{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T17:39:57Z","timestamp":1781545197702,"version":"3.54.5"},"reference-count":37,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T00:00:00Z","timestamp":1481241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T00:00:00Z","timestamp":1481241600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2017]]},"abstract":"<b><i>Background\/Aims:<\/i><\/b> Idiopathic central precocious puberty (ICPP) is the premature activation of the hypothalamic-pituitary-gonadal axis in the absence of organic disease. Up to now, just gain-of-function mutations of <i>KISS1\/KISS1R <\/i>and loss-of-function mutations of the maternally imprinted gene <i>MKRN3 <\/i>are the known genetic causes of ICPP. Our intention is to evaluate variants present in genes related to the pubertal onset pathway that could act as disease-causing or predisposing variants. <b><i>Methods:<\/i><\/b> We studied the clinical exome of 20 patients diagnosed with ICPP using the Illumina platform. The bioinformatics analysis was performed using 2 different programs, and the variants were filtered according to a list of genes related to the gonadotropin-releasing hormone pathway. <b><i>Results:<\/i><\/b> In a \u201csporadic case,\u201d we found a missense variant in <i>MKRN3<\/i> NM_005664.3: c.203G>A, causing the protein change NP_005655.1:p.Arg68His, predicted as pathogenic by 2 informatics tools. The proband carrying this variant was diagnosed with ICPP at 7.75 years of age. We did not find any pathogenic variants in <i>KISS1<\/i>,<i> KISS1R<\/i>, <i>LIN28<\/i>, <i>GNRH<\/i>, <i>GNRHR<\/i>, <i>TACR3<\/i>, and <i>TAC3<\/i>. <b><i>Conclusion:<\/i><\/b><i>MKRN3 <\/i>is the most frequent genetic cause of familial ICPP, so it is wise to screen for <i>MKRN3 <\/i>mutations in all patients with familial ICPP and in patients with an unclear paternal pubertal history.<\/jats:p>","DOI":"10.1159\/000453262","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T22:01:35Z","timestamp":1481234495000},"page":"88-94","source":"Crossref","is-referenced-by-count":28,"title":["Clinical Exome Sequencing Reveals <b><i>MKRN3<\/i><\/b> Pathogenic Variants in Familial and Nonfamilial Idiopathic Central Precocious Puberty"],"prefix":"10.1159","volume":"87","author":[{"given":"Nelmar 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