{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T11:40:03Z","timestamp":1744717203632,"version":"3.40.4"},"reference-count":31,"publisher":"Institute of Cytology and Genetics, SB RAS","issue":"2","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/vavilov.elpub.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vestn. VOGiS"],"abstract":"<jats:p>Precocious puberty (PP, E30.1, \u041522.8, \u041530.9 according to ICD 10, MIM 176400, 615346) in children is a disorder in which secondary sexual characteristics appear earlier than the age norm. The timing of puberty is regulated by a complex interaction of genetic and epigenetic factors, as well as environmental and nutritional factors. This study aimed to search for pathogenic, likely pathogenic variants or variants of uncertain significance (VUS) in the <jats:italic>KISS1, GPR54, DLK1<\/jats:italic>, and <jats:italic>MKRN3<\/jats:italic> genes in patients with the clinical picture of PP and normal karyotype by massive parallel sequencing. All identified genetic variants were confirmed by Sanger sequencing. The pathogenicity of identified genetic variants and the functional significance of the protein synthesized by them were analyzed according to recommendations for interpretation of NGS analysis results using online algorithms for pathogenicity prediction (Variant Effect Predictor, Franklin, Varsome, and PolyPhen2). Clinically significant genetic variants were detected in the heterozygous state in the <jats:italic>KISS1R, DLK1,<\/jats:italic> and <jats:italic>MKRN3<\/jats:italic> genes in 5 of 52 probands (9.6 %) with PP, including 3 of 33 (9.1 %) in the group with central PP and 2 of 19 (10.5 %) in the group with gonadotropin-independent PP. Two children with gonadotropin-independent PP had VUS in the <jats:italic>KISS1R<\/jats:italic> gene (c.191T&gt;C, p.Ile64Thr and c.233A&gt;G, p.Asn78Ser), one of which was inherited from the father and the second, from the mother. The remaining patients with central PP had likely pathogenic genetic variants: DLK1:c.373delC(p.Gln125fs) <jats:italic>de novo<\/jats:italic> and DLK1:c.480delT(p.Gly161Alafs*49) of paternal origin. The third proband had a VUS variant in the MKRN3 gene (c.1487A&gt;G, p.His496Arg), inherited from the father. All identified genetic variants were described for the first time in PP. Thus, in the present study, genetic variants in the <jats:italic>KISS1R, DLK1<\/jats:italic>, and <jats:italic>MKRN3<\/jats:italic> genes in girls with PP were characterized.<\/jats:p>","DOI":"10.18699\/vjgb-25-33","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T17:30:54Z","timestamp":1744651854000},"page":"301-309","source":"Crossref","is-referenced-by-count":0,"title":["Genetic variants of the DLK1, KISS1R, MKRN3 genes in girls with precocious puberty"],"prefix":"10.18699","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-3932","authenticated-orcid":true,"given":"E. A.","family":"Sazhenova","sequence":"first","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-0014","authenticated-orcid":true,"given":"O. Yu.","family":"Vasilyeva","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-5451","authenticated-orcid":true,"given":"E. A.","family":"Fonova","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9026-0582","authenticated-orcid":true,"given":"M. B.","family":"Kankanam Pathiranage","sequence":"additional","affiliation":[{"name":"Tomsk State University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-6282","authenticated-orcid":true,"given":"A. Yu.","family":"Sambyalova","sequence":"additional","affiliation":[{"name":"Scientific Center for Family Health and Human Reproduction Problems"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8042-6276","authenticated-orcid":true,"given":"E. E.","family":"Khramova","sequence":"additional","affiliation":[{"name":"Scientific Center for Family Health and Human Reproduction Problems"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-0737","authenticated-orcid":true,"given":"L. V.","family":"Rychkova","sequence":"additional","affiliation":[{"name":"Scientific Center for Family Health and Human Reproduction Problems"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5301-070X","authenticated-orcid":true,"given":"S. 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