{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:17:47Z","timestamp":1792275467858,"version":"4.4.0"},"reference-count":40,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Context:<\/jats:title>\n                    <jats:p>Holoprosencephaly (HPE) is a developmental defect characterized by wide phenotypic variability, ranging from minor midline malformations (eg, single central incisor) to severe deformities. In 10\u201315% of HPE patients, mutations in specific genes have been identified (eg, SHH, TGIF, SIX3). Pituitary stalk interruption syndrome (PSIS) constitutes a distinct abnormality of unknown pathogenesis, whereas isolated pituitary hypoplasia (IPH) has been linked to various developmental genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Three of our patients with PSIS had a single central incisor, a malformation encountered in some HPE cases. Based on this observation, we initiated a search for mutations in HPE-associated genes in 30 patients with PSIS or IPH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Participants:<\/jats:title>\n                    <jats:p>The entire coding region of the TGIF, SHH, and SIX3 genes was sequenced in patients with combined pituitary hormone deficiency associated with either PSIS or IPH and in healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Two novel mutations in the HPE-related genes were detected (ie, c.799 C&amp;gt;T, p.Q267X in the TGIF gene, and c.1279G&amp;gt;A, p.G427R in the SHH gene) in 2 of our patients. The overall incidence of HPE-related gene mutations in our nonsyndromic and nonchromosomal patients was 6.6%. No molecular defect in the SIX3 gene was detected in our cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The data suggest that HPE-related gene mutations are implicated in the etiology of isolated pituitary defects (PSIS or IPH). Alternatively, PSIS or IPH may constitute mild forms of an expanded HPE spectrum.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jc.2012-3982","type":"journal-article","created":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T23:08:50Z","timestamp":1362784130000},"page":"E779-E784","source":"Crossref","is-referenced-by-count":49,"title":["Pituitary Stalk Interruption Syndrome and Isolated Pituitary Hypoplasia May Be Caused by Mutations in Holoprosencephaly-Related Genes"],"prefix":"10.1210","volume":"98","author":[{"given":"Christina","family":"Tatsi","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, Athens University Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Sertedaki","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, Athens University 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Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kanaka-Gantenbein","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, Athens University Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, Athens University Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Dacou-Voutetakis","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, Athens University Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613510435800_B1","first-page":"3450","article-title":"Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of ist pathogenesis","volume":"82","author":"Pinto","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613510435800_B2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1471-2431-9-29","article-title":"Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency","volume":"9","author":"Louvel","year":"2009","journal-title":"BMC Pediatr"},{"key":"2020071613510435800_B3","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1530\/EJE-10-0892","article-title":"Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms","volume":"164","author":"Reynaud","year":"2011","journal-title":"Eur 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