{"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":1789412912223,"version":"build-2803163510"},"reference-count":39,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"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","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","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","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Central precocious puberty (CPP) can have a familial form in approximately one-quarter of the children. The recognition of this inherited condition increased after the identification of autosomal dominant CPP with paternal transmission caused by mutations in the MKRN3 and DLK1 genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to characterize the inheritance and estimate the prevalence of familial CPP in a large multiethnic cohort; to compare clinical and hormonal features, as well as treatment response to GnRH analogs (GnRHa), in children with distinct modes of transmission; and to investigate the genetic basis of familial CPP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively studied 586 children with a diagnosis of CPP. Patients with familial CPP (n = 276) were selected for clinical and genetic analysis. Data from previous studies were grouped, encompassing sequencing of MKRN3 and DLK1 genes in 204 patients. Large-scale parallel sequencing was performed in 48 individuals from 34 families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The prevalence of familial CPP was estimated at 22%, with a similar frequency of maternal and paternal transmission. Pedigree analyses of families with maternal transmission suggested an autosomal dominant inheritance. Clinical and hormonal features, as well as treatment response to GnRHa, were similar among patients with different forms of transmission of familial CPP. MKRN3 loss-of-function mutations were the most prevalent cause of familial CPP, followed by DLK1 loss-of-function mutations, affecting, respectively, 22% and 4% of the studied families; both affected exclusively families with paternal transmission. Rare variants of uncertain significance were identified in CPP families with maternal transmission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We demonstrated a similar prevalence of familial CPP with maternal and paternal transmission. MKRN3 and DLK1 loss-of-function mutations were the major causes of familial CPP with paternal transmission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgac763","type":"journal-article","created":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T23:47:41Z","timestamp":1673135261000},"page":"1758-1767","source":"Crossref","is-referenced-by-count":21,"title":["Clinical and Genetic Characterization of Familial Central Precocious Puberty"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8547-6507","authenticated-orcid":false,"given":"Fl\u00e1via Rezende","family":"Tinano","sequence":"first","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , 05403-900 S\u00e3o Paulo ,","place":["Brasil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Pinheiro Machado","family":"Canton","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , 05403-900 S\u00e3o Paulo ,","place":["Brasil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana R","family":"Montenegro","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , 05403-900 S\u00e3o Paulo ,","place":["Brasil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"de Castro Leal","sequence":"additional","affiliation":[{"name":"Departamento de Sa\u00fade Integrada, Universidade do Estado do Par\u00e1 (UEPA) , Santar\u00e9m, 68040-090 Par\u00e1 ,","place":["Brasil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline G","family":"Faria","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , 05403-900 S\u00e3o Paulo ,","place":["Brasil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-9470","authenticated-orcid":false,"given":"Carlos E","family":"Seraphim","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , 05403-900 S\u00e3o Paulo 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,","place":["Brasil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice B","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , 05403-900 S\u00e3o Paulo ,","place":["Brasil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universidad Aut\u00f3noma de Madrid , 28049 Madrid ,","place":["Spain"]},{"name":"Departments of Paediatrics and Paediatric Endocrinology, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas , 28009 Madrid ,","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n La Princesa , 28009 Madrid ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fisiopatolog\u00eda de la 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