{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T19:39:37Z","timestamp":1769110777098,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:00:00Z","timestamp":1363046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>2<\/jats:italic> is a downstream transcription factor in Sonic Hedgehog signalling, acting early in ventral forebrain and pituitary development. Heterozygous nonsense <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>2<\/jats:italic> mutations have been reported in patients with isolated or combined pituitary hormone deficiency (<jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content>), with or without holoprosencephaly. The aim of this study was to screen for <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>2<\/jats:italic> mutations in a large cohort of patients with congenital <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Patients<\/jats:title><jats:p>The <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>2<\/jats:italic> coding region of 41 patients with severe isolated <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> deficiency (<jats:styled-content style=\"fixed-case\">IGHD<\/jats:styled-content>) and 136 patients with <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content> was amplified by <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> using intronic primers and sequenced. The frequency of <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>2<\/jats:italic> variants was verified in up to 155 <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>razilian controls and in the 1000 <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>enomes database. The consequences of allelic variants were analysed by the Polyphen, <jats:styled-content style=\"fixed-case\">SIFT<\/jats:styled-content>, Mutationtaster and <jats:styled-content style=\"fixed-case\">SNAP<\/jats:styled-content> prediction sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighteen different heterozygous non\u2010synonymous <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>2<\/jats:italic> variants were identified in 24 patients. Twenty\u2010three patients had <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content> and one had <jats:styled-content style=\"fixed-case\">IGHD<\/jats:styled-content>. Two patients had additional diabetes insipidus, indicating deficiencies of anterior and posterior pituitary lobes. The posterior pituitary lobe on <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> was ectopic in 16, not visible in 4, normally placed in 2 and imaging was not available in two patients, but there were no signs of holoprosencephaly. Sixteen <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>2<\/jats:italic> variants were considered deleterious in at least one of the prediction sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A relatively high frequency of non\u2010synonymous <jats:italic><jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>2<\/jats:italic> variants was identified in patients with congenital <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> deficiency without other brain defects, and most of these patients presented with <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content> and an ectopic posterior pituitary lobe. <jats:italic>In vitro<\/jats:italic> functional assays may contribute to ascertain the deleterious consequences of these variants.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12044","type":"journal-article","created":{"date-parts":[[2012,9,11]],"date-time":"2012-09-11T22:39:50Z","timestamp":1347403190000},"page":"551-557","source":"Crossref","is-referenced-by-count":34,"title":["Relatively high frequency of non\u2010synonymous <i><scp>GLI<\/scp>2<\/i> variants in patients with congenital hypopituitarism without holoprosencephaly"],"prefix":"10.1111","volume":"78","author":[{"given":"Marcela M.","family":"Fran\u00e7a","sequence":"first","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laboratorio de Hormonios e Genetica Molecular LIM\/42 Disciplina de Endocrinologia Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A. L.","family":"Jorge","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laboratorio de Hormonios e Genetica Molecular LIM\/42 Disciplina de Endocrinologia Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciani R. S.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laboratorio de Hormonios e Genetica Molecular LIM\/42 Disciplina de Endocrinologia Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Everlayny F.","family":"Costalonga","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laboratorio de Hormonios e Genetica Molecular LIM\/42 Disciplina de Endocrinologia Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline P.","family":"Otto","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laboratorio de Hormonios e Genetica Molecular LIM\/42 Disciplina de Endocrinologia Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda A.","family":"Correa","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laboratorio de Hormonios e Genetica Molecular LIM\/42 Disciplina de Endocrinologia Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berenice B.","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laboratorio de Hormonios e Genetica Molecular LIM\/42 Disciplina de Endocrinologia Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo J. 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