{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:00:28Z","timestamp":1783699228621,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T00:00:00Z","timestamp":1438819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004117","name":"A.G. 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Premature activation of the Gn<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> secretion in central precocious puberty (<jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>) may arise either from gain\u2010of\u2010function mutations of the <jats:italic><jats:styled-content style=\"fixed-case\">KISS<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">KISS<\/jats:styled-content>1R<\/jats:italic> genes or from loss\u2010of\u2010function manner mutations of the <jats:italic><jats:styled-content style=\"fixed-case\">MKRN<\/jats:styled-content>3<\/jats:italic> gene leading to <jats:styled-content style=\"fixed-case\">MKRN<\/jats:styled-content>3 deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore the genetic causes responsible for <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content> and the potential role of the <jats:styled-content style=\"fixed-case\">RING<\/jats:styled-content> finger protein 3 (<jats:italic><jats:styled-content style=\"fixed-case\">MKRN<\/jats:styled-content>3<\/jats:italic>) gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and patients<\/jats:title><jats:p>We investigated potential sequence variations in the intronless <jats:italic><jats:styled-content style=\"fixed-case\">MKRN<\/jats:styled-content>3<\/jats:italic> gene by Sanger sequencing of the entire 507 amino acid coding region of exon 1 in a family with two affected girls presented with <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content> at the age of 6 and 5\u00b77\u00a0years, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel heterozygous g.Gly312Asp missense mutation in the <jats:italic><jats:styled-content style=\"fixed-case\">MKRN<\/jats:styled-content>3<\/jats:italic> gene was identified in these siblings. The imprinted <jats:italic><jats:styled-content style=\"fixed-case\">MKRN<\/jats:styled-content>3<\/jats:italic> missense mutation was also identified as expected in the unaffected father and followed as expected an imprinted mode of inheritance. <jats:italic>In silico<\/jats:italic> analysis of the altered missense variant using the computational algorithms Polyphen2, <jats:styled-content style=\"fixed-case\">SIFT<\/jats:styled-content> and Mutation Taster predicted a damage and pathogenic alteration causing <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content>. The pathogenicity of the alteration at the protein level via an i<jats:italic>n silico<\/jats:italic> structural model is also explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A novel mutation in the <jats:italic><jats:styled-content style=\"fixed-case\">MKRN<\/jats:styled-content>3<\/jats:italic> gene in two sisters with <jats:styled-content style=\"fixed-case\">CPP<\/jats:styled-content> was identified, supporting the fundamental role of this gene in the suppression of the hypothalamic Gn<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> neurons.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12854","type":"journal-article","created":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T09:44:49Z","timestamp":1436953489000},"page":"80-84","source":"Crossref","is-referenced-by-count":31,"title":["In silico analysis of a novel <i><scp>MKRN<\/scp>3<\/i> missense mutation in familial central precocious 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