{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:40:15Z","timestamp":1791121215875,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p>Orthodenticle homolog 2 (OTX2) is a homeobox family transcription factor required for brain and eye formation. Various genetic alterations in<jats:italic>OTX2<\/jats:italic>have been described, mostly in patients with severe ocular malformations. In order to expand the knowledge of the spectrum of<jats:italic>OTX2<\/jats:italic>mutation, we performed<jats:italic>OTX2<\/jats:italic>mutation screening in 92 patients with combined pituitary hormone deficiency (CPHD). We directly sequenced the coding regions and exon\u2013intron boundaries of<jats:italic>OTX2<\/jats:italic>in 92 CPHD patients from the Dutch HYPOPIT study in whom mutations in the classical CPHD genes<jats:italic>PROP1<\/jats:italic>,<jats:italic>POU1F1<\/jats:italic>,<jats:italic>HESX1<\/jats:italic>,<jats:italic>LHX3<\/jats:italic>, and<jats:italic>LHX4<\/jats:italic>had been ruled out. Among 92 CPHD patients, we identified a novel heterozygous missense mutation c.401C&gt;G (p.Pro134Arg) in a patient with CPHD, pituitary malformation, and an underdeveloped left optic nerve. Binding of both the wild-type and mutant OTX2 proteins to bicoid binding sites was equivalent; however, the mutant<jats:italic>OTX2<\/jats:italic>exhibited decreased transactivation. We describe a novel missense heterozygous<jats:italic>OTX2<\/jats:italic>mutation that acts as a dominant negative inhibitor of target gene expression in a patient with CPHD, pituitary malformation, and optic nerve hypoplasia. We provide an overview of all<jats:italic>OTX2<\/jats:italic>mutations described till date, which show that<jats:italic>OTX2<\/jats:italic>is a promising candidate gene for genetic screening of patients with CPHD or isolated GH deficiency (IGHD). As the majority of the<jats:italic>OTX2<\/jats:italic>mutations found in patients with CPHD, IGHD, or short stature have been found in exon 5, we recommend starting mutational screening in those patients in exon 5 of the gene.<\/jats:p>","DOI":"10.1530\/eje-12-0333","type":"journal-article","created":{"date-parts":[[2012,6,20]],"date-time":"2012-06-20T04:17:18Z","timestamp":1340165838000},"page":"441-452","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":40,"title":["A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve"],"prefix":"10.1093","volume":"167","author":[{"given":"Darya","family":"Gorbenko Del Blanco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Diaczok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C G","family":"de Graaff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Radovick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita C S","family":"Hokken-Koelega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"10","key":"1_16030137","first-page":"3279","volume":"121","author":"Acampora","year":"1995","journal-title":"Development","ISSN":"https:\/\/id.crossref.org\/issn\/0950-1991","issn-type":"print"},{"issue":"21","key":"2_16078588","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1101\/gad.9.21.2646","volume":"9","author":"Matsuo","year":"1995","journal-title":"Genes &amp; 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