{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:39:29Z","timestamp":1790818769096,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","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"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","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\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["140289\/2020-8"],"award-info":[{"award-number":["140289\/2020-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/12205-2\/2022\/04870-9"],"award-info":[{"award-number":["2021\/12205-2\/2022\/04870-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["19\/27631-7"],"award-info":[{"award-number":["19\/27631-7"]}],"id":[{"id":"10.13039\/501100001807","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":["303183\/2020-9"],"award-info":[{"award-number":["303183\/2020-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HD082314"],"award-info":[{"award-number":["R01 HD082314"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NIH R01 HD019938"],"award-info":[{"award-number":["NIH R01 HD019938"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21 HD098684"],"award-info":[{"award-number":["R21 HD098684"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Several rare loss-of-function mutations of delta-like noncanonical notch ligand 1 (DLK1) have been described in non-syndromic children with familial central precocious puberty (CPP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We investigated genetic abnormalities of DLK1 gene in a French cohort of children with idiopathic CPP. Additionally, we explored the pattern of DLK1 serum levels in patients with CPP and in healthy children at puberty, as well as in wild-type female mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Genomic DNA was obtained from 121 French index cases with CPP. Automated sequencing of the coding region of the DLK1 gene was performed in all cases. Serum DLK1 levels were measured by enzyme linked immunosorbent assay (ELISA) in 209 individuals, including 191 with normal pubertal development and in female mice during postnatal pubertal maturation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 2 rare pathogenic DLK1 allelic variants: A stop gain variant (c.372C&amp;gt;A; p.Cys124X) and a start loss variant (c.2T&amp;gt;G; p.Met1?, or p.0) in 2 French girls with CPP. Mean serum DLK1 levels were similar between healthy children and idiopathic CPP children. In healthy individuals, DLK1 levels correlated with pubertal stage: In girls, DLK1 decreased between Tanner stages III and V, whereas in boys, DLK1 decreased between Tanner stages II and V (P = .008 and .016, respectively). Serum levels of Dlk1 also decreased in wild-type female mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Novel loss-of-function mutations in DLK1 gene were identified in 2 French girls with CPP. Additionally, we demonstrated a pattern of dynamic changes in circulating DLK1 serum levels in humans and mice during pubertal stages, reinforcing the role of this factor in pubertal timing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvad129","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T13:50:21Z","timestamp":1694613021000},"page":"422-428","source":"Crossref","is-referenced-by-count":19,"title":["Familial central precocious puberty due to DLK1 deficiency: novel genetic findings and relevance of serum DLK1 levels"],"prefix":"10.1093","volume":"189","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-7613","authenticated-orcid":false,"given":"Luciana","family":"Montenegro","sequence":"first","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo , S\u00e3o Paulo, 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Seraphim","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo , S\u00e3o Paulo, 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via","family":"Tinano","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo , S\u00e3o Paulo, 05403-000 ,","place":["Brazil"]},{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 021115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiara","family":"Piovesan","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo , S\u00e3o Paulo, 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana P M","family":"Canton","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo , S\u00e3o Paulo, 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"McElreavey","sequence":"additional","affiliation":[{"name":"Human Developmental Genetics Unit, Institute Pasteur , Paris, 75724 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Brabant","sequence":"additional","affiliation":[{"name":"Assistance Publique Hopitaux de Paris, Department of Functional Explorations, Necker Enfants Malades Hospital, Paris-Centre University , Paris Cedex, 75015 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia P","family":"Boris","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital and Harvard 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of Pediatrics, Universidad Aut\u00f3noma de Madrid , Madrid, 28049 ,","place":["Spain"]},{"name":"Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa , Madrid, 28009 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III , Madrid, 28029 ,","place":["Spain"]},{"name":"IMDEA Food Institute, CEIUAM+CSIC , Madrid, 28049 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius N","family":"Brito","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo , S\u00e3o Paulo, 05403-000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4456-4508","authenticated-orcid":false,"given":"Raja","family":"Brauner","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, H\u00f4pital Fondation Adolphe de Rothschild and Universit\u00e9 Paris Cit\u00e9 , Paris, 75019 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-693X","authenticated-orcid":false,"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Departamento de Cl\u00ednica M\u00e9dica, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo , S\u00e3o Paulo, 05403-000 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