{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:48:10Z","timestamp":1783392490841,"version":"3.54.6"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of <jats:italic>KISSR1<\/jats:italic> (previously named <jats:italic>GPR54<\/jats:italic>) and <jats:italic>MKRN3<\/jats:italic> genes on pubertal timing.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8\u2009years of age, and in 6 girls affected by early puberty (EP) between 8 and 10\u2009years of age.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Direct sequencing of the <jats:italic>KISS1R<\/jats:italic> (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the <jats:italic>GPR54<\/jats:italic> gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of <jats:italic>MKRN3<\/jats:italic> in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3\/13 CPP patients and 3\/6 EP patients) we found the synonymous variant c.663C\u2009&gt;\u2009T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In conclusion, we identified sequence variations of the <jats:italic>KISS1R<\/jats:italic> and <jats:italic>MKRN3<\/jats:italic> genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13052-020-0808-6","type":"journal-article","created":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T11:03:04Z","timestamp":1585566184000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["MKRN3 and KISS1R mutations in precocious and early puberty"],"prefix":"10.1186","volume":"46","author":[{"given":"Sara","family":"Pagani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Calcaterra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Acquafredda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Montalbano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bozzola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Ferrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Gasparri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Villani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4882-3714","authenticated-orcid":false,"given":"Mauro","family":"Bozzola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"808_CR1","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.3346\/jkms.2014.29.8.1120","volume":"29","author":"JY Rhie","year":"2014","unstructured":"Rhie JY, Lee KH, Ko JM, Lee WJ, Kim JH, Kim HS. 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All research was carried out in accordance with the Ethical Standards involving human participants. The study was approved by the \u201cComitato Etico Area di Pavia\u201d, the Ethics Committee of the Foundation IRCCS San Matteo Hospital, on 17th May, 2016 (reference number 20160005680). All participants provided parental written informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All participants provided parental written informed consent for publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39"}}