{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T23:03:25Z","timestamp":1773961405097,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,7]],"date-time":"2013-02-07T00:00:00Z","timestamp":1360195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Here, we report two extraordinarily severe cases of Teacher Collins syndrome. Initially, amniotic bands and plical fold disruption were considered, but downslanting eyes made us consider severe Treacher Collins syndrome. A<jats:italic>TCOF1<\/jats:italic>mutation in exon 24 was identified in Patient 1 (c.4355_4356ins14, resulting in p.1456Thrfs*18). Patient 2, who expired on day 4, is so similar to Patient 1 that severe Treacher Collins syndrome may be inferred in this instance. Neither the<jats:italic>TCOF1<\/jats:italic>mutation nor the well\u2010known variability in the expression in affected families with Treacher Collins syndrome (\u223c40% of reported cases) can explain the severity of these cases; otherwise, we would be aware of such cases within families from time to time. We are unaware of any recent sporadic cases (\u223c60% of reported cases) exactly like ours either with a single exception in the case reported by Writzl et al. [<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib27\">2008<\/jats:ext-link>] with a<jats:italic>TCOF1<\/jats:italic>mutation. The case described by Otto in 1841 is spectacular. We propose several hypotheses to be considered in explaining this developmental amplification, including some promoter effect on the gene, some position effect on the gene, a polymorphism elsewhere in the gene, a point mutation elsewhere in the gene, a polymorphism in another gene, or a point mutation in another gene, such as<jats:italic>POLR1C<\/jats:italic>(which maps to 6p21.1) or<jats:italic>POLR1D<\/jats:italic>(which maps to13q12.2). We also review the etiology and pathogenesis of Treacher Collins syndrome, and discuss several other severe cases from the past. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.35397","type":"journal-article","created":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T02:26:43Z","timestamp":1360290403000},"page":"445-452","source":"Crossref","is-referenced-by-count":6,"title":["Two extraordinarily severe cases of Treacher Collins syndrome"],"prefix":"10.1002","volume":"161","author":[{"given":"Mislen","family":"Bauer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilmar","family":"Saldarriaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Anthony","family":"Wolfe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Bruce","family":"Beckwith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime L.","family":"Frias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Michael","family":"Cohen Jr.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,2,7]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1","article-title":"Gross deletions in TCOF1 are the cause of Treacher Collins\u2010Franceschetti syndrome","author":"Bowman M","year":"2012","journal-title":"Eur J Hum Genet"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.25.4.230"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.724"},{"key":"e_1_2_8_5_1","first-page":"96","article-title":"Treacher Collins syndrome: Correlation between clinical and genetic linkage studies","volume":"3","author":"Dixon MJ","year":"1994","journal-title":"Clin Dysmorphol"},{"key":"e_1_2_8_6_1","first-page":"727","article-title":"Sequence analysis, identification of evolutionary conserved motifs and expression analysis of Tcof1 provide futher evidence for a potential function for the gene and its human homologue, TCOF1","volume":"6","author":"Dixon J","year":"1997","journal-title":"Hum Mol Cell"},{"key":"e_1_2_8_7_1","first-page":"1473","article-title":"Increased levels of apoptosis in the in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins","volume":"9","author":"Dixon J","year":"2000","journal-title":"Hum Mol Cell"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603730103"},{"key":"e_1_2_8_9_1","first-page":"515","article-title":"The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature\u2010termination codon","volume":"60","author":"Edwards SJ","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1093\/oso\/9780195118612.003.0019","volume-title":"Syndromes of the head and neck","author":"Gorlin RJ","year":"2001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32816"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960102)61:1<71::AID-AJMG14>3.0.CO;2-T"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30038"},{"key":"e_1_2_8_14_1","first-page":"188","article-title":"Characterization of the nucleolar gene product, treacle, in Treacher Collins syndrome","volume":"11","author":"Isaac C","year":"2001","journal-title":"Mol Biol Cell"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1995.01890050009002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-10-136"},{"key":"e_1_2_8_17_1","unstructured":"OMIM 154500 (Treacher Collins Syndrome 2011); OMIM 613717 (Treacher Collins Syndrome 2 2011); OMIM 248390 (Treacher Collins Syndrome 3 2011)."},{"key":"e_1_2_8_18_1","unstructured":"OMIM 606847 (TCOF1Gene 2011); OMIM 6137715(POLR1DGene 2011); OMIM 610060(POLR1Cgene 2011)."},{"key":"e_1_2_8_19_1","volume-title":"Descriptio Monstrorum Sexcentorum","author":"Otto AW","year":"1841"},{"key":"e_1_2_8_20_1","first-page":"49","article-title":"Another face of the Treacher Collins (TCOF1) gene: Identification of additional exons","volume":"328","author":"So RB","year":"2004","journal-title":"Genes"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.7.493"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20159"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31715"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.221"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33454"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0296-130"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32404"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.35397","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T18:35:14Z","timestamp":1714934114000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.35397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,7]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1002\/ajmg.a.35397"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.35397","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,7]]}}}