{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:05:16Z","timestamp":1790168716249,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271889"],"award-info":[{"award-number":["82271889"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371173"],"award-info":[{"award-number":["82371173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018625","name":"Science and Technology Innovation Plan Of Shanghai Science and Technology Commission","doi-asserted-by":"publisher","award":["23ZR1409400"],"award-info":[{"award-number":["23ZR1409400"]}],"id":[{"id":"10.13039\/501100018625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018625","name":"Science and Technology Innovation Plan Of Shanghai Science and Technology Commission","doi-asserted-by":"publisher","award":["24ZR1409400"],"award-info":[{"award-number":["24ZR1409400"]}],"id":[{"id":"10.13039\/501100018625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Treacher Collins syndrome (TCS) is a congenital craniofacial disorder characterized by malar and mandibular hypoplasia, downward\u2010slanting palpebral fissures, and conductive hearing loss. Pathogenic variants in\n                      <jats:italic>TCOF1<\/jats:italic>\n                      account for most cases, with POLR1D, POLR1C, and POLR1B also implicated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole\u2010exome sequencing was performed in a two\u2010generation Chinese family with TCS, followed by Sanger sequencing validation. Clinical features were systematically evaluated, and bioinformatic analyses combined with structural modeling were employed to assess the potential pathogenicity of the identified variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this study, a novel heterozygous frameshift variant in\n                      <jats:italic>TCOF1<\/jats:italic>\n                      (NM_001371623.1:c.1601_1602delCC, p.Pro534Leufs*15) was identified in the proband and his affected father. The proband presented classic TCS features including craniofacial skeletal hypoplasia, downward\u2010slanting palpebral fissures, and conductive hearing loss. He also carried a right\u2010sided preauricular fistula, a nonclassical feature of TCS. The same variant was detected in his affected father with a substantially milder phenotype, indicating marked intrafamilial phenotypic variability. Bioinformatic analysis and structural modeling predicted that this variant produces a severely truncated Treacle protein lacking key functional domains, which is predicted to disrupt nucleolar localization and ribosome biogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings expand the variant spectrum of\n                      <jats:italic>TCOF1<\/jats:italic>\n                      , highlight phenotypic heterogeneity in TCS, and reinforce the critical role of molecular diagnosis in distinguishing TCS from phenotypically overlapping craniofacial syndromes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70297","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:56:13Z","timestamp":1789386973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <scp>\n                      <i>TCOF1<\/i>\n                    <\/scp>\n                    Frameshift Variant and Phenotypic Heterogeneity in a Chinese Family With Treacher Collins Syndrome"],"prefix":"10.1002","volume":"14","author":[{"given":"Feiyang","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Facial Plastic and Reconstructive Surgery, Eye &amp; ENT Hospital, ENT Institute Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5685-9832","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Facial Plastic and Reconstructive Surgery, Eye &amp; ENT Hospital, ENT Institute Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Facial Plastic and Reconstructive Surgery, Eye &amp; ENT Hospital, ENT Institute Fudan University  Shanghai China"},{"name":"NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9074-8570","authenticated-orcid":false,"given":"Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Facial Plastic and Reconstructive Surgery, Eye &amp; ENT Hospital, ENT Institute Fudan University  Shanghai China"},{"name":"Institute of Medical Genetics &amp; Genomics Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases Fudan University  Shanghai China"},{"name":"Surgery Laboratory, Institute of Medical Sciences General Hospital of Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"e_1_2_13_2_1","volume-title":"GeneReviews [Internet]","author":"Barbosa M.","year":"2024"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.2"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1320066"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-025-03667-7"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30010"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603730103"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1136-z"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052482"},{"key":"e_1_2_13_10_1","first-page":"6","article-title":"Grading System for the Selection of Patients With Congenital Aural Atresia","volume":"13","author":"Jahrsdoerfer R. 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