{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T10:33:08Z","timestamp":1771669988170,"version":"3.50.1"},"reference-count":20,"publisher":"Endocrinology Research Centre","issue":"3","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p>Gonadotropin-dependent precocious puberty (central) is a condition resulting from the early (up to 8 years in girls and 9 years in boys) reactivation of the hypothalamic-pituitary-gonadal axis. An increase in the secretion of sex steroids by the gonads in this form is a consequence of the stimulation of the sex glands by gonadotropic hormones of the pituitary gland. In the absence of central nervous system abnormalities, CPP is classified as idiopathic and as familial in some cases, emphasizing the genetic origin of this disorder. Loss-of-function mutations in Makorin Ring Finger Protein 3 (<jats:italic>MKRN3<\/jats:italic>) are the most common identified genetic cause of central precocious puberty compared to sporadic cases. In the present study we performed the first descrition of 3 family cases of central precocious puberty duo to novel <jats:italic>MKRN3<\/jats:italic> gene mutation detected by NGS in the Russian Federation.<\/jats:p>","DOI":"10.14341\/probl12745","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T06:46:08Z","timestamp":1627022768000},"page":"55-61","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":5,"title":["Clinical and molecular genetic features of 3 family cases of the central precocious puberty, due to &lt;i&gt;MKRN3&lt;\/i&gt; gene defects"],"prefix":"10.14341","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-7831","authenticated-orcid":true,"given":"N. A.","family":"Zubkova","sequence":"first","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-5372","authenticated-orcid":true,"given":"A. A.","family":"Kolodkina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0412-7140","authenticated-orcid":true,"given":"N. A.","family":"Makretskaya","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9834-727X","authenticated-orcid":true,"given":"P. L.","family":"Okorokov","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4429-4664","authenticated-orcid":true,"given":"T. V.","family":"Pogoda","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1107-362X","authenticated-orcid":true,"given":"E. V.","family":"Vasiliev","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0520-9132","authenticated-orcid":true,"given":"V. M.","family":"Petrov","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-4841","authenticated-orcid":true,"given":"A. N.","family":"Tiulpakov","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre; Research Centre for Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Gajdos ZKZ, Hirschhorn JN, Palmert MR. What controls the timing of puberty? An update on progress from genetic investigation. Curr Opin Endocrinol Diabetes Obes. 2009;16(1):16-24. doi: https:\/\/doi.org\/10.1097\/MED.0b013e328320253c","DOI":"10.1097\/MED.0b013e328320253c"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Palmert MR, Boepple PA. Variation in the timing of puberty: clinical spectrum and genetic investigation. J Clin Endocrinol Metab. 2001;86(6):2364-2368. doi: https:\/\/doi.org\/10.1210\/jcem.86.6.7603.","DOI":"10.1210\/jcem.86.6.7603"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Teilmann G. Prevalence and Incidence of Precocious Pubertal Development in Denmark: An Epidemiologic Study Based on National Registries. Pediatrics. 2005;116(6):1323-1328. doi: https:\/\/doi.org\/10.1542\/peds.2005-0012","DOI":"10.1542\/peds.2005-0012"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Soriano-Guill\u00e9n L, Corripio R, Labarta JI, et al. Central Precocious Puberty in Children Living in Spain: Incidence, Prevalence, and Influence of Adoption and Immigration. J Clin Endocrinol Metab. 2010;95(9):4305-4313. doi: https:\/\/doi.org\/10.1210\/jc.2010-1025","DOI":"10.1210\/jc.2010-1025"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Palmert MR, Hirschhorn JN. Genetic approaches to stature, pubertal timing, and other complex traits. Mol Genet Metab. 2003;80(1-2):1-10. doi: https:\/\/doi.org\/10.1016\/s1096-7192(03)00107-0","DOI":"10.1016\/S1096-7192(03)00107-0"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Parent AS, Teilmann G, Juul A, et al. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev. 2003;24(5):668-693. doi: https:\/\/doi.org\/10.1210\/er.2002-0019","DOI":"10.1210\/er.2002-0019"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Aiello F, Cirillo G, Cassio A, et al. Molecular screening of PROKR2 gene in girls with idiopathic central precocious puberty. Ital J Pediatr. 2021;47(1):5. doi: https:\/\/doi.org\/10.1186\/s13052-020-00951-z","DOI":"10.1186\/s13052-020-00951-z"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Valadares LP, Meireles CG, De Toledo IP, et al. MKRN3 Mutations in Central Precocious Puberty: A Systematic Review and Meta-Analysis. J Endocr Soc. 2019;3(5):979-995. doi: https:\/\/doi.org\/10.1210\/js.2019-00041","DOI":"10.1210\/js.2019-00041"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Simon D, Ba I, Mekhail N, et al. Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty. Eur J Endocrinol. 2016;174(1):1-8. doi: https:\/\/doi.org\/10.1530\/EJE-15-0488","DOI":"10.1530\/EJE-15-0488"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164. doi: https:\/\/doi.org\/10.1093\/nar\/gkq603","DOI":"10.1093\/nar\/gkq603"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Richards S, Aziz N, Bale S, et al. ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424. doi: https:\/\/doi.org\/10.1038\/gim.2015.30","DOI":"10.1038\/gim.2015.30"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Ryzhkova OP, Kardymon OL, Prohorchuk EB, et al. Rukovodstvo po interpretatsii dannykh posledovatel\u2019nosti DNK cheloveka, poluchennykh metodami massovogo parallel\u2019nogo sekvenirovaniya (MPS) (redaktsiya 2018, versiya 2). Medical Genetics. 2019;18(2):3-23. (In Russ.). doi: https:\/\/doi.org\/10.25557\/2073-7998.2019.02.3-23","DOI":"10.25557\/2073-7998.2019.02.3-23"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Abreu AP, Dauber A, Macedo DB, et al. Central precocious puberty caused by mutations in the imprinted gene MKRN3. N Engl J Med. 2013;368(26):2467-2475. doi: https:\/\/doi.org\/10.1056\/NEJMoa1302160","DOI":"10.1056\/NEJMoa1302160"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Jong MT, Gray TA, Ji Y, et al. A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region. Hum Mol Genet. 1999;8(5):783-793. doi: https:\/\/doi.org\/10.1093\/hmg\/8.5.783","DOI":"10.1093\/hmg\/8.5.783"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Abreu AP, Macedo DB, Brito VN, et al. A new pathway in the control of the initiation of puberty: the MKRN3 gene. J Mol Endocrinol. 2015;54(3):R131-139. doi: https:\/\/doi.org\/10.1530\/JME-14-0315","DOI":"10.1530\/JME-14-0315"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Liu H, Kong X, Chen F. Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation. Oncotarget. 2017;8(49):85102-85109. doi: https:\/\/doi.org\/10.18632\/oncotarget.19347","DOI":"10.18632\/oncotarget.19347"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Macedo DB, Fran\u00e7a MM, Montenegro LR, et al. Central Precocious Puberty Caused by a Heterozygous Deletion in the MKRN3 Promoter Region. Neuroendocrinology. 2018;107(2):127-132. doi: https:\/\/doi.org\/10.1159\/000490059","DOI":"10.1159\/000490059"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Lu W, Wang J, Li C, et al. A novel mutation in 5\u2019-UTR of Makorin ring finger 3 gene associated with the familial precocious puberty. Acta Biochim Biophys Sin (Shanghai). 2018;50(12):1291-1293. doi: https:\/\/doi.org\/10.1093\/abbs\/gmy124","DOI":"10.1093\/abbs\/gmy124"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Aycan Z, Sava\u015f-Erdeve \u015e, \u00c7etinkaya S, et al. Investigation of MKRN3 Mutation in Patients with Familial Central Precocious Puberty. J Clin Res Pediatr Endocrinol. 2018;10(3):223-229. doi: https:\/\/doi.org\/10.4274\/jcrpe.5506","DOI":"10.4274\/jcrpe.5506"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Ramos CO, Macedo DB, Canton APM, et al. Outcomes of Patients with Central Precocious Puberty Due to Loss-of-Function Mutations in the MKRN3 Gene after Treatment with Gonadotropin-Releasing Hormone Analog. Neuroendocrinology. 2020;110(7-8):705-713. doi: https:\/\/doi.org\/10.1159\/000504446","DOI":"10.1159\/000504446"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/12745\/9945","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T11:01:28Z","timestamp":1671620488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/12745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,11]]},"references-count":20,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,7,22]]}},"URL":"https:\/\/doi.org\/10.14341\/probl12745","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"value":"2308-1430","type":"electronic"},{"value":"0375-9660","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5,11]]}}}