{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:54:06Z","timestamp":1788998046589,"version":"build-2803163510"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006345","name":"Uniwersytet Mikolaja Kopernika w Toruniu","doi-asserted-by":"publisher","award":["WL131"],"award-info":[{"award-number":["WL131"]}],"id":[{"id":"10.13039\/501100006345","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. However, establishing its molecular diagnosis remains challenging. Chromosomal breakage analysis is the gold standard diagnostic test for this disease. Nevertheless, molecular analysis is always required for the identification of pathogenic alterations in the FA genes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We report here on a family with FA diagnosis in two siblings. Mitomycin C (MMC) test revealed high level of chromosome breaks and radial figures. In both children, array\u2014Comparative Genomic Hybridization (aCGH) showed maternally inherited 16q24.3 deletion, including <jats:italic>FANCA<\/jats:italic> gene, and next generation sequencing (NGS) disclosed paternally inherited novel variants in the <jats:italic>FANCA<\/jats:italic> gene\u2014Asn1113Tyr and Ser890Asn. A third sibling was shown to be a carrier of <jats:italic>FANCA<\/jats:italic> deletion only.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Although genetic testing in FA patients often requires a multi-method approach including chromosome breakage test, aCGH, and NGS, every effort should be made to make it available for whole FA families. This is not only to confirm the clinical diagnosis of FA in affected individuals, but also to enable identification of carriers of FA gene(s) alterations, as it has implications for diagnostic and genetic counselling process.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-022-02424-4","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T11:06:59Z","timestamp":1658228819000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Next-generation sequencing reveals novel variants and large deletion in FANCA gene in Polish family with Fanconi anemia"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2595-6909","authenticated-orcid":false,"given":"Anna","family":"Repczynska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Julga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Skalska-Sadowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena M.","family":"Kacprzak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Bartoszewska-Kubiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Lazarczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Loska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Drozniewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Czerska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Wachowiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Haus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"2424_CR1","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1146\/annurev-cancerbio-030617-050422","volume":"3","author":"J Niraj","year":"2019","unstructured":"Niraj J, F\u00e4rkkil\u00e4 A, D\u2019Andrea AD. The Fanconi anemia pathway in cancer. Annu Rev Cancer Biol. 2019;3:457\u201378.","journal-title":"Annu Rev Cancer Biol"},{"key":"2424_CR2","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s12308-011-0089-5","volume":"4","author":"I Dokal","year":"2011","unstructured":"Dokal I. Inherited bone marrow failure syndromes. J Hematopathol. 2011;4:53\u201360.","journal-title":"J Hematopathol"},{"key":"2424_CR3","first-page":"8.7.1","volume":"85","author":"A Auerbach","year":"2015","unstructured":"Auerbach A. Diagnosis of Fanconi anemia by diepoxybutane analysis. Curr Protoc Hum Genet. 2015;85:8.7.1-8.7.17.","journal-title":"Curr Protoc Hum Genet"},{"key":"2424_CR4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.mrfmmm.2008.11.004","volume":"668","author":"J Winter","year":"2009","unstructured":"Winter J, Joenje H. Genetic and molecular basis of Fanconi anemia. Mutat Res. 2009;668:11\u20139.","journal-title":"Mutat Res"},{"issue":"12","key":"2424_CR5","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.trecan.2017.10.005","volume":"3","author":"M Nepal","year":"2017","unstructured":"Nepal M, Che R, Zhang J, et al. Fanconi anemia signaling and cancer. Trends Cancer. 2017;3(12):840\u201356.","journal-title":"Trends Cancer"},{"issue":"1","key":"2424_CR6","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41572-019-0113-0","volume":"5","author":"AMR Taylor","year":"2019","unstructured":"Taylor AMR, Rothblum-Oviatt C, Ellis NA, et al. Chromosome instability syndromes. Nat Rev Dis Primers. 2019;5(1):64.","journal-title":"Nat Rev Dis Primers"},{"issue":"11","key":"2424_CR7","first-page":"1342","volume":"35","author":"EK Flynn","year":"2014","unstructured":"Flynn EK, Kamat A, Lach FP, et al. Comprehensive analysis of pathogenic deletion variants in Fanconi anemia genes. Hum Mutat. 2014;35(11):1342\u201353.","journal-title":"Hum Mutat"},{"issue":"2","key":"2424_CR8","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/humu.23366","volume":"39","author":"DC Kimble","year":"2018","unstructured":"Kimble DC, Lach FP, Gregg SQ, et al. A comprehensive approach to identification of pathogenic FANCA variants in Fanconi anemia patients and their families. Hum Mut. 2018;39(2):237\u201354.","journal-title":"Hum Mut"},{"issue":"2","key":"2424_CR9","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1182\/blood-2004-01-0083","volume":"104","author":"PS Rosenberg","year":"2004","unstructured":"Rosenberg PS, Huang Y, Alter BP. Individualized risks of first adverse events in patients with Fanconi anemia. Blood. 2004;104(2):350\u20135.","journal-title":"Blood"},{"key":"2424_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/238731","volume":"6","author":"AB Oostra","year":"2012","unstructured":"Oostra AB, Nieuwint AWM, Joenje H, et al. Diagnosis of Fanconi anemia: chromosomal breakage analysis. Anemia. 2012;6:1\u20139.","journal-title":"Anemia"},{"key":"2424_CR11","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/1471-2105-15-182","volume":"15","author":"H Jiang","year":"2014","unstructured":"Jiang H, Lei R, Ding S-W, et al. Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads. BMC Bioinformatics. 2014;15:182.","journal-title":"BMC Bioinformatics"},{"key":"2424_CR12","unstructured":"Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. 2013. Preprint at https:\/\/arxiv.org\/abs\/1303.3997."},{"issue":"9","key":"2424_CR13","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna A, Hanna M, Banks E, et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297\u2013303.","journal-title":"Genome Res"},{"key":"2424_CR14","doi-asserted-by":"crossref","unstructured":"Poplin R, Ruano-Rubio V, DePristo MA, et al. Scaling accurate genetic variant discovery to tens of thousands of samples. 2018. Preprint at https:\/\/www.biorxiv.org\/content\/10.1101\/201178v3.","DOI":"10.1101\/201178"},{"key":"2424_CR15","unstructured":"Garrison E, Marth G. Haplotype-based variant detection from short-read sequencing. 2012. Preprint at http:\/\/arxiv.org\/abs\/1207.3907."},{"issue":"1","key":"2424_CR16","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","volume":"17","author":"W McLaren","year":"2016","unstructured":"McLaren W, Gil L, Hunt SE, et al. The ensembl variant effect predictor. Genome Biol. 2016;17(1):122.","journal-title":"Genome Biol"},{"issue":"3","key":"2424_CR17","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1002\/humu.22932","volume":"37","author":"X Liu","year":"2016","unstructured":"Liu X, Wu C, Li C, Boerwinkle E. dbNSFP v3.0: a one-stop database of functional predictions and annotations for human non-synonymous and splice site SNVs. Hum Mutat. 2016;37(3):235\u201341.","journal-title":"Hum Mutat"},{"issue":"7571","key":"2424_CR18","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"1000Genomes Project Consortium, Auton A, Brooks LD, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68\u201374.","journal-title":"Nature"},{"issue":"5","key":"2424_CR19","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"issue":"22","key":"2424_CR20","doi-asserted-by":"publisher","first-page":"e138","DOI":"10.1182\/blood-2012-12-474585","volume":"121","author":"SC Chandrasekharappa","year":"2013","unstructured":"Chandrasekharappa SC, Lach FP, Kimble DC, et al. Massively parallel sequencing, aCGH, and RNA-Seq technologies provide a comprehensive molecular diagnosis of Fanconi anemia. Blood. 2013;121(22):e138\u201348.","journal-title":"Blood"},{"key":"2424_CR21","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/132856","volume":"2012","author":"N Ameziane","year":"2012","unstructured":"Ameziane N, Sie D, Dentro S, et al. Diagnosis of Fanconi anemia: mutation analysis by next-generation sequencing. Anemia. 2012;2012: 132856.","journal-title":"Anemia"},{"key":"2424_CR22","first-page":"236","volume":"19","author":"GE Nia","year":"2016","unstructured":"Nia GE, Fadaee M, Royer R, et al. Profiling Fanconi anemia gene mutations among Iranian patients. Arch Iran Med. 2016;19:236\u201340.","journal-title":"Arch Iran Med"},{"issue":"1\u20134","key":"2424_CR23","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1159\/000077513","volume":"104","author":"E Call\u00e9n","year":"2004","unstructured":"Call\u00e9n E, Tischkowitz MD, Creus A, et al. Quantitative PCR analysis reveals a high incidence of large intragenic deletions in the FANCA gene in Spanish Fanconi anemia patients. Cytogenet Genome Res. 2004;104(1\u20134):341\u20135.","journal-title":"Cytogenet Genome Res"},{"issue":"3","key":"2424_CR24","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1006\/geno.1997.4675","volume":"41","author":"L Ianzano","year":"1997","unstructured":"Ianzano L, D\u2019Apolito M, Centra M, et al. The genomic organization of the Fanconi Anemia Group A (FAA) gene. Genomics. 1997;41(3):309\u201314.","journal-title":"Genomics"},{"issue":"2","key":"2424_CR25","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.gene.2013.01.016","volume":"518","author":"P Shukla","year":"2013","unstructured":"Shukla P, Rao A, Ghosh K, et al. Identification of novel large intragenic deletion in a family with Fanconi anemia: first molecular report from India and review of literature. Gene. 2013;518(2):470\u20135.","journal-title":"Gene"},{"issue":"4","key":"2424_CR26","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1136\/jmedgenet-2019-106249","volume":"57","author":"M Bogliolo","year":"2020","unstructured":"Bogliolo M, Pujol R, Aza-Carmona M, et al. Optimised molecular genetic diagnosis of Fanconi anaemia by whole exome sequencing and functional studies. J Med Genet. 2020;57(4):258\u201368.","journal-title":"J Med Genet"},{"key":"2424_CR27","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s13052-015-0142-6","volume":"41","author":"PJ Solomon","year":"2015","unstructured":"Solomon PJ, Margaret P, Rajendran R, et al. A case report and literature review of Fanconi anemia (FA) diagnosed by genetic testing. Ital J Pediatr. 2015;41:38.","journal-title":"Ital J Pediatr"},{"issue":"4","key":"2424_CR28","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1159\/000509838","volume":"11","author":"G Toksoy","year":"2020","unstructured":"Toksoy G, Alkaya DU, Bagirova G, Avc\u0131 \u015e, Aghayev A, G\u00fcnes N, et al. Clinical and molecular characterization of Fanconi anemia patients in Turkey. Mol Syndromol. 2020;11(4):183\u201396.","journal-title":"Mol Syndromol"},{"issue":"6","key":"2424_CR29","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1002\/mgg3.160","volume":"3","author":"E Nicchia","year":"2015","unstructured":"Nicchia E, Greco C, De Rocco D, et al. Identification of point mutations and large intragenic deletions in Fanconi anemia using next-generation sequencing technology. Mol Genet Genom Med. 2015;3(6):500\u201312.","journal-title":"Mol Genet Genom Med"},{"key":"2424_CR30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.dnarep.2017.11.001","volume":"61","author":"FZ Francies","year":"2018","unstructured":"Francies FZ, Wainwright R, Poole J, et al. Diagnosis of Fanconi anaemia by ionizing radiation- or mitomycin C-induced micronuclei. DNA Repair (Amst). 2018;61:17\u201324.","journal-title":"DNA Repair (Amst)"},{"issue":"5","key":"2424_CR31","doi-asserted-by":"publisher","first-page":"380","DOI":"10.3343\/alm.2012.32.5.380","volume":"32","author":"HJ Lee","year":"2012","unstructured":"Lee HJ, Park S, Kang HJ, et al. A case report of Fanconi anemia diagnosed by genetic testing followed by prenatal diagnosis. Ann Lab Med. 2012;32(5):380\u20134.","journal-title":"Ann Lab Med"},{"issue":"3","key":"2424_CR32","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/sj.leu.2403280","volume":"18","author":"MD Tischkowitz","year":"2004","unstructured":"Tischkowitz MD, Morgan NV, Grimwade D, et al. Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia. Leukemia. 2004;18(3):420\u20135.","journal-title":"Leukemia"},{"issue":"3","key":"2424_CR33","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3324\/haematol.2017.176131","volume":"103","author":"R Bottega","year":"2018","unstructured":"Bottega R, Nicchia E, Capelli E, et al. Hypomorphic FANCA mutations correlate with mild mitochondrial and clinical phenotype in Fanconi anemia. Haematologica. 2018;103(3):417\u201326.","journal-title":"Haematologica"},{"issue":"5","key":"2424_CR34","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1086\/302627","volume":"65","author":"NV Morgan","year":"1999","unstructured":"Morgan NV, Tipping AJ, Joenje H, et al. High frequency of large intragenic deletions in the Fanconi anemia group A gene. Am J Hum Genet. 1999;65(5):1330\u201341.","journal-title":"Am J Hum Genet"},{"issue":"9","key":"2424_CR35","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/s10038-019-0629-x","volume":"64","author":"D Nie","year":"2019","unstructured":"Nie D, Cao P, Wang F, et al. Analysis of overlapping heterozygous novel submicroscopic CNVs and FANCA-VPS9D1 fusion transcripts in a Fanconi anemia patient. J Hum Genet. 2019;64(9):899\u2013909.","journal-title":"J Hum Genet"},{"issue":"2","key":"2424_CR36","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1002\/humu.20125","volume":"25","author":"O Levran","year":"2005","unstructured":"Levran O, Diotti R, Pujara K, et al. Spectrum of sequence variations in the FANCA gene: an international Fanconi anemia registry (IFAR) study. Hum Mutat. 2005;25(2):142\u20139.","journal-title":"Hum Mutat"},{"issue":"14","key":"2424_CR37","doi-asserted-by":"publisher","first-page":"3759","DOI":"10.1182\/blood-2010-08-299917","volume":"117","author":"M Castella","year":"2011","unstructured":"Castella M, Pujol R, Call\u00e9n E, et al. Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations. Blood. 2011;117(14):3759\u201369.","journal-title":"Blood"},{"issue":"5","key":"2424_CR38","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1111\/j.1600-0609.2004.00240.x","volume":"72","author":"H Tamary","year":"2004","unstructured":"Tamary H, Dgany O, Toledano H, et al. Molecular characterization of three novel Fanconi anemia mutations in Israeli Arabs. Eur J Haematol. 2004;72(5):330\u20135.","journal-title":"Eur J Haematol"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-022-02424-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-022-02424-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-022-02424-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T11:14:38Z","timestamp":1658229278000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-022-02424-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,19]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["2424"],"URL":"https:\/\/doi.org\/10.1186\/s13023-022-02424-4","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,19]]},"assertion":[{"value":"3 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2022","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 conducted in compliance with all ethical research standards. Ethical approval was provided by the Ethics Committee of the Nicolaus Copernicus University. Consent to participate was obtained from all participants of the study and their parents (in case of children under 16 years old).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Signed informed consent was obtained from all participants (and parents of children) of this study for publishing the clinical data, including the photographs.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"282"}}