{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:12:24Z","timestamp":1791353544170,"version":"4.3.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,22]],"date-time":"2014-09-22T00:00:00Z","timestamp":1411344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Sao Paulo State Research Council (FAPESP)","award":["10\/11510-1 - 07\/59365-3"],"award-info":[{"award-number":["10\/11510-1 - 07\/59365-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context and Objective<\/jats:title>\n                    <jats:p>\n                      Sonic Hedgehog (\n                      <jats:italic>SHH<\/jats:italic>\n                      ) and\n                      <jats:italic>GLI2<\/jats:italic>\n                      , an obligatory mediator of SHH signal transduction, are holoprosencephaly (HPE)\u2010associated genes essential in pituitary formation.\n                      <jats:italic>GLI2<\/jats:italic>\n                      variants have been found in patients with congenital hypopituitarism without complex midline cerebral defects (MCD). However, data on the occurrence of\n                      <jats:italic>SHH<\/jats:italic>\n                      mutations in these patients are limited. We screened for\n                      <jats:italic>SHH<\/jats:italic>\n                      and\n                      <jats:italic>GLI2<\/jats:italic>\n                      mutations or copy number variations (CNV) in patients with congenital hypopituitarism without MCD or with variable degrees of MCD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>\n                      Detailed data on clinical, laboratory and neuroimaging findings of 115 patients presenting with congenital hypopituitarism without MCD, septo\u2010optic dysplasia or HPE were analysed. The\n                      <jats:italic>SHH<\/jats:italic>\n                      and\n                      <jats:italic>GLI2<\/jats:italic>\n                      genes were directly sequenced, and the presence of gene CNV was analysed by multiplex ligation\u2010dependent probe amplification (MLPA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Anterior pituitary deficiency was found in 74% and 53% of patients with SOD or HPE, respectively. Diabetes insipidus was common in patients with HPE (47%) but infrequent in patients with congenital hypopituitarism or SOD (7% and 8%, respectively). A single heterozygous nonsense\n                      <jats:italic>SHH<\/jats:italic>\n                      mutation (p.Tyr175Ter) was found in a patient presenting with hypopituitarism and alobar HPE. No other SHH mutations or CNV were found. Nine\n                      <jats:italic>GLI2<\/jats:italic>\n                      variations (8 missense and 1 frameshift) including a homozygous and a compound heterozygous variation were found in patients with congenital hypopituitarism or SOD, but not in HPE patients. No\n                      <jats:italic>GLI2<\/jats:italic>\n                      CNV were found.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>SHH<\/jats:italic>\n                      mutations or copy number variations are not a common cause of congenital hypopituitarism in patients without complex midline cerebral defects.\n                      <jats:italic>GLI2<\/jats:italic>\n                      variants are found in some patients with congenital hypopituitarism without complex midline cerebral defects or septo\u2010optic dysplasia. However, functional analyses of these variants are needed to strengthen genotype\u2013phenotype relationship.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.12565","type":"journal-article","created":{"date-parts":[[2014,7,23]],"date-time":"2014-07-23T11:57:50Z","timestamp":1406116670000},"page":"562-569","source":"Crossref","is-referenced-by-count":16,"title":["Sonic Hedgehog mutations are not a common cause of congenital hypopituitarism in the absence of complex midline cerebral defects"],"prefix":"10.1111","volume":"82","author":[{"given":"Sabrina Soares","family":"Paulo","sequence":"first","affiliation":[{"name":"Department of Pediatrics School of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio L.","family":"Fernandes\u2010Rosa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics School of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Turatti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Borchers","family":"Coeli\u2010Lacchini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Carlos E.","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics School of Medicine of Ribeirao Preto University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme 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