{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:47:01Z","timestamp":1777355221229,"version":"3.51.4"},"reference-count":14,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosomal instability disorder characterized by microcephaly, immunodeficiency, radiosensitivity and a very high predisposition to malignancy. The gene responsible for the disease, <jats:italic>NBS1<\/jats:italic>, is located on chromosome 8q21 and encodes a protein called nibrin. After identification of the gene, a truncating 5 bp deletion, 657-661delACAAA, was identified as the disease-causing mutation in patients with the NBS. In this report, we describe two patients with NBS and T-lymphoblastic leukemia\/lymphoma in a Macedonian family. To the best of our knowledge, this is the first family with NBS reported from Macedonia. Both children presented with microcephaly, syndactyly and the development of T cell lymphoblastic lekemia\/lymphoma at the age of 7 and 10 years, respectively. The molecular analysis of <jats:italic>NBS1<\/jats:italic> genes in our patients showed homozygosity for the 657del5 mutation in the <jats:italic>NBS1<\/jats:italic> gene. The parents were heterozygotes for the 657del5 mutation and they had no knowledge of a consanguineous relationship. The first child was treated with the International Berlin-Frankfurt-M\u00fcnster (BFM)-Non Hodgkin lymphoma (NHL) protocol and achieved a complete remission that lasted for 21 months. Subsequently, he developed a medullar relapse with hyperleukocytosis and died due to lethal central nervous system (CNS) complications. The second child was treated according to the International Collaborative Treatment Protocol for Children and Adolescents with Acute Lymphoblastic Leukemia 2009 (AIOP-BFM ALL 2009) protocol. Unfortunately, remission was not achieved.<\/jats:p>","DOI":"10.1515\/bjmg-2016-0012","type":"journal-article","created":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T07:54:48Z","timestamp":1470210888000},"page":"91-94","source":"Crossref","is-referenced-by-count":1,"title":["T-lymphoblastic leukemia\/lymphoma in macedonian patients with Nijmegen breakage syndrome"],"prefix":"10.1515","volume":"19","author":[{"given":"SA","family":"Kocheva","sequence":"first","affiliation":[{"name":"University Children\u2019s Hospital, Medical Faculty, University \u201cSt. Cyril and Methodius,\u201d Skopje, Republic of Macedonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Martinova","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Medical Faculty, University \u201cSt. Cyril and Methodius,\u201d Skopje, Republic of Macedonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z","family":"Antevska-Trajkova","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Medical Faculty, University \u201cSt. Cyril and Methodius,\u201d Skopje, Republic of Macedonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Coneska-Jovanova","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital, Medical Faculty, University \u201cSt. Cyril and Methodius,\u201d Skopje, Republic of Macedonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Eftimov","sequence":"additional","affiliation":[{"name":"Center for Biomolecular Pharmaceutical Analyses, Faculty of Pharmacy, University \u201cSt. Cyril and Methodius,\u201d Skopje, Republic of Macedonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AJ","family":"Dimovski","sequence":"additional","affiliation":[{"name":"Center for Biomolecular Pharmaceutical Analyses, Faculty of Pharmacy, University \u201cSt. Cyril and Methodius,\u201d Skopje, Republic of Macedonia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2016,8,2]]},"reference":[{"key":"2021040620364584679_j_bjmg-2016-0012_ref_001_w2aab3b8c41b1b7b1ab2b2b1Aa","doi-asserted-by":"crossref","unstructured":"International Nijmegen breakage syndrome study group. Nijmegen breakage syndrome. Arch Dis Child. 2000; 82(5): 400-406.","DOI":"10.1136\/adc.82.5.400"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_002_w2aab3b8c41b1b7b1ab2b2b2Aa","unstructured":"Wegner RD, Chrzanowska K, Sperling K, Stumm M. Ataxia-telangiectasia variants (Nijmegen breakage syndrome) In: Ochs HD, Smith CIE, Puck JM, Eds. Immunodeficiency Disorders: A Molecular and Genetic Approach. Oxford, UK: Oxford University Press. 1999: 324-334."},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_003_w2aab3b8c41b1b7b1ab2b2b3Aa","doi-asserted-by":"crossref","unstructured":"Carney Jp, Maser Rs, Olivares H, Davis EM, Le Beau M, Yates JR III, et al. The hMre11\/hRad50 protein complex and Nijmegen breakage syndrome: Linkage of double-strand break repair to the cellular DNA damage response. Cell. 1998; 93(3): 477-486.","DOI":"10.1016\/S0092-8674(00)81175-7"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_004_w2aab3b8c41b1b7b1ab2b2b4Aa","doi-asserted-by":"crossref","unstructured":"Matsuura S, Tauchi H, Nakamura A, Kondo N, Sakamoto S, Endo S, et al. Positional cloning of the gene for Nijmegen breakage syndrome. Nat Genet. 1998; 19(2): 179-181.","DOI":"10.1038\/549"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_005_w2aab3b8c41b1b7b1ab2b2b5Aa","doi-asserted-by":"crossref","unstructured":"Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell. 1998; 93(3): 467-447.","DOI":"10.1016\/S0092-8674(00)81174-5"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_006_w2aab3b8c41b1b7b1ab2b2b6Aa","unstructured":"Saar K, Chrzanowska KH, Stumm M, Jung M, Nurnberg G, Wienker TF, et al. The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1 cM interval on chromosome 8q21. Am J Hum Genet. 1997; 60(3): 605-610."},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_007_w2aab3b8c41b1b7b1ab2b2b7Aa","doi-asserted-by":"crossref","unstructured":"Cerosaletti KM, Lange E, Stringham HM, Weemaes CM, smeets D, S\u00f6lder B, et al. Fine localization of the Nijmegen breakage syndrome gene to 8q21: Evidence for a common founder haplotype. Am J Hum Genet. 1998; 63(1): 125-134.","DOI":"10.1086\/301927"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_008_w2aab3b8c41b1b7b1ab2b2b8Aa","doi-asserted-by":"crossref","unstructured":"D\u2019Amours D, Jackson SR. The Mre11 complex at the crossroads of DNA repair and checkpoint signaling. Nat Rev Mol Cell Biol. 2002; 3(5): 317-327.","DOI":"10.1038\/nrm805"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_009_w2aab3b8c41b1b7b1ab2b2b9Aa","doi-asserted-by":"crossref","unstructured":"Varon R, Seemanowa E, Chrzanowska K, Hnateyko O, Piekutowska-Abramczuk D, Krajewska-Walasek M, et al. Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations. Eur J Hum Genet. 2008; 8(11): 900-902.","DOI":"10.1038\/sj.ejhg.5200554"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_010_w2aab3b8c41b1b7b1ab2b2c10Aa","doi-asserted-by":"crossref","unstructured":"Chrzanowska K, Piekutowska-Abramczuk D, Popowska E, Gladkowska-Dura M, Maldyk J, Syczewska M, et al. Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies. Int J Cancer. 2006; 116(5): 1269-1274.","DOI":"10.1002\/ijc.21439"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_011_w2aab3b8c41b1b7b1ab2b2c11Aa","doi-asserted-by":"crossref","unstructured":"di Masi A, Antoccia A. NBS1 Heterozygosity and cancer risk. Curr Genomics. 2008; 9(4): 275-281.","DOI":"10.2174\/138920208784533610"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_012_w2aab3b8c41b1b7b1ab2b2c12Aa","doi-asserted-by":"crossref","unstructured":"Reiter A, Schrappe M, Parwaresch R, Henze G, M\u00fcller-Weihrich S, Sauter S, et al. Non-Hodgkin\u2019s lymphoma of childhood and adolescence: Results of a treatment stratified for biologic subtypes and stage - A report of Berlin-Frank-furt-M\u00fcnster Group. J Clin Oncol 1995; 13(2): 359-372.","DOI":"10.1200\/JCO.1995.13.2.359"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_013_w2aab3b8c41b1b7b1ab2b2c13Aa","doi-asserted-by":"crossref","unstructured":"Dembowska Baginska B, Perek D, Brozyna A, Wakulinska A, Olczak Kowalczyk D, Gladkowska Dura M, et al. Non Hodgkin lymphoma (NHL) in children with Nijmegen Breakage syndrome (NBS). Pediatr Blood Cancer. 2009; 52(2): 186-190.","DOI":"10.1002\/pbc.21789"},{"key":"2021040620364584679_j_bjmg-2016-0012_ref_014_w2aab3b8c41b1b7b1ab2b2c14Aa","doi-asserted-by":"crossref","unstructured":"Gregorek H, Chrzanovska KH, Michalkiewitz J, Syczewska M, Madalinski K. Heterogeneity of humoral immune abnormalities in children with Nijmegen breakage syndrome: An 8-year follow-up study in a single centre. Clin Exp Immunol. 2002; 130(2): 319-324.","DOI":"10.1046\/j.1365-2249.2002.01971.x"}],"container-title":["Balkan Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/content.sciendo.com\/view\/journals\/bjmg\/19\/1\/article-p91.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.sciendo.com\/article\/10.1515\/bjmg-2016-0012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T01:19:17Z","timestamp":1617758357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.sciendo.com\/article\/10.1515\/bjmg-2016-0012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,1]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,8,2]]},"published-print":{"date-parts":[[2016,6,1]]}},"alternative-id":["10.1515\/bjmg-2016-0012"],"URL":"https:\/\/doi.org\/10.1515\/bjmg-2016-0012","relation":{},"ISSN":["1311-0160"],"issn-type":[{"value":"1311-0160","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,1]]}}}