{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:26:58Z","timestamp":1790105218835,"version":"4.0.1"},"reference-count":18,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"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":[[2009,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interpretation of the pathogenicity of sequence alterations in disease\u2010associated genes is challenging. This is especially true for novel alterations that lack obvious functional consequences. We report here on a patient with Treacher Collins syndrome (TCS) found to carry a previously reported mutation, c.122C\u2009&gt;\u2009T, which predicts p.A41V, and a novel synonymous mutation, c.3612A\u2009&gt;\u2009C. Pedigree analysis showed that the c.122C\u2009&gt;\u2009T mutation segregated with normal phenotypes in multiple family members while the c.3612A\u2009\u2009&gt;\u2009\u2009C was de novo in the patient. Analysis of <jats:italic>TCOF1<\/jats:italic> RNA in lymphocytes showed a transcript missing exon 22. These results show that TCS in the patient is due to haploinsufficiency of TCOF1 caused by the synonymous de novo c.3612A\u2009&gt;\u2009C mutation. This study highlights the importance of clinical and pedigree evaluation in the interpretation of known and novel sequence alterations. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32834","type":"journal-article","created":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T18:02:07Z","timestamp":1246471327000},"page":"1624-1627","source":"Crossref","is-referenced-by-count":37,"title":["A synonymous mutation in <i>TCOF1<\/i> causes Treacher Collins syndrome due to mis\u2010splicing of a constitutive exon"],"prefix":"10.1002","volume":"149A","author":[{"given":"D.","family":"Macaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.H.","family":"Katsanis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.W.","family":"Hefferon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Audlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.J.","family":"Mendelsohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Roggenbuck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.R.","family":"Cutting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg775"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg616"},{"key":"e_1_2_6_4_1","first-page":"17","article-title":"The gene for Treacher Collins syndrome maps to the long arm of chromosome 5","volume":"49","author":"Dixon MJ","year":"1991","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_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_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.10.1473"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30010"},{"key":"e_1_2_6_8_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_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ortho\/29.4.293"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073774"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1048803"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/ng0296-130","article-title":"Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. 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