{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T21:43:16Z","timestamp":1767994996346,"version":"3.49.0"},"reference-count":44,"publisher":"The Endocrine Society","issue":"10","funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["# 11779\/13-6"],"award-info":[{"award-number":["# 11779\/13-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Ectopic posterior pituitary (EPP), a condition in which the posterior pituitary gland is displaced due to defective neuronal migration, is frequently associated with hypopituitarism. Genetic variants play a role, but many cases remain unexplained.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>A large EPP cohort was studied to explore the importance of genetic variants and how they correlate with clinical findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing was performed on a discovery sample of 27 cases to identify rare variants. The variants that met the criteria for rarity and biological relevance, or that were previously associated with EPP (ROBO1 and HESX1), were then resequenced in the 27 cases plus a replication sample of 51 cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 16 different variants in 12 genes in 15 of the 78 cases (19.2%). Complete anterior pituitary deficiency was twice as common in cases with variants of interest compared to cases without variants (9\/15 [60%] vs 19\/63 [30.1%], respectively; Z test, P\u2005=\u20050.06). Breech presentation was more frequent in the variant positive group (5\/15 vs 1\/63; Z test, P\u2005=\u20050.003). Four cases had variants in ROBO1 and 1 in HESX1, genes previously associated with EPP. The ROBO1 p.S18* variant has not been reported previously; ROBO1 p.Q1227H has not been associated with EPP previously.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>EPP cases with variants of interest identified in this study were more likely to present with severe clinical disease. Several variants were identified in genes not previously associated with EPP. Our findings confirm that EPP is a multigenic disorder. Future studies are needed to identify additional genes.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jendso\/bvac116","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T21:47:14Z","timestamp":1660254434000},"source":"Crossref","is-referenced-by-count":4,"title":["Whole Exome Sequencing in Patients With Ectopic Posterior Pituitary"],"prefix":"10.1210","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-7411","authenticated-orcid":false,"given":"Tatiane S","family":"Silva","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Unit, Irmandade da Santa Casa de Miseric\u00f3rdia de S\u00e3o Paulo and Santa Casa SP School of Medical Sciences , S\u00e3o Paulo , Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7959-9842","authenticated-orcid":false,"given":"Fabio R","family":"Faucz","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) , Bethesda, MD 20892 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6599-6406","authenticated-orcid":false,"given":"Laura C","family":"Hern\u00e1ndez-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) , Bethesda, MD 20892 , USA"},{"name":"Red de Apoyo a la Investigaci\u00f3n, Coordinaci\u00f3n de la Investigaci\u00f3n Cient\u00edfica, Universidad Nacional Aut\u00f3noma de M\u00e9xico e Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n , 15 Vasco de Quiroga, Radiation Oncology building, 2nd floor, Belisario Dom\u00ednguez secci\u00f3n 16. 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