{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:42:11Z","timestamp":1788306131313,"version":"build-2803163510"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"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>Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the <jats:italic>Nibrin<\/jats:italic> (<jats:italic>NBN)<\/jats:italic> gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an \u201cEastern Slavic NBS hot spot.\u201d The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; <jats:italic>p<\/jats:italic>=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (<jats:italic>n<\/jats:italic>=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, <jats:italic>p<\/jats:italic>=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (<jats:italic>n<\/jats:italic>=7) and immunodeficiency (<jats:italic>n<\/jats:italic>=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions.<\/jats:p>","DOI":"10.3389\/fimmu.2020.602482","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T05:36:11Z","timestamp":1610084171000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5"],"prefix":"10.3389","volume":"11","author":[{"given":"Svetlana O.","family":"Sharapova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga E.","family":"Pashchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia V.","family":"Bondarenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana S.","family":"Vakhlyarskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Prokofjeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina S.","family":"Fedorova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihor","family":"Savchak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliya","family":"Mareika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timur T.","family":"Valiev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Popa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A.","family":"Tuzankina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Vlasova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga S.","family":"Sakovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina A.","family":"Polyakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia V.","family":"Rumiantseva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina V.","family":"Naumchik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana A.","family":"Kulyova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana N.","family":"Aleshkevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Golovataya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina V.","family":"Minakovskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail V.","family":"Belevtsev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena A.","family":"Latysheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana V.","family":"Latysheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Beznoshchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayane","family":"Akopyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halyna","family":"Makukh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena","family":"Kozlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dzmitry S.","family":"Varabyou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ballow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Sing","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolan E.","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina V.","family":"Kondratenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larysa V.","family":"Kostyuchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Aleinikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.004","article-title":"Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks","volume":"3","author":"Digweed","year":"2004","journal-title":"DNA Repair"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-72005-0_6","article-title":"Nijmegen breakage syndrome","volume":"601","author":"Kondratenko","year":"2007","journal-title":"Adv Exp Med Biol"},{"key":"B3","article-title":"Nijmegen Breakage Syndrome","author":"Varon","year":"1993"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e0167984","DOI":"10.1371\/journal.pone.0167984","article-title":"The Slavic NBN Founder Mutation: A Role for Reproductive Fitness","volume":"11","author":"Seemanova","year":"2016","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4614-9209-2_161-1","article-title":"Nijmegen Breakage Syndrome (NBS1)","volume-title":"Encyclopedia of Medical Immunology","author":"Sharapova","year":"2019"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.03.024","article-title":"The clinical and biological overlap between Nijmegen breakage syndrome and Fanconi anemia","volume":"113","author":"Gennery","year":"2004","journal-title":"Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/ncb879","article-title":"Interaction of FANCD2 and NBS1 in the DNA damage response","volume":"4","author":"Nakanishi","year":"2002","journal-title":"Nat Cell Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2016.01.007","article-title":"International Berlin-Frankfurt-Munster (I-BFM) ALL host genetic variation working group. Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome","volume":"59","author":"Pastorczak","year":"2016","journal-title":"Eur J Med Genet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00807","article-title":"Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC) Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT)","volume":"8","author":"Deripapa","year":"2017","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0186-9","article-title":"Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options - a Retrospective Analysis","volume":"35","author":"Wolska-Kusnierz","year":"2015","journal-title":"J Clin Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1136\/adc.70.1.66","article-title":"Long term social adjustment after treatment for childhood cancer","volume":"70","author":"Eiser","year":"1994","journal-title":"Arch Dis Child"},{"key":"B12","article-title":"SF-36 Health Survey","volume-title":"The use of psychological testing for treatment planning and outcomes assessment","author":"Ware","year":"1999"},{"key":"B13","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.jaci.2017.02.036","article-title":"Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders","volume":"141","author":"Slack","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.18620\/1866-8836-2015-4-1-2-31-37","article-title":"Should Allogeneic Hematopoietic Stem Cell Transplantation be a Treatment Option for Patients with Nijmegen Breakage Syndrome? Belarusian Experience","volume":"4","author":"Aleinikova","year":"2015","journal-title":"Cell Ther Transplant"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/123548","article-title":"Non-Hodgkin Lymphoma in Children with Primary Immunodeficiencies: Clinical Manifestations, Diagnosis, and Management, Belarusian Experience","volume":"2015","author":"Fedorova","year":"2015","journal-title":"Lymphoma"},{"key":"B16","first-page":"46","article-title":"Clinical immunology of Nijmegen breakage syndrome in Ukraine: diagnostics and follow-up","volume":"34","author":"Kostyuchenko","year":"2009","journal-title":"Cent Eur J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2002.122724","article-title":"Nijmegen breakage syndrome: clinical characteristics and mutation analysis in eight unrelated Russian families","volume":"140","author":"Resnick","year":"2002","journal-title":"J Pediatr"},{"key":"B18","first-page":"97","volume-title":"The population&Economy, Cartography","author":"Pozdnyak","year":"2008"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00900","article-title":"The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries","volume":"11","author":"Sharapova","year":"2020","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00811-9","article-title":"Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCR\u03b1\u03b2\/CD19 Depletion in Nijmegen Breakage Syndrome","author":"Laberko","year":"2020","journal-title":"J Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00557","article-title":"Hematopoietic Stem Cell Transplantation for DNA Double Strand Breakage Repair Disorders","volume":"7","author":"Wolska-Ku\u015bnierz","year":"2020","journal-title":"Front Pediatr"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.22828","article-title":"Effects of inspiratory muscle training on lung volumes, respiratory muscle strength, and quality of life in patients with ataxia telangiectasia","volume":"49","author":"F\u00e9lix","year":"2014","journal-title":"Pediatr Pulmonol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1750-1172-6-23","article-title":"Safety and caregiver satisfaction with gastrostomy in patients with Ataxia Telangiectasia","volume":"6","author":"Lefton-Greif","year":"2011","journal-title":"Orphanet J Rare Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.602482\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T05:36:14Z","timestamp":1610084174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.602482\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":23,"alternative-id":["10.3389\/fimmu.2020.602482"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.602482","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]},"article-number":"602482"}}