{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:10:29Z","timestamp":1787656229724,"version":"build-2736575974"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The prevalence of congenital hypopituitarism (CH) attributable to known transcription factor mutations appears to be rare and other causative genes for CH remain to be identified. Due to the sporadic occurrence of CH,\n                      <jats:italic>de novo<\/jats:italic>\n                      chromosomal rearrangements could be one of the molecular mechanisms participating in its etiology, especially in syndromic cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify the role of copy number variations (CNVs) in the etiology of CH and to identify novel genes implicated in CH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects and methods<\/jats:title>\n                    <jats:p>\n                      We enrolled 88 (syndromic: 30; non-syndromic: 58) Japanese CH patients. We performed an array comparative genomic hybridization screening in the 30 syndromic CH patients. For all the 88 patients, we analyzed\n                      <jats:italic>PAX6<\/jats:italic>\n                      by PCR-based sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified one heterozygous 310-kb deletion of the\n                      <jats:italic>PAX6<\/jats:italic>\n                      enhancer region in one patient showing isolated GH deficiency (IGHD), cleft palate, and optic disc cupping. We also identified one heterozygous 6.5-Mb deletion encompassing\n                      <jats:italic>OTX2<\/jats:italic>\n                      in a patient with bilateral anophthalmia and multiple pituitary hormone deficiency. We identified a novel\n                      <jats:italic>PAX6<\/jats:italic>\n                      mutation, namely p.N116S in one non-syndromic CH patient showing IGHD. The p.N116S\n                      <jats:italic>PAX6<\/jats:italic>\n                      was associated with an impairment of the transactivation capacities of the PAX6-binding elements.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study showed that heterozygous\n                      <jats:italic>PAX6<\/jats:italic>\n                      mutations are associated with CH patients.\n                      <jats:italic>PAX6<\/jats:italic>\n                      mutations may be associated with diverse clinical features ranging from severely impaired ocular and pituitary development to apparently normal phenotype. Overall, this study identified causative CNVs with a possible role in the etiology of CH in &lt;10% of syndromic CH patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-14-0255","type":"journal-article","created":{"date-parts":[[2014,10,24]],"date-time":"2014-10-24T02:34:08Z","timestamp":1414118048000},"page":"37-45","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":15,"title":["Heterozygous defects in PAX6 gene and congenital hypopituitarism"],"prefix":"10.1093","volume":"172","author":[{"given":"Masaki","family":"Takagi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Nagasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuma","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Amano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Asakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Muroya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonobu","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"10","key":"1_35859101","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/j.tem.2009.06.005","volume":"20","author":"Romero","year":"2009","journal-title":"Trends in endocrinology and metabolism: TEM","ISSN":"https:\/\/id.crossref.org\/issn\/1043-2760","issn-type":"print"},{"issue":"7","key":"2_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":"3_44952949","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.beem.2010.10.014","volume":"25","year":"2011","journal-title":"BEST PRACTICE RESEARCH CLINICAL ENDOCRINOLOGY METABOLISM"},{"issue":"9","key":"4_43813421","doi-asserted-by":"crossref","first-page":"e46008","DOI":"10.1371\/journal.pone.0046008","volume":"7","author":"Takagi","year":"2012","ISSN":"https:\/\/id.crossref.org\/issn\/1932-6203","issn-type":"print"},{"issue":"9","key":"5_22200065","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.1210\/jc.2005-2173","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"key":"6_49234859","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/ajmg.a.33763","volume":"155","year":"2011","journal-title":"American journal of medical genetics. 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