{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T04:07:41Z","timestamp":1749096461643,"version":"3.41.0"},"reference-count":29,"publisher":"Institute of Cytology and Genetics, SB RAS","issue":"3","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"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, OMIM 176400, 615346) is an autosomal dominant disorder caused by the premature reactivation of the hypothalamic-pituitary-gonadal axis. Genetic, epigenetic, and environmental factors play a decisive role in determining the timing of puberty. In recent years, genetic variants in the <jats:italic>KISS1<\/jats:italic>, <jats:italic>KISS1R<\/jats:italic>, <jats:italic>MKRN3<\/jats:italic>, and <jats:italic>DLK1<\/jats:italic> genes have been identified as genetic causes of PP. The <jats:italic>MKRN3<\/jats:italic> and <jats:italic>DLK1<\/jats:italic> genes are imprinted, and therefore epigenetic modifications, such as DNA methylation, which alter the expression of these genes, can also contribute to the development of PP. The aim of this study is to determine the methylation index of the imprinting centers of the <jats:italic>DLK1<\/jats:italic> and <jats:italic>MKRN3<\/jats:italic> genes in girls with a clinical presentation of PP. The methylation index of the imprinting centers of the <jats:italic>DLK1<\/jats:italic> and <jats:italic>MKRN3<\/jats:italic> genes was analyzed in a group of 45 girls (age 7.2 \u00b1 1.9 years) with a clinical presentation of PP and a normal karyotype using targeted massive parallel sequencing after sodium bisulfite treatment of DNA. The control group consisted of girls without PP (<jats:italic>n<\/jats:italic> = 15, age 7.9 \u00b1 1.6 years). No significant age differences were observed between the groups (<jats:italic>p <\/jats:italic>&gt; 0.8). Analysis of the methylation index of the imprinting centers of the <jats:italic>DLK1<\/jats:italic> and <jats:italic>MKRN3<\/jats:italic> genes revealed no significant differences between patients with PP and the control group. However, in the group of patients with isolated adrenarche, an increased methylation index of the imprinting center of the <jats:italic>MKRN3<\/jats:italic> gene was observed (72 \u00b1 7.84 <jats:italic>vs<\/jats:italic> 56.92 \u00b1 9.44 %, <jats:italic>p<\/jats:italic> = 0.005). In the group of patients with central PP, 3.8 % of patients showed a decreased methylation index of the imprinting center of the <jats:italic>DLK1<\/jats:italic> gene, and 11.5 % of probands had a decreased methylation index of the imprinting center of the <jats:italic>MKRN3<\/jats:italic> gene. Thus, this study demonstrates that not only genetic variants but also alterations in the methylation index of the imprinting centers of the <jats:italic>DLK1<\/jats:italic> and <jats:italic>MKRN3<\/jats:italic> genes can contribute to the development of PP.<\/jats:p>","DOI":"10.18699\/vjgb-25-47","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T06:35:06Z","timestamp":1749018906000},"page":"440-447","source":"Crossref","is-referenced-by-count":0,"title":["Methylation index of the DLK1 and MKRN3 genes  in precocious puberty"],"prefix":"10.18699","volume":"29","author":[{"given":"E. A.","family":"Sazhenova","sequence":"first","affiliation":[{"name":"Scientific Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O. Yu.","family":"Vasilyeva","sequence":"additional","affiliation":[{"name":"Scientific Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. A.","family":"Fedotov","sequence":"additional","affiliation":[{"name":"Scientific Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. B.","family":"Kankanam Pathiranage","sequence":"additional","affiliation":[{"name":"Tomsk State University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. D.","family":"Lobanov","sequence":"additional","affiliation":[{"name":"Siberian State Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0410. Yu.","family":"Sambyalova","sequence":"additional","affiliation":[{"name":"Scientific Center for Family Health and Human Reproduction Problems"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. E.","family":"Khramova","sequence":"additional","affiliation":[{"name":"Scientific Center for Family Health and Human Reproduction Problems"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. V.","family":"Rychkova","sequence":"additional","affiliation":[{"name":"Scientific Center for Family Health and Human Reproduction Problems"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. \u0410.","family":"Vasilyev","sequence":"additional","affiliation":[{"name":"Scientific Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences; Tomsk State University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. N.","family":"Lebedev","sequence":"additional","affiliation":[{"name":"Scientific Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7950","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Abi Habib W., Brioude F., Azzi S., Rossignol S., Linglart A., Sobrier M.-L., Giabicani \u00c9., Steunou V., Harbison M.D., Le Bouc Y., Netchine I. Transcriptional profiling at the DLK1\/MEG3 domain explains clinical overlap between imprinting disorders. Sci Adv. 2019;5:e9425. doi 10.1126\/sciadv.aau9425","DOI":"10.1126\/sciadv.aau9425"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Abreu A.P., Toro C.A., Song Y.B., Navarro V.M., Bosch M.A., Eren A., Liang J.N., Carroll R.S., Latronico A.C., Ronnekleiv O.K. 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