{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:38:40Z","timestamp":1790818720604,"version":"4.1.0"},"reference-count":25,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100005639","name":"Universidade de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["13\/03236-5"],"award-info":[{"award-number":["13\/03236-5"]}],"id":[{"id":"10.13039\/501100005639","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005639","name":"Universidade de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/23892-5"],"award-info":[{"award-number":["2017\/23892-5"]}],"id":[{"id":"10.13039\/501100005639","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":["403525\/2016-0"],"award-info":[{"award-number":["403525\/2016-0"]}],"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","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI019\/0166"],"award-info":[{"award-number":["PI019\/0166"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIBER de fisiopatolog\u00eda y nutrici\u00f3n"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Central precocious puberty (CPP) has been associated with loss-of-function mutations in 2 paternally expressed genes (MKRN3 and DLK1). Rare defects in the DLk1 were also associated with poor metabolic phenotype at adulthood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our aim was to investigate genetic and biochemical aspects of DLK1 in a Spanish cohort of children with CPP without MKRN3 mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>A large cohort of children with idiopathic CPP (Spanish PUBERE Registry) was studied. Genomic deoxyribonucleic acid was obtained from 444 individuals (168 index cases) with CPP and their close relatives. Automatic sequencing of MKRN3 and DLK1 genes were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five rare heterozygous mutations of MKRN3 were initially excluded in girls with familial CPP. A rare allelic deletion (c.401_404\u2005+\u20058del) in the splice site junction of DLK1 was identified in a Spanish girl with sporadic CPP. Pubertal signs started at 5.7 years. Her metabolic profile was normal. Familial segregation analysis showed that the DLK1 deletion was de novo in the affected child. Serum DLK1 levels were undetectable (&amp;lt;0.4 ng\/mL), indicating that the deletion led to complete lack of DLK1 production. Three others rare allelic variants of DLK1 were also identified (p.Asn134=; g.-222 C&amp;gt;A and g.-223 G&amp;gt;A) in 2 girls with CPP. However, both had normal DLK1 serum levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Loss-of-function mutations of DLK1 represent a rare cause of CPP, reinforcing a significant role of this factor in human pubertal timing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa461","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T10:02:19Z","timestamp":1594980139000},"page":"3165-3172","source":"Crossref","is-referenced-by-count":52,"title":["Novel Genetic and Biochemical Findings of DLK1 in Children with Central Precocious Puberty: A Brazilian\u2013Spanish Study"],"prefix":"10.1210","volume":"105","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, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 I","family":"Labarta","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, Department of Pediatrics, Hospital Universitario Miguel Servet, Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n , Zaragoza,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maira","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, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","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, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Corripio","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Department, Corporaci\u00f3 Parc Taul\u00ed Hospital Universitari, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed I3PT, Universitat Aut\u00f2noma de Barcelona , Sabadell,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Soriano-Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, Institute of Biomedical Research \u2013 Hospital Universitario Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid . Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Travieso-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universidad Aut\u00f3noma de Madrid. Departments of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, IMDEA Food Institute . Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Mart\u00edn-Rivada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universidad Aut\u00f3noma de Madrid. Departments of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, IMDEA Food Institute . Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Barrios","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universidad Aut\u00f3noma de Madrid. Departments of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Instituto de Investigaci\u00f3n La Princesa, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, IMDEA Food Institute . Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E","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, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"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, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"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, Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universidad Aut\u00f3noma de Madrid. 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