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Heterozygous and biallelic pathogenic variants in <jats:italic>TET3<\/jats:italic> have recently been described in <jats:italic>TET3<\/jats:italic>\u2010related Beck\u2013Fahrner syndrome (<jats:italic>TET3<\/jats:italic>\u2010BEFAHRS), representing an autosomal dominant disorder with variable expressivity. Typical features include intellectual disability and developmental delay. Patients can also present with facial dysmorphism, seizure disorder, ophthalmic findings, and other neurobehavioral features. As the condition has recently been described and few patients have been reported in literature, the full scope of the phenotypic spectrum and approaches to identify them are still emerging. We report an individual meeting the criteria for <jats:italic>TET3<\/jats:italic>\u2010BEFAHRS confirmed through clinical, genetic, and DNA methylation episignature analysis, who uniquely presents with bilateral chorioretinal and unilateral right iris colobomata. This case suggests a broader ophthalmic phenotype to <jats:italic>TET3<\/jats:italic>\u2010BEFAHRS and demonstrates the utility of episignatures for the diagnosis of Mendelian disorders of epigenetic machinery.<\/jats:p>","DOI":"10.1002\/ajmg.a.63864","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T05:45:46Z","timestamp":1735883146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diagnosis of <i>TET3<\/i>\u2010Related Beck\u2013Fahrner Syndrome in an Individual With Chorioretinal and Iris Colobomata Using a <scp>DNA<\/scp> Methylation Signature"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8011-1864","authenticated-orcid":false,"given":"Alice","family":"Man","sequence":"first","affiliation":[{"name":"Michael G. DeGroote School of Medicine McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6280-3739","authenticated-orcid":false,"given":"Matteo","family":"Di Scipio","sequence":"additional","affiliation":[{"name":"Michael G. DeGroote School of Medicine McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley","family":"McConkey","sequence":"additional","affiliation":[{"name":"Verspeeten Clinical Genome Centre London Health Sciences Centre  London Ontario Canada"},{"name":"Department of Pathology and Laboratory Medicine Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Hough","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics McMaster University  Hamilton Ontario Canada"},{"name":"Department of Pediatrics McMaster Children's Hospital  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Radiology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Diehl","sequence":"additional","affiliation":[{"name":"Division of Genome Diagnostics, Department of Paediatric Laboratory Medicine The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-7671","authenticated-orcid":false,"given":"Christian R.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Division of Genome Diagnostics, Department of Paediatric Laboratory Medicine The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6363-0016","authenticated-orcid":false,"given":"Bekim","family":"Sadikovic","sequence":"additional","affiliation":[{"name":"Verspeeten Clinical Genome Centre London Health Sciences Centre  London Ontario Canada"},{"name":"Department of Pathology and Laboratory Medicine Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5846-4439","authenticated-orcid":false,"given":"Resham","family":"Ejaz","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics McMaster University  Hamilton Ontario Canada"},{"name":"Department of Pediatrics McMaster Children's Hospital  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.03.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.12.007"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0690-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-019-0555-y"},{"key":"e_1_2_9_6_1","volume-title":"GeneReviews\u00ae","author":"Fahrner J. 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