{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:35:38Z","timestamp":1787726138502,"version":"build-2784847793"},"reference-count":94,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","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":"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":["303183\/2020-9"],"award-info":[{"award-number":["303183\/2020-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD 082314-08"],"award-info":[{"award-number":["R01 HD 082314-08"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Ensino Superior","award":["88881.170070\/2018-01"],"award-info":[{"award-number":["88881.170070\/2018-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human puberty is a dynamic biological process determined by the increase in the pulsatile secretion of GnRH triggered by distinct factors not fully understood. Current knowledge reveals fine tuning between an increase in stimulatory factors and a decrease in inhibitory factors, where genetic and epigenetic factors have been indicated as key players in the regulation of puberty onset by distinct lines of evidence. Central precocious puberty (CPP) results from the premature reactivation of pulsatile secretion of GnRH. In the past decade, the identification of genetic causes of CPP has largely expanded, revealing hypothalamic regulatory factors of pubertal timing. Among them, 3 genes associated with CPP are linked to mechanisms involving DNA methylation, reinforcing the strong role of epigenetics underlying this disorder. Loss-of-function mutations in Makorin Ring-Finger Protein 3 (MKRN3) and Delta-Like Non-Canonical Notch Ligand 1 (DLK1), 2 autosomal maternally imprinted genes, have been described as relevant monogenic causes of CPP with the phenotype exclusively associated with paternal transmission. MKRN3 has proven to be a key component of the hypothalamic inhibitory input on GnRH neurons through different mechanisms. Additionally, rare heterozygous variants in the Methyl-CpG-Binding Protein 2 (MECP2), an X-linked gene that is a key factor of DNA methylation machinery, were identified in girls with sporadic CPP with or without neurodevelopmental disorders. In this mini-review, we focus on how the identification of genetic causes of CPP has revealed epigenetic regulators of human pubertal timing, summarizing the latest knowledge on the associations of puberty with MKRN3, DLK1, and MECP2.<\/jats:p>","DOI":"10.1210\/jendso\/bvae228","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T07:07:04Z","timestamp":1737443224000},"source":"Crossref","is-referenced-by-count":16,"title":["Genetics and Epigenetics of Human Pubertal Timing: The Contribution of Genes Associated With Central Precocious Puberty"],"prefix":"10.1210","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-5412","authenticated-orcid":false,"given":"Ana Pinheiro Machado","family":"Canton","sequence":"first","affiliation":[{"name":"Cellular and Molecular Endocrinology Laboratory LIM\/25, Division of Endocrinology and Metabolism, Clinicas Hospital, School of Medicine, University of Sao Paulo , 01246-903 Sao Paulo 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