{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T20:40:03Z","timestamp":1778186403126,"version":"3.51.4"},"reference-count":37,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","award":["Devo-Decode"],"award-info":[{"award-number":["Devo-Decode"]}],"id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["FDT202106013068"],"award-info":[{"award-number":["FDT202106013068"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IAHU-01"],"award-info":[{"award-number":["ANR-10-IAHU-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AXA","award":["T\u00eate et Coeur"],"award-info":[{"award-number":["T\u00eate et Coeur"]}]},{"name":"EUR G.E.N.E.","award":["ANR 17 EURE 0013"],"award-info":[{"award-number":["ANR 17 EURE 0013"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,4,24]]},"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Syngnathia is an ultrarare craniofacial malformation characterised by an inability to open the mouth due to congenital fusion of the upper and lower jaws. The genetic causes of isolated bony syngnathia are unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used whole exome and Sanger sequencing and microsatellite analysis in six patients (from four families) presenting with syngnathia. We used CRISPR\/Cas9 genome editing to generate <jats:italic>vgll2a<\/jats:italic> and <jats:italic>vgll4l<\/jats:italic> germline mutant zebrafish, and performed craniofacial cartilage analysis in homozygous mutants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified homozygous truncating variants in vestigial-like family member 2 (<jats:italic>VGLL2<\/jats:italic>) in all six patients. Two alleles were identified: one in families of Turkish origin and the other in families of Moroccan origin, suggesting a founder effect for each. A shared haplotype was confirmed for the Turkish patients. The <jats:italic>VGLL<\/jats:italic> family of genes encode cofactors of TEAD transcriptional regulators. <jats:italic>Vgll2<\/jats:italic> is regionally expressed in the pharyngeal arches of model vertebrate embryos, and morpholino-based knockdown of <jats:italic>vgll2a<\/jats:italic> in zebrafish has been reported to cause defects in development of pharyngeal arch cartilages. However, we did not observe craniofacial anomalies in <jats:italic>vgll2a<\/jats:italic> or <jats:italic>vgll4l<\/jats:italic> homozygous mutant zebrafish nor in fish with double knockout of <jats:italic>vgll2a<\/jats:italic> and <jats:italic>vgll4l<\/jats:italic>. In <jats:italic>Vgll2<\/jats:italic>\n                     <jats:sup>\u2212\/\u2212<\/jats:sup> mice, which are known to present a skeletal muscle phenotype, we did not identify defects of the craniofacial skeleton.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results suggest that although loss of <jats:italic>VGLL2<\/jats:italic> leads to a striking jaw phenotype in humans, other vertebrates may have the capacity to compensate for its absence during craniofacial development.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-109059","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T13:20:51Z","timestamp":1693833651000},"page":"1084-1091","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Biallelic truncating variants in <i>VGLL2<\/i> cause syngnathia in humans"],"prefix":"10.1136","volume":"60","author":[{"given":"Valeria","family":"Agostini","sequence":"first","affiliation":[{"name":"Laboratory of embryology and genetics of human malformations, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR 1163, Institut Imagine and Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aude","family":"Tessier","sequence":"additional","affiliation":[{"name":"Laboratory of embryology and genetics of human malformations, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR 1163, Institut Imagine and Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabila","family":"Djaziri","sequence":"additional","affiliation":[{"name":"Laboratory of embryology and genetics of human malformations, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMR 1163, Institut Imagine and Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman Hossein","family":"Khonsari","sequence":"additional","affiliation":[{"name":"Service de Chirurgie Maxillofaciale et Chirurgie Plastique, Centre de r\u00e9f\u00e9rence Fentes et Malformations Faciales (MAFACE), H\u00f4pital Necker-Enfants Malades, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Galliani","sequence":"additional","affiliation":[{"name":"Service de Chirurgie Maxillofaciale et Chirurgie Plastique, Centre de r\u00e9f\u00e9rence Fentes et Malformations Faciales (MAFACE), H\u00f4pital Necker-Enfants Malades, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Hidaka","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gokhan","family":"Tuncbilek","sequence":"additional","affiliation":[{"name":"Hacettepe University, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud","family":"Picard","sequence":"additional","affiliation":[{"name":"Service de Chirurgie Maxillofaciale et Chirurgie Plastique, Centre de r\u00e9f\u00e9rence Fentes et Malformations Faciales (MAFACE), H\u00f4pital Necker-Enfants Malades, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ersoy","family":"Konas","sequence":"additional","affiliation":[{"name":"Hacettepe University, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne","family":"Amiel","sequence":"additional","affiliation":[{"name":"Laboratory of embryology and genetics of human malformations, Institut National de la 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