{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T02:25:42Z","timestamp":1778984742734,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione IRCCS Ca\u2032 Granda Ospedale Maggiore Policlinico di Milano"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Moebius syndrome (MBS) is a rare congenital disorder characterized by non-progressive facial palsy and ocular abduction paralysis. Most cases are sporadic, but also rare familial cases with autosomal dominant transmission and incomplete penetrance\/variable expressivity have been described. The genetic etiology of MBS is still unclear: de novo pathogenic variants in REV3L and PLXND1 are reported in only a minority of cases, suggesting the involvement of additional causative genes. With the aim to uncover the molecular causative defect and identify a potential genetic basis of this condition, we performed trio-WES on a cohort of 37 MBS and MBS-like patients. No de novo variants emerged in REV3L and PLXND1. We then proceeded with a cohort analysis to identify possible common causative genes among all patients and a trio-based analysis using an in silico panel of candidate genes. However, identified variants emerging from both approaches were considered unlikely to be causative of MBS, mainly due to the lack of clinical overlap. In conclusion, despite this large cohort, WES failed to identify mutations possibly associated with MBS, further supporting the heterogeneity of this syndrome, and suggesting the need for integrated omics approaches to identify the molecular causes underlying MBS development.<\/jats:p>","DOI":"10.3390\/genes15080971","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T06:11:36Z","timestamp":1721887896000},"page":"971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Impact of Genetics in a Large Cohort of Moebius Patients by Trio Whole Exome Sequencing"],"prefix":"10.3390","volume":"15","author":[{"given":"Giada","family":"Moresco","sequence":"first","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6723-9177","authenticated-orcid":false,"given":"Maria Francesca","family":"Bedeschi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5871-9689","authenticated-orcid":false,"given":"Marco","family":"Venturin","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Villa","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jole","family":"Costanza","sequence":"additional","affiliation":[{"name":"Research Laboratories Coordination Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5675-5347","authenticated-orcid":false,"given":"Alessia","family":"Mauri","sequence":"additional","affiliation":[{"name":"Research Laboratories Coordination Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Santaniello","sequence":"additional","affiliation":[{"name":"Research Laboratories Coordination Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-0048","authenticated-orcid":false,"given":"Odoardo","family":"Picciolini","sequence":"additional","affiliation":[{"name":"Pediatric Physical Medicine & Rehabilitation Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Messina","sequence":"additional","affiliation":[{"name":"Pediatric Physical Medicine & Rehabilitation Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Triulzi","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica Rosa","family":"Miozzo","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Medical Genetics Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7057-5684","authenticated-orcid":false,"given":"Ornella","family":"Rondinone","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-6997","authenticated-orcid":false,"given":"Laura","family":"Fontana","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Medical Genetics Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,23]]},"reference":[{"key":"ref_1","first-page":"91","article-title":"Ueber angeborene doppelseitige Abducens-Facialis-L\u00e4hmung","volume":"35","author":"Mobius","year":"1888","journal-title":"Munch. 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