{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:38:12Z","timestamp":1790818692639,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2019\/27631-7"],"award-info":[{"award-number":["2019\/27631-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2022\/00719-4"],"award-info":[{"award-number":["2022\/00719-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2019\/26780-9"],"award-info":[{"award-number":["2019\/26780-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2014\/50137-5"],"award-info":[{"award-number":["2014\/50137-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2013\/08028-1"],"award-info":[{"award-number":["2013\/08028-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["303183\/2020-9"],"award-info":[{"award-number":["303183\/2020-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["307571\/2021-1"],"award-info":[{"award-number":["307571\/2021-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["142362\/2019-0"],"award-info":[{"award-number":["142362\/2019-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The etiology of central precocious puberty (CPP) has expanded with identification of new genetic causes, including the monogenic deficiency of Makorin-Ring-Finger-Protein-3 (MKRN3). We aimed to assess the prevalence of CPP causes and the predictors of genetic involvement in this phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A retrospective cohort study for an etiological survey of patients with CPP from a single academic center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>All patients with CPP had detailed medical history, phenotyping, and brain magnetic resonance imaging (MRI); those with negative brain MRI (apparently idiopathic) were submitted to genetic studies, mainly DNA sequencing studies, genomic microarray, and methylation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We assessed 270 patients with CPP: 50 (18.5%) had CPP-related brain lesions (34 [68%] congenital lesions), whereas 220 had negative brain MRI. Of the latter, 174 (165 girls) were included for genetic studies. Genetic etiologies were identified in 22 patients (20 girls), indicating an overall frequency of genetic CPP of 12.6% (22.2% in boys and 12.1% in girls). The most common genetic defects were MKRN3, Delta-Like-Non-Canonical-Notch-Ligand-1 (DLK1), and Methyl-CpG-Binding-Protein-2 (MECP2) loss-of-function mutations, followed by 14q32.2 defects (Temple syndrome). Univariate logistic regression identified family history (odds ratio [OR] 3.3; 95% CI 1.3-8.3; P = .01) and neurodevelopmental disorders (OR 4.1; 95% CI 1.3-13.5; P = .02) as potential clinical predictors of genetic CPP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Distinct genetic causes were identified in 12.6% patients with apparently idiopathic CPP, revealing the genetic etiology as a relevant cause of CPP in both sexes. Family history and neurodevelopmental disorders were suggested as predictors of genetic CPP. We originally proposed an algorithm to investigate the etiology of CPP including genetic studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae063","type":"journal-article","created":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T09:33:05Z","timestamp":1717839185000},"page":"479-488","source":"Crossref","is-referenced-by-count":14,"title":["The genetic etiology is a relevant cause of central precocious puberty"],"prefix":"10.1093","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-5412","authenticated-orcid":false,"given":"Ana Pinheiro Machado","family":"Canton","sequence":"first","affiliation":[{"name":"Developmental Endocrinology Unit, Hormones and Molecular Genetics Laboratory LIM\/42, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 05403-000 Sao Paulo ,","place":["Brazil"]},{"name":"Cellular and Molecular Endocrinology Laboratory LIM\/25, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 01246-903 Sao Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Eduardo","family":"Seraphim","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Unit, Hormones and Molecular Genetics Laboratory LIM\/42, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 05403-000 Sao Paulo ,","place":["Brazil"]},{"name":"Cellular and Molecular Endocrinology Laboratory LIM\/25, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 01246-903 Sao Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-7613","authenticated-orcid":false,"given":"Luciana Ribeiro","family":"Montenegro","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Unit, Hormones and Molecular Genetics Laboratory LIM\/42, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 05403-000 Sao Paulo ,","place":["Brazil"]},{"name":"Cellular and Molecular Endocrinology Laboratory LIM\/25, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 01246-903 Sao Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Victorino","family":"Krepischi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo , 05508-090 Sao Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice Bilharinho","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Unit, Hormones and Molecular Genetics Laboratory LIM\/42, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 05403-000 Sao Paulo ,","place":["Brazil"]},{"name":"Laborat\u00f3rio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina da Universidade de S\u00e3o Paulo , 01246-903 Sao Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Unit, Hormones and Molecular Genetics Laboratory LIM\/42, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 05403-000 Sao Paulo ,","place":["Brazil"]},{"name":"Cellular and Molecular Endocrinology Laboratory LIM\/25, Clinicas Hospital, Discipline of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo , 01246-903 Sao Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius 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