{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:46:14Z","timestamp":1761061574257,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RF-2011-02348212"],"award-info":[{"award-number":["RF-2011-02348212"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Opitz G\/BBB syndrome (OS) is a rare genetic developmental condition characterized by congenital defects along the midline of the body. The main clinical signs are represented by hypertelorism, laryngo\u2013tracheo\u2013esophageal defects and hypospadias. The X-linked form of the disease is associated with mutations in the MID1 gene located in Xp22 whereas mutations in the SPECC1L gene in 22q11 have been linked to few cases of the autosomal dominant form of this disorder, as well as to other genetic syndromes. In this study, we have undertaken a mutation screening of the SPECC1L gene in samples of sporadic OS cases in which mutations in the MID1 gene were excluded. The heterozygous missense variants identified are already reported in variant databases raising the issue of their pathogenetic meaning. Recently, it was reported that some clinical manifestations peculiar to OS signs are not observed in patients carrying mutations in the SPECC1L gene, leading to the proposal of the designation of \u2018SPECC1L syndrome\u2019 to refer to this disorder. Our study confirms that patients with diagnosis of OS, mainly characterized by the presence of hypospadias and laryngo\u2013tracheo\u2013esophageal defects, do not carry pathogenic SPECC1L mutations. In addition, SPECC1L syndrome-associated mutations are clustered in two specific domains of the protein, whereas the missense variants detected in our work lies elsewhere and the impact of these variants in the function of this protein is difficult to ascertain with the current knowledge and will require further investigations. Nonetheless, our study provides further insight into the SPECC1L syndrome classification.<\/jats:p>","DOI":"10.3390\/genes13020252","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T01:41:59Z","timestamp":1643420519000},"page":"252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SPECC1L Mutations Are Not Common in Sporadic Cases of Opitz G\/BBB Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Chiara","family":"Migliore","sequence":"first","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Vendramin","sequence":"additional","affiliation":[{"name":"Genomic and Bioinformatic Lab., Cluster in Biomedicine, S.c.r.l., 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1772-0106","authenticated-orcid":false,"given":"Shane","family":"McKee","sequence":"additional","affiliation":[{"name":"Northern Ireland Regional Genetics Service, Belfast City Hospital, Belfast BT9 7AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, University and Hospital of Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Faravelli","sequence":"additional","affiliation":[{"name":"The North East Thames Regional Genetics Service, Great Ormond Street Hospital, London WC1N 3JH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rani","family":"Sachdev","sequence":"additional","affiliation":[{"name":"St George and Sydney Children\u2019s Hospital, Randwick, Sydney, NSW 2031, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Dias","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica, Hospital de Santa Maria, Centro Universit\u00e1rio Hospitalar Lisboa Norte, 1649-028 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Mascaro","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danilo","family":"Licastro","sequence":"additional","affiliation":[{"name":"Area Science Park, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2531-114X","authenticated-orcid":false,"given":"Germana","family":"Meroni","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","first-page":"95","article-title":"The G syndrome of multiple congenital anomalies","volume":"2","author":"Opitz","year":"1969","journal-title":"Birth Defects Orig. 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