{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:12:21Z","timestamp":1791353541930,"version":"4.3.1"},"reference-count":30,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Context: Although recent studies have suggested a positive role of OTX2 in pituitary as well as ocular development and function, detailed pituitary phenotypes in OTX2 mutations and OTX2 target genes for pituitary function other than HESX1 and POU1F1 remain to be determined.<\/jats:p>\n               <jats:p>Objective: We aimed to examine such unresolved issues.<\/jats:p>\n               <jats:p>Subjects: We studied 94 Japanese patients with various ocular or pituitary abnormalities.<\/jats:p>\n               <jats:p>Results: We identified heterozygous p.K74fsX103 in case 1, p.A72fsX86 in case 2, p.G188X in two unrelated cases (3 and 4), and a 2,860,561-bp microdeletion involving OTX2 in case 5. Clinical studies revealed isolated GH deficiency in cases 1 and 5; combined pituitary hormone deficiency in case 3; abnormal pituitary structures in cases 1, 3, and 5; and apparently normal pituitary function in cases 2 and 4, together with ocular anomalies in cases 1\u20135. The wild-type Orthodenticle homeobox 2 (OTX2) protein transactivated the GNRH1 promoter as well as the HESX1, POU1F1, and IRBP (interstitial retinoid-binding protein) promoters, whereas the p.K74fsX103-OTX2 and p.A72fsX86-OTX2 proteins had no transactivation functions and the p.G188X-OTX2 protein had reduced (\u223c50%) transactivation functions for the four promoters, with no dominant-negative effect. cDNA screening identified positive OTX2 expression in the hypothalamus.<\/jats:p>\n               <jats:p>Conclusions: The results imply that OTX2 mutations are associated with variable pituitary phenotype, with no genotype-phenotype correlations, and that OTX2 can transactivate GNRH1 as well as HESX1 and POU1F1.<\/jats:p>","DOI":"10.1210\/jc.2009-1334","type":"journal-article","created":{"date-parts":[[2009,12,5]],"date-time":"2009-12-05T02:47:42Z","timestamp":1259981262000},"page":"756-764","source":"Crossref","is-referenced-by-count":99,"title":["Heterozygous Orthodenticle Homeobox 2 Mutations Are Associated with Variable Pituitary Phenotype"],"prefix":"10.1210","volume":"95","author":[{"given":"Sumito","family":"Dateki","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism (S.D., N.S., M.F., T.O.), National Children\u2019s Medical Center, Tokyo 157-8535, Japan"},{"name":"Department of Pediatrics (S.D., K.M., E.K., H.M.), Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitaro","family":"Kosaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (K.K.), Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosei","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (K.H., H.T.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (K.H., H.T.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Azuma","sequence":"additional","affiliation":[{"name":"National Research Institute for Child Health and Development, and Division of Ophthalmology (N.A.), National Children\u2019s Medical Center, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Yokoya","sequence":"additional","affiliation":[{"name":"Department of Medical Subspecialties (S.Y.), National Children\u2019s Medical Center, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Muroya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (S.D., K.M., E.K., H.M.), Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Adachi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism (K.M., M.A.), Kanagawa Children\u2019s Medical Center, Yokohama 232-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Tajima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (T.T.), Hokkaido University School of Medicine, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuaki","family":"Motomura","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism (K.M., M.A.), Kanagawa 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism (S.D., N.S., M.F., T.O.), National Children\u2019s Medical Center, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism (S.D., N.S., M.F., T.O.), National Children\u2019s Medical Center, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613545419100_R1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1210\/er.2001-0030","article-title":"Molecular basis of combined pituitary hormone deficiencies","volume":"23","author":"Cohen","year":"2002","journal-title":"Endocr Rev"},{"issue":"Suppl 5","key":"2020071613545419100_R2","first-page":"138","article-title":"Hypopituitarism 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