{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:00:58Z","timestamp":1788357658563,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/N000358\/1"],"award-info":[{"award-number":["BB\/N000358\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council Canada","doi-asserted-by":"publisher","award":["1916606"],"award-info":[{"award-number":["1916606"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The developmental disorder Burn\u2010McKeown Syndrome (BMKS) is characterised by choanal atresia and specific craniofacial features. BMKS is caused by biallelic variants in the pre\u2010messenger RNA splicing factor\n                    <jats:italic>TXNL4A<\/jats:italic>\n                    . Most patients have a loss\u2010of\u2010function variant in\n                    <jats:italic>trans<\/jats:italic>\n                    with a 34\u2010base pair (bp) deletion (type 1 \u039434) in the promoter region. Here, we identified two patients with BMKS. One individual has a\n                    <jats:italic>TXNL4A<\/jats:italic>\n                    c.93_94delCC, p.His32Argfs\u2009*21 variant combined with a type 1 \u039434 promoter deletion. The other has an intronic\n                    <jats:italic>TXNL4A<\/jats:italic>\n                    splice site variant (c.258\u20103C&gt;G) and a type 1 \u039434 promoter deletion. We show the c.258\u20103C&gt;G variant and a previously reported c.258\u20102A&gt;G variant, cause skipping of the final exon of\n                    <jats:italic>TXNL4A<\/jats:italic>\n                    in a minigene splicing assay. Furthermore, we identify putative transcription factor binding sites within the 56\u2009bp of the\n                    <jats:italic>TXNL4A<\/jats:italic>\n                    promoter affected by the type 1 and type 2 \u039434 and use dual luciferase assays to identify a 22\u2009bp repeated motif essential for\n                    <jats:italic>TXNL4A<\/jats:italic>\n                    expression within this promoter region. We propose that additional variants affecting critical transcription factor binding nucleotides within the 22\u2009bp repeated motif could be relevant to BMKS aetiology. Finally, our data emphasises the need to analyse the non\u2010coding sequence in individuals where a single likely pathogenic coding variant is identified in an autosomal recessive disorder consistent with the clinical presentation.\n                  <\/jats:p>","DOI":"10.1111\/cge.14082","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T05:14:52Z","timestamp":1635484492000},"page":"255-259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Expanding the genotypic spectrum of\n                    <scp>\n                      <i>TXNL4A<\/i>\n                    <\/scp>\n                    variants in\n                    <scp>Burn\u2010McKeown<\/scp>\n                    syndrome"],"prefix":"10.1111","volume":"101","author":[{"given":"Katherine A.","family":"Wood","sequence":"first","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie M.","family":"Ellingford","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw B.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Genomics UK Research Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8890-7544","authenticated-orcid":false,"given":"Sofia","family":"Douzgou","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester UK"},{"name":"Department of Medical Genetics Haukeland University Hospital  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda M.","family":"Beaman","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Hobson","sequence":"additional","affiliation":[{"name":"Yorkshire Regional Genetics Service Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Prescott","sequence":"additional","affiliation":[{"name":"Yorkshire Regional Genetics Service Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-1289","authenticated-orcid":false,"given":"Raymond T.","family":"O'Keefe","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6382-4678","authenticated-orcid":false,"given":"William G.","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"issue":"3","key":"e_1_2_7_2_1","first-page":"137","article-title":"New dysmorphic syndrome with choanal atresia in siblings","volume":"1","author":"Burns J","year":"1992","journal-title":"Clin Dysmorphol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-199904000-00011"},{"issue":"3","key":"e_1_2_7_4_1","first-page":"171","article-title":"Two brothers with Burn\u2010McKeown syndrome","volume":"12","author":"Wieczorek D","year":"2003","journal-title":"Clin Dysmorphol"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.10.014"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12596"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.107"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61554"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000175"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.55406"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16940"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a003707"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.183"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0233582"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0528-2"},{"key":"e_1_2_7_16_1","unstructured":"KnorrLE\u2010HK Abdel\u2010WahabO.Aberrant RNA splicing in cancer. Published online2019:21."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.636620"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14082","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14082","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T07:18:50Z","timestamp":1693207130000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,5]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1111\/cge.14082"],"URL":"https:\/\/doi.org\/10.1111\/cge.14082","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14082\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14082\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14082\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14082\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14082\/v1\/review2","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,5]]},"assertion":[{"value":"2021-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}