{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:12:33Z","timestamp":1791353553596,"version":"4.3.1"},"reference-count":36,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>\n                    GLI2 is a zinc-finger transcription factor involved in the Sonic Hedgehog pathway. Gli2 mutant mice have hypoplastic anterior and absent posterior pituitary glands. We reviewed the literature for patients with hypopituitarism and alterations in\n                    <jats:italic>GLI2<\/jats:italic>\n                    . Twenty-five patients (16 families) had heterozygous truncating mutations, and the phenotype frequently included GH deficiency, a small anterior pituitary lobe and an ectopic\/undescended posterior pituitary lobe on magnetic resonance imaging and postaxial polydactyly. The inheritance pattern was autosomal dominant with incomplete penetrance and variable expressivity. The mutation was frequently inherited from an asymptomatic parent. Eleven patients had heterozygous non-synonymous\n                    <jats:italic>GLI2<\/jats:italic>\n                    variants that were classified as variants of unknown significance, because they were either absent from or had a frequency lower than 0.001 in the databases. In these patients, the posterior pituitary was also ectopic, but none had polydactyly. A third group of variants found in patients with hypopituitarism were considered benign because their frequency was \u22650.001 in the databases.\n                    <jats:italic>GLI2<\/jats:italic>\n                    is a large and polymorphic gene, and sequencing may identify variants whose interpretation may be difficult. Incomplete penetrance implies in the participation of other genetic and\/or environmental factors. An interaction between\n                    <jats:italic>Gli2<\/jats:italic>\n                    mutations and prenatal ethanol exposure has been demonstrated in mice dysmorphology. In conclusion, a relatively high frequency of\n                    <jats:italic>GLI2<\/jats:italic>\n                    mutations and variants were identified in patients with congenital GH deficiency without other brain defects, and most of these patients presented with combined pituitary hormone deficiency and an ectopic posterior pituitary lobe. Future studies may clarify the relative role and frequency of\n                    <jats:italic>GLI2<\/jats:italic>\n                    alterations in the aetiology of hypopituitarism.\n                  <\/jats:p>","DOI":"10.1530\/jme-15-0009","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T22:16:44Z","timestamp":1429136204000},"page":"R141-R150","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":64,"title":["Role of GLI2 in hypopituitarism phenotype"],"prefix":"10.1530","volume":"54","author":[{"given":"Ivo J P","family":"Arnhold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela M","family":"Fran\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciani R","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice B","family":"Mendonca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A L","family":"Jorge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"issue":"11","key":"1_35619685","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.earlhumdev.2009.08.057","volume":"85","author":"Alatzoglou","year":"2009","journal-title":"Early human development","ISSN":"https:\/\/id.crossref.org\/issn\/0378-3782","issn-type":"print"},{"issue":"6","key":"2_47763936","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1136\/jmedgenet-2013-102249","volume":"51","year":"2014","journal-title":"Journal of Medical Genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0022-2593","issn-type":"print"},{"issue":"2","key":"3_36110412","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1210\/jc.2009-1334","volume":"95","year":"2010","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"2","key":"4_6033275","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/477","volume":"19","author":"Dattani","year":"1998","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"11","key":"5_31775028","doi-asserted-by":"publisher","first-page":"4351","DOI":"10.1210\/jc.2008-1189","volume":"93","year":"2008","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"3","key":"6_45194595","doi-asserted-by":"publisher","first-page":"E567","DOI":"10.1210\/jc.2012-3224","volume":"98","year":"2013","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"11","key":"7_37795347","doi-asserted-by":"publisher","first-page":"E384","DOI":"10.1210\/jc.2010-1050","volume":"95","year":"2010","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"key":"8_47763938","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/cen.12044","volume":"78","year":"2013","journal-title":"Clinical endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"key":"9_50565285","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1111\/cen.12637","volume":"82","year":"2015","journal-title":"Clinical endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"issue":"5","key":"10_22063307","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/j.1399-0004.2006.00601.x","volume":"69","author":"Gustavsson","year":"2006","journal-title":"Clinical genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0009-9163","issn-type":"print"},{"issue":"2","key":"11_15458734","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/dbio.1994.1097","volume":"162","author":"Hui","year":"1994","journal-title":"Developmental biology","ISSN":"https:\/\/id.crossref.org\/issn\/0012-1606","issn-type":"print"},{"issue":"8","key":"12_17526630","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1242\/dev.00364","volume":"130","author":"Karlstrom","year":"2003","journal-title":"Development","ISSN":"https:\/\/id.crossref.org\/issn\/0950-1991","issn-type":"print"},{"issue":"7","key":"13_39932301","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1210\/er.2009-0008","volume":"30","year":"2009","journal-title":"Endocrine Reviews","ISSN":"https:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"key":"14_47763940","first-page":"166","volume":"158","year":"2012","journal-title":"American journal of medical genetics. 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