{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T05:04:05Z","timestamp":1781327045544,"version":"3.54.1"},"reference-count":0,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2017]]},"abstract":"<b><i>Background\/Aims:<\/i><\/b> Recently, loss-of-function mutations in the <i>MKRN3<\/i> gene have been implicated in the etiology of familial central precocious puberty (CPP) in both sexes. We aimed to analyze the frequency of <i>MKRN3<\/i> mutations in boys with CPP and to compare the clinical and hormonal features of boys with and without <i>MKRN3<\/i> mutations. <b><i>Methods:<\/i><\/b> This was a retrospective review of clinical, hormonal and genetic features of 20 male patients with idiopathic CPP evaluated at an academic medical center. The entire coding regions of <i>MKRN3<\/i>, <i>KISS1 <\/i>and<i> KISS1R<\/i> genes were sequenced. <b><i>Results:<\/i><\/b> We studied 20 boys from 17 families with CPP. All of them had normal brain magnetic resonance imaging. Eight boys from 5 families harbored four<b> <\/b>distinct<b> <\/b>heterozygous MKRN3 mutations predicted to be deleterious for protein function, p.Ala162Glyfs*14, p.Arg213Glyfs*73, p.Arg328Cys and p.Arg365Ser. One boy carried a previously described KISS1-activating mutation (p.Pro74Ser). The frequency of <i>MKRN3<\/i> mutations among these boys with idiopathic CPP was significantly higher than previously reported female data (40 vs. 6.4%, respectively, p < 0.001). Boys with <i>MKRN3<\/i> mutations had typical clinical and hormonal features of CPP. Notably, they had later pubertal onset than boys without MKRN3 abnormalities (median age 8.2 vs. 7.0 years, respectively, p = 0.033). <b><i>Conclusion:<\/i><\/b> We demonstrated a high frequency of <i>MKRN3<\/i> mutations in boys with CPP, previously classified as idiopathic, suggesting the importance of genetic analysis in this group. The boys with CPP due to <i>MKRN3<\/i> mutations had classical features of CPP, but with puberty initiation at a borderline age.<\/jats:p>","DOI":"10.1159\/000446963","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T21:15:58Z","timestamp":1464210958000},"page":"17-25","source":"Crossref","is-referenced-by-count":69,"title":["High Frequency of <b><i>MKRN3<\/i><\/b> Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic"],"prefix":"10.1159","volume":"105","author":[{"given":"Danielle S.","family":"Bessa","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":"Monica M.","family":"Fran\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana R.","family":"Montenegro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Cunha-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia G.","family":"Silveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago","family":"Hummel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Bergad\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Braslavsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Abreu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4890-0262","authenticated-orcid":false,"given":"Andrew","family":"Dauber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-1084","authenticated-orcid":false,"given":"Berenice B.","family":"Mendonca","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":"127","published-online":{"date-parts":[[2016,5,26]]},"container-title":["Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/446963","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/446963","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:48:50Z","timestamp":1745426930000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000446963"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,26]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,6,6]]}},"URL":"https:\/\/doi.org\/10.1159\/000446963","archive":["Portico"],"relation":{},"ISSN":["0028-3835","1423-0194"],"issn-type":[{"value":"0028-3835","type":"print"},{"value":"1423-0194","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,26]]}}}