{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:08:32Z","timestamp":1789412912325,"version":"build-2803163510"},"reference-count":48,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2013]]},"abstract":"<b><i>Background\/Aim:<\/i><\/b> TTF1 and EAP1 are transcription factors that modulate gonadotropin-releasing hormone expression. We investigated the contribution of <i>TTF1<\/i> and <i>EAP1<\/i> genes to central pubertal disorders. <b><i>Patients and Methods:<\/i><\/b> 133 patients with central pubertal disorders were studied: 86 with central precocious puberty and 47 with normosmic isolated hypogonadotropic hypogonadism. The coding region of <i>TTF1<\/i> and <i>EAP1<\/i> were sequenced. Variations of polyglutamine and polyalanine repeats in EAP1 were analyzed by GeneScan software. Association of <i>TTF1<\/i> and <i>EAP1<\/i> to genes implicated in timing of puberty was investigated by meta-network framework GeneMANIA and Cytoscape software. <b><i>Results:<\/i><\/b> Direct sequencing of the <i>TTF1<\/i> did not reveal any mutation or polymorphisms. Four EAP1 synonymous variants were identified with similar frequencies among groups. The most common EAP1 5\u2032-distal polyalanine genotype was the homozygous 12\/12, but the genotype 12\/9 was identified in 2 central precocious puberty sisters without functional alteration in EAP1 transcriptional activity. TTF1 and EAP1 were connected, via genetic networks, to genes implicated in the control of menarche. <b><i>Conclusion:<\/i><\/b> No <i>TTF1 <\/i>or <i>EAP1 <\/i>germline mutations were associated with central pubertal disorders. <i>TTF1 <\/i>and <i>EAP1 <\/i>may affect puberty by changing expression in response to other members of puberty-associated gene networks, or by differentially affecting the expression of gene components of these networks.<\/jats:p>","DOI":"10.1159\/000354643","type":"journal-article","created":{"date-parts":[[2013,9,18]],"date-time":"2013-09-18T06:57:00Z","timestamp":1379487420000},"page":"257-266","source":"Crossref","is-referenced-by-count":16,"title":["Molecular and Gene Network Analysis of Thyroid Transcription Factor 1 <b><i>(TTF1)<\/i><\/b> and Enhanced at Puberty <b><i>(EAP1)<\/i><\/b> Genes in Patients with GnRH-Dependent Pubertal Disorders"],"prefix":"10.1159","volume":"80","author":[{"given":"Priscilla","family":"Cukier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hollis","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomke","family":"Rulfs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Ferreira Gontijo","family":"Silveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena Gurgel","family":"Teles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice Bilharinho","family":"Mendonca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo 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