0, 1 ], "name": "Dorsa Safari", "orcid": "0000-0002-5849-2808" }, { "affs": [ 0, 1 ], "name": "Samaneh Delavari" }, { "affs": [ 0 ], "name": "Ali Zarezadeh Mehrabadi", "orcid": "0000-0003-0151-6773" }, { "affs": [ 2 ], "name": "Zahra Chavoshzadeh" }, { "affs": [ 3, 4 ], "name": "Hossein Esmaeilzadeh", "orcid": "0000-0003-0288-8181" }, { "affs": [ 2 ], "name": "Samin Sharafian" }, { "affs": [ 5 ], "name": "Farahnaz DorriMoghaddam" }, { "affs": [ 6 ], "name": "Mahnaz Sadeghi-Shabestari" }, { "affs": [ 7 ], "name": "Fatemeh Tarighat Monfared", "orcid": "0000-0002-4532-9462" }, { "affs": [ 8 ], "name": "Ehsan Khoshnezhad Afkham" }, { "affs": [ 3 ], "name": "Soheila Aleyasin" }, { "affs": [ 9 ], "name": "Farhad Abolnezhadian" }, { "affs": [ 10 ], "name": "Reza Salyanchi", "orcid": "0000-0002-7180-1740" }, { "affs": [ 11 ], "name": "Hamid Ahanchian", "orcid": "0000-0003-3532-7428" }, { "affs": [ 12 ], "name": "Arash Kalantari", "orcid": "0000-0002-9967-8422" }, { "affs": [ 13, 14 ], "name": "Nasrin Behniafard", "orcid": "0000-0001-5265-5656" }, { "affs": [ 15 ], "name": "Tooba Momen", "orcid": "0009-0003-1716-8248" }, { "affs": [ 16 ], "name": "Roya Sherkat", "orcid": "0000-0002-8574-2091" }, { "affs": [ 17 ], "name": "Marzieh Tavakol", "orcid": "0000-0003-1312-4486" }, { "affs": [ 18 ], "name": "Sahar Barzamini" }, { "affs": [ 19 ], "name": "Alireza Shafiei", "orcid": "0000-0002-1478-7225" }, { "affs": [ 20 ], "name": "Taher Cheraghi", "orcid": "0000-0002-9596-0930" }, { "affs": [ 21 ], "name": "Ahmad Vosughimotlagh" }, { "affs": [ 3 ], "name": "Najmeh Sepahi", "orcid": "0000-0003-4420-3064" }, { "affs": [ 22, 23 ], "name": "Peter Olbrich", "orcid": "0000-0001-9853-7903" }, { "affs": [ 24, 25 ], "name": "Isabelle Meyts", "orcid": "0000-0003-1214-0302" }, { "affs": [ 26, 27 ], "name": "Andrew R Gennery", "orcid": "0000-0002-6218-1324" }, { "affs": [ 0, 1, 28 ], "name": "Hassan Abolhassani", "orcid": "0000-0002-4838-0407" }, { "affs": [ 0, 1 ], "name": "Nima Rezaei", "orcid": "0000-0002-3836-1827" }, { "affs": [ 0, 1 ], "name": "Reza Yazdani", "orcid": "0000-0002-5578-6595" } ], "bibtex": "https://research.draconitic.com/paper/cbm3s6ehdsnxw.bib", "cited_by": 0, "doi": "10.1111/ene.70810", "fulltext_url": "https://europepmc.org/articles/PMC13726478", "id": "cbm3s6ehdsnxw", "issns": [ "1351-5101", "1468-1331" ], "landing_url": "https://europepmc.org/article/MED/42969471", "language": "eng", "licence": "CC-BY-NC", "licence_label": "CC BY-NC", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Article" ], [ "openalex", "2403|Immunodeficiency and Autoimmune Disorders" ] ], "openalex": "W7225103859", "pdf_url": "https://europepmc.org/articles/PMC13726478?pdf=render", "pmcid": "PMC13726478", "pmid": "42969471", "published": "2026-11-01", "publisher": "Wiley", "ris": "https://research.draconitic.com/paper/cbm3s6ehdsnxw.ris", "sources": [ { "first_seen": "2026-11-03T15:20:53Z", "native_id": "MED:42969471", "source": "europepmc", "url": "https://europepmc.org/article/MED/42969471" }, { "first_seen": "2026-11-05T12:22:49Z", "native_id": "PMC13726478", "source": "pmc", "url": "https://doi.org/10.1111/ene.70810" } ], "subjects": [ { "field": "biology", "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders", "subfield": "immunology" } ], "title": "A Large Multicenter Cohort of Ataxia-Telangiectasia: Clinical, Immunologic, Genetic, and Survival Outcomes.", "title_text": "A Large Multicenter Cohort of Ataxia-Telangiectasia: Clinical, Immunologic, Genetic, and Survival Outcomes.", "type": "peer-reviewed", "updated_at": "2026-11-06T12:22:26Z", "url": "https://research.draconitic.com/paper/cbm3s6ehdsnxw", "venue": "European journal of neurology", "versions": [] }