{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:08:51Z","timestamp":1790611731872,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:00:00Z","timestamp":1632528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY025718"],"award-info":[{"award-number":["R01EY025718"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>SOX2<\/jats:italic> variants and deletions are a common cause of anophthalmia and microphthalmia (A\/M). This article presents data from a cohort of patients with <jats:italic>SOX2<\/jats:italic> variants, some of whom have been followed for 20+ years. Medical records from patients enrolled in the A\/M Research Registry and carrying <jats:italic>SOX2<\/jats:italic> variants were reviewed. Thirty\u2010seven patients were identified, ranging in age from infant to 30\u2009years old. Eye anomalies were bilateral in 30 patients (81.1%), unilateral in 5 (13.5%), and absent in 2 (5.4%). Intellectual disability was present in all with data available and ranged from mild to profound. Seizures were noted in 18 of 27 (66.6%) patients, usually with abnormal brain MRIs (10\/15, 66.7%). Growth issues were reported in 14 of 21 patients (66.7%) and 14 of 19 (73.7%) had gonadotropin deficiency. Genitourinary anomalies were seen in 15 of 19 (78.9%) male patients and 5 of 15 (33.3%) female patients. Patients with <jats:italic>SOX2<\/jats:italic> nucleotide variants, whole gene deletions or translocations are typically affected with bilateral or unilateral microphthalmia and anophthalmia. Other associated features include intellectual disability, seizures, brain anomalies, growth hormone deficiency, gonadotropin deficiency, and genitourinary anomalies. Recommendations for newly diagnosed patients with <jats:italic>SOX2<\/jats:italic> variants include eye exams, MRI of the brain and orbits, endocrine and neurology examinations. Since the clinical spectrum associated with <jats:italic>SOX2<\/jats:italic> alleles has expanded beyond the originally reported phenotypes, we propose a broader term, <jats:italic>SOX2<\/jats:italic>\u2010associated disorder, for this condition.<\/jats:p>","DOI":"10.1002\/ajmg.a.62518","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T11:42:45Z","timestamp":1632570165000},"page":"187-198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Review of 37 patients with <scp><i>SOX2<\/i><\/scp> pathogenic variants collected by the Anophthalmia\/Microphthalmia Clinical Registry and <scp>DNA<\/scp> research study"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3234-3596","authenticated-orcid":false,"given":"Louise","family":"Amlie\u2010Wolf","sequence":"first","affiliation":[{"name":"Einstein Medical Center Philadelphia  West Philadelphia Pennsylvania USA"},{"name":"Nemours Children's Hospital Delaware  Wilmington DE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Bardakjian","sequence":"additional","affiliation":[{"name":"Einstein Medical Center Philadelphia  West Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics and Children's Research Institute Medical College of Wisconsin, Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina M.","family":"Kopinsky","sequence":"additional","affiliation":[{"name":"Einstein Medical Center Philadelphia  West Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children's Research Institute Medical College of Wisconsin, Children's Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Semina","sequence":"additional","affiliation":[{"name":"Einstein Medical Center Philadelphia  West Philadelphia Pennsylvania USA"},{"name":"Department of Ophthalmology and Visual Sciences, Department of Cell Biology, Neurobiology and Anatomy Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital of University of Pennsylvania  330 South Ninth Street, Philadelphia PA USA"},{"name":"Department of Pediatric Ophthalmology and Ocular Genetics Wills Eye Hospital  840 Walnut Street, Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21606"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2007.117929"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40644"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12275"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31524"},{"key":"e_1_2_11_7_1","volume-title":"Clinical characteristics of intellectual disabilities. 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