{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:02:37Z","timestamp":1772776957650,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W01761X\/1"],"award-info":[{"award-number":["MR\/W01761X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n CBFB<\/jats:italic>\n encodes the core\u2010binding factor \u03b2 subunit, a small protein which heterodimerises with RUNX1\u20103 and activates transcription of genes important in bone development. Recently, five families with cleidocranial dysplasia (CCD) were identified harbouring presumed loss of function variants in\n CBFB<\/jats:italic>\n . Prompted by a multidisciplinary team review of an affected mother and daughter from the 100\u2009000 Genomes Project with genetically unsolved CCD, we inspected read alignments and identified a deletion\u2013inversion\u2013deletion that removes the first two exons of\n CBFB<\/jats:italic>\n . This cryptic variant comprised interlinked deletions of 1310\u2009bp and 1935\u2009bp and had remained undetected by both array\u2010CGH and the Canvas algorithm. The rearrangement was likely mediated by a palindromic AluSx repeat <\u20091\u2009kb from the transcriptional start site. Due to high GC content and repeats, reduced read depth is observed at one of the breakpoints. Although the clinical presentation of\n CBFB<\/jats:italic>\n \u2010related CCD appears to be very similar to\n RUNX2<\/jats:italic>\n \u2010related CCD, our patients were of normal stature. The mild developmental delay observed in previously reported cases of\n CBFB<\/jats:italic>\n \u2010related CCD was not observed. In conclusion, our data strengthens the evidence linking aberrations of the core\u2010binding factor complex to CCD and extends the mutational spectrum of pathogenic variants.\n <\/jats:p>","DOI":"10.1111\/cge.14709","type":"journal-article","created":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T20:44:06Z","timestamp":1738529046000},"page":"86-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Cryptic\n \n CBFB<\/i>\n <\/scp>\n Deletion\u2013Inversion Expands the Mutational Spectrum of Variants Associated With Cleidocranial Dysplasia"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7334-0602","authenticated-orcid":false,"given":"Alistair T.","family":"Pagnamenta","sequence":"first","affiliation":[{"name":"Oxford BRC, Centre for Human Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3395-8453","authenticated-orcid":false,"given":"Mona","family":"Hashim","sequence":"additional","affiliation":[{"name":"Oxford BRC, Centre for Human Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University Hospitals Bristol NHS Foundation Trust Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth","family":"Lawton","sequence":"additional","affiliation":[{"name":"Oxford BRC, Centre for Human Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8991-5036","authenticated-orcid":false,"given":"Amaka C.","family":"Offiah","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine The University of Sheffield Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3602-5704","authenticated-orcid":false,"given":"Jenny C.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Oxford BRC, Centre for Human Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5575-0357","authenticated-orcid":false,"given":"Sarah F.","family":"Smithson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University Hospitals Bristol NHS Foundation Trust Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35327"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30927"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2016.12.007"},{"key":"e_1_2_10_5_1","volume-title":"GeneReviews((R))","author":"Machol K.","year":"2006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1050"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1741\u20104520.2004.00043.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31479"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg\u20102022\u2010108739"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035790"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg\u20102022\u2010108753"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.10.15.21265069"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_14_1","article-title":"A Palindrome\u2010Like Structure on 16p13.3 Is Associated With the Formation of Complex Structural Variations and SRRM2 Haploinsufficiency","author":"Pagnamenta A. T.","year":"2023","journal-title":"Human Mutation 2023"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22569"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010022\u201001018\u2010z"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:27:39Z","timestamp":1762928859000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,2]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1111\/cge.14709"],"URL":"https:\/\/doi.org\/10.1111\/cge.14709","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14709\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14709\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,2]]},"assertion":[{"value":"2025-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}