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While disruption of several transcription factors has been identified in SOD cohorts, most cases lack a genetic diagnosis, with multifactorial risk factors being thought to play a role. Exome sequencing in a cohort of families with a clinical diagnosis of SOD identified a genetic diagnosis in 3\/6 families, de novo variants in SOX2, SHH, and ARID1A, and explored variants of uncertain significance in the remaining three. The outcome of this study suggests that investigation for a genetic etiology is warranted in individuals with SOD, particularly in the presence of additional syndromic anomalies and when born to older, multigravida mothers. The identification of causative variants in SHH and ARID1A further expands the phenotypic spectra associated with these genes and reveals novel pathways to explore in septo-optic dysplasia.<\/jats:p>","DOI":"10.3390\/genes13071165","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T23:59:22Z","timestamp":1656460762000},"page":"1165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Novel Genetic Diagnoses in Septo-Optic Dysplasia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-6336","authenticated-orcid":false,"given":"Linda M.","family":"Reis","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Children\u2019s Research Institute, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Seese","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children\u2019s Research Institute, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohit","family":"Maheshwari","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald","family":"Basel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children\u2019s Research Institute, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LuAnn","family":"Weik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children\u2019s Research Institute, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"McCarrier","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children\u2019s Research Institute, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"University of Washington Center for Mendelian Genomics","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0531-3586","authenticated-orcid":false,"given":"Elena V.","family":"Semina","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children\u2019s Research Institute, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Departments of Ophthalmology and Cell Biology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.beem.2010.06.008","article-title":"Septo-optic dysplasia and other midline defects: The role of transcription factors: HESX1 and beyond","volume":"25","author":"McCabe","year":"2011","journal-title":"Best Pract. 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