{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:23:31Z","timestamp":1790839411078,"version":"4.1.0"},"reference-count":46,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>\n                    Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. The role of\n                    <jats:italic>MKRN3<\/jats:italic>\n                    , an imprinted gene located in the Prader\u2013Willi syndrome critical region (chromosome 15q11\u201313), in pubertal initiation was first described in 2013 after the identification of deleterious\n                    <jats:italic>MKRN3<\/jats:italic>\n                    mutations in five families with central precocious puberty (CPP) using whole-exome sequencing analysis. Since then, additional loss-of-function mutations of\n                    <jats:italic>MKRN3<\/jats:italic>\n                    have been associated with the inherited premature sexual development phenotype in girls and boys from different ethnic groups. In all of these families, segregation analysis clearly demonstrated autosomal dominant inheritance with complete penetrance, but with exclusive paternal transmission, consistent with the monoallelic expression of\n                    <jats:italic>MK<\/jats:italic>\n                    <jats:italic>RN3<\/jats:italic>\n                    (a maternally imprinted gene). Interestingly, the hypothalamic\n                    <jats:italic>Mkrn3<\/jats:italic>\n                    mRNA expression pattern in mice correlated with a putative inhibitory input on puberty initiation. Indeed, the initiation of puberty depends on a decrease in factors that inhibit the release of GnRH combined with an increase in stimulatory factors. These recent human and animal findings suggest that\n                    <jats:italic>MKRN3<\/jats:italic>\n                    plays an inhibitory role in the reproductive axis to represent a new pathway in pubertal regulation.\n                  <\/jats:p>","DOI":"10.1530\/jme-14-0315","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T21:23:11Z","timestamp":1431120191000},"page":"R131-R139","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":111,"title":["A new pathway in the control of the initiation of puberty: the MKRN3 gene"],"prefix":"10.1530","volume":"54","author":[{"given":"Ana Paula","family":"Abreu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delanie B","family":"Macedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius N","family":"Brito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula B","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"1_47517242","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1056\/NEJMoa1302160","volume":"368","year":"2013","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"13","key":"2_16847344","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1101\/gad.11.13.1703","volume":"11","author":"Barabino","year":"1997","journal-title":"Genes &amp; 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