{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T23:05:40Z","timestamp":1780355140460,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Agnathia-otocephaly complex (AOC) is a rare and usually lethal malformation typically characterized by hypoplasia or the absence of the mandible, ventromedial and caudal displacement of the ears with or without the fusion of the ears, a small oral aperture with or without a tongue hypoplasia. Its incidence is reported as 1 in 70,000 births and its etiology has been attributed to both genetic and teratogenic causes. AOC is characterized by a wide severity clinical spectrum even when occurring within the same family, ranging from a mild mandibular defect to an extreme facial aberration incompatible with life. Most AOC cases are due to a de novo sporadic mutation. Given the genetic heterogeneity, many genes have been reported to be implicated in this disease but to date, the link to only two genes has been confirmed in the development of this complex: the orthodenticle homeobox 2 (OTX2) gene and the paired related homeobox 1 (PRRX1) gene. In this article, we report a case of a fetus with severe AOC, diagnosed in routine ultrasound scan in the first trimester of pregnancy. The genetic analysis showed a novel 10 bp deletion mutation c.766_775delTTGGGTTTTA in the OTX2 gene, which has never been reported before, together with a missense variant c.778T&gt;C in cis conformation.<\/jats:p>","DOI":"10.3390\/genes13122269","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T02:18:06Z","timestamp":1669947486000},"page":"2269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Agnathia-Otocephaly Complex Due to a De Novo Deletion in the OTX2 Gene"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8763-0114","authenticated-orcid":false,"given":"Marco","family":"Fabiani","sequence":"first","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Libotte","sequence":"additional","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0432-1525","authenticated-orcid":false,"given":"Katia","family":"Margiotti","sequence":"additional","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina Khader Issa","family":"Tannous","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, Department of Obstetrics and Gynecology, UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro, 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Sparacino","sequence":"additional","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"D\u2019Aleo","sequence":"additional","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Monaco","sequence":"additional","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Dello Russo","sequence":"additional","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Mesoraca","sequence":"additional","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Giorlandino","sequence":"additional","affiliation":[{"name":"ALTAMEDICA, Human Genetics Laboratory, Viale Liegi 45, 00198 Rome, Italy"},{"name":"ALTAMEDICA, Department of Prenatal Diagnosis, Fetal-Maternal Medical Centre, Altamedica Viale Liegi 45, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ejmg.2010.09.002","article-title":"Current perspectives on the etiology of agnathia-otocephaly","volume":"53","author":"Gekas","year":"2010","journal-title":"Eur. 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