{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T21:49:23Z","timestamp":1783288163907,"version":"3.54.6"},"reference-count":64,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R00 HD091381"],"award-info":[{"award-number":["R00 HD091381"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HD019938"],"award-info":[{"award-number":["R01 HD019938"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HD082314"],"award-info":[{"award-number":["R01 HD082314"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21 HD098684"],"award-info":[{"award-number":["R21 HD098684"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K08 100595"],"award-info":[{"award-number":["K08 100595"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005292","name":"Brigham and Women's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005292","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Loss-of-function mutations in the maternally imprinted genes, MKRN3 and DLK1, are associated with central precocious puberty (CPP). Mutations in MKRN3 are the most common known genetic etiology of CPP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This work aimed to screen patients with CPP for MKRN3 and DLK1 mutations and analyze the effects of identified mutations on protein function in vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants included 84 unrelated children with CPP (79 girls, 5 boys) and, when available, their first-degree relatives. Five academic medical institutions participated. Sanger sequencing of MKRN3 and DLK1 5\u2032 upstream flanking and coding regions was performed on DNA extracted from peripheral blood leukocytes. Western blot analysis was performed to assess protein ubiquitination profiles.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Eight heterozygous MKRN3 mutations were identified in 9 unrelated girls with CPP. Five are novel missense mutations, 2 were previously identified in patients with CPP, and 1 is a frameshift variant not previously associated with CPP. No pathogenic variants were identified in DLK1. Girls with MKRN3 mutations had an earlier age of initial pubertal signs and higher basal serum luteinizing hormone and follicle-stimulating hormone compared to girls with CPP without MRKN3 mutations. Western blot analysis revealed that compared to wild-type MKRN3, mutations within the RING finger domain reduced ubiquitination whereas the mutations outside this domain increased ubiquitination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>MKRN3 mutations were present in 10.7% of our CPP cohort, consistent with previous studies. The novel identified mutations in different domains of MKRN3 revealed different patterns of ubiquitination, suggesting distinct molecular mechanisms by which the loss of MRKN3 results in early pubertal onset.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad151","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T10:25:20Z","timestamp":1678789520000},"page":"1646-1656","source":"Crossref","is-referenced-by-count":18,"title":["Novel <i>MKRN3<\/i> Missense Mutations Associated With Central Precocious Puberty Reveal Distinct Effects on Ubiquitination"],"prefix":"10.1210","volume":"108","author":[{"given":"John C","family":"Magnotto","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Mancini","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisha","family":"Bird","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Nemours Children's Health , Jacksonville, FL 32207 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Montenegro","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filiz","family":"T\u00fct\u00fcnc\u00fcler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Endocrinology Unit, Trakya University Faculty of Medicine , Edirne 22030 , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney A","family":"Pereira","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitoria","family":"Simas","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Garcia","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A","family":"Roberts","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Division of Endocrinology, Boston Children's Hospital , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delanie","family":"Macedo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Magnuson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Nemours Children's Health , Jacksonville, FL 32207 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Mauras","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Nemours Children's Health , Jacksonville, FL 32207 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma F","family":"Witchel","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh , Pittsburgh, PA 15224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rona S","family":"Carroll","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular\/LIM42, Hospital das Cl\u00ednicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-903 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula B","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5505-0852","authenticated-orcid":false,"given":"Ana Paula","family":"Abreu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"issue":"3","key":"2023112922382839500_dgad151-B1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/S2213-8587(15)00418-0","article-title":"Pubertal development and regulation","volume":"4","author":"Abreu","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"6","key":"2023112922382839500_dgad151-B2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nn.4298","article-title":"A microRNA switch regulates the rise in hypothalamic GnRH production before puberty","volume":"19","author":"Messina","year":"2016","journal-title":"Nat Neurosci"},{"issue":"3","key":"2023112922382839500_dgad151-B3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.tem.2008.10.005","article-title":"Kisspeptins and GnRH neuronal signalling","volume":"20","author":"Colledge","year":"2009","journal-title":"Trends Endocrinol Metab"},{"issue":"2","key":"2023112922382839500_dgad151-B4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.6065\/apem.2040094.047","article-title":"Minipuberty of human infancy\u2014a window of opportunity to evaluate hypogonadism and differences of sex development?","volume":"25","author":"Renault","year":"2020","journal-title":"Ann Pediatr Endocrinol Metab"},{"issue":"Suppl 2","key":"2023112922382839500_dgad151-B5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000058094","article-title":"The neuroendocrinology of human puberty revisited","volume":"57","author":"Grumbach","year":"2002","journal-title":"Horm Res Paediatr"},{"key":"2023112922382839500_dgad151-B6","first-page":"463","article-title":"The differential secretion of FSH and LH: regulation through genes, feedback and packaging","volume":"61","author":"McNeilly","year":"2003","journal-title":"Reprod Suppl"},{"issue":"4","key":"2023112922382839500_dgad151-B7","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s40272-015-0130-8","article-title":"Central precocious puberty: update on diagnosis and treatment","volume":"17","author":"Chen","year":"2015","journal-title":"Paediatr Drugs"},{"issue":"235","key":"2023112922382839500_dgad151-B8","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1136\/adc.44.235.291","article-title":"Variations in pattern of pubertal changes in girls","volume":"44","author":"Marshall","year":"1969","journal-title":"Arch Dis Child"},{"issue":"239","key":"2023112922382839500_dgad151-B9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1136\/adc.45.239.13","article-title":"Variations in the pattern of pubertal changes in boys","volume":"45","author":"Marshall","year":"1970","journal-title":"Arch Dis Child"},{"issue":"1","key":"2023112922382839500_dgad151-B10","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/ppe.12507","article-title":"Timing of puberty in boys and girls: a population-based study","volume":"33","author":"Brix","year":"2019","journal-title":"Paediatr Perinat Epidemiol"},{"issue":"3","key":"2023112922382839500_dgad151-B11","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/humupd\/7.3.292","article-title":"Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens","volume":"7","author":"Partsch","year":"2001","journal-title":"Hum Reprod Update"},{"key":"2023112922382839500_dgad151-B12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jpeds.2018.12.022","article-title":"Incidence and prevalence of central precocious puberty in Korea: an epidemiologic study based on a national database","volume":"208","author":"Kim","year":"2019","journal-title":"J Pediatr"},{"issue":"10","key":"2023112922382839500_dgad151-B13","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2020.15665","article-title":"Trends in the incidence of central precocious puberty and normal variant puberty among children in Denmark, 1998 to 2017","volume":"3","author":"Br\u00e4uner","year":"2020","journal-title":"JAMA Netw Open"},{"issue":"3","key":"2023112922382839500_dgad151-B14","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S2213-8587(15)00380-0","article-title":"Causes, diagnosis, and treatment of central precocious puberty","volume":"4","author":"Latronico","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"26","key":"2023112922382839500_dgad151-B15","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1056\/NEJMoa1302160","article-title":"Central precocious puberty caused by mutations in the imprinted gene MKRN3","volume":"368","author":"Abreu","year":"2013","journal-title":"N Engl J Med"},{"issue":"6247","key":"2023112922382839500_dgad151-B16","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/342281a0","article-title":"Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome","volume":"342","author":"Nicholls","year":"1989","journal-title":"Nature"},{"issue":"5","key":"2023112922382839500_dgad151-B17","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1093\/hmg\/8.5.795","article-title":"Imprinting of a RING zinc-finger encoding gene in the mouse chromosome region homologous to the Prader-Willi syndrome genetic region","volume":"8","author":"Jong","year":"1999","journal-title":"Hum Mol Genet"},{"issue":"5","key":"2023112922382839500_dgad151-B18","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/hmg\/8.5.783","article-title":"A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region","volume":"8","author":"Jong","year":"1999","journal-title":"Hum Mol Genet"},{"issue":"5","key":"2023112922382839500_dgad151-B19","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/ejhg.2008.232","article-title":"A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader-Willi syndrome","volume":"17","author":"Kanber","year":"2009","journal-title":"Eur J Hum Genet"},{"issue":"5","key":"2023112922382839500_dgad151-B20","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1210\/js.2019-00041","article-title":"MKRN3 mutations in central precocious puberty: a systematic review and meta-analysis","volume":"3","author":"Valadares","year":"2019","journal-title":"J Endocr Soc"},{"issue":"4","key":"2023112922382839500_dgad151-B21","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1210\/clinem\/dgaa955","article-title":"Genotype-phenotype correlations in central precocious puberty caused by MKRN3 mutations","volume":"106","author":"Seraphim","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2023112922382839500_dgad151-B22","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1093\/humrep\/deu256","article-title":"A novel MKRN3 missense mutation causing familial precocious puberty","volume":"29","author":"de Vries","year":"2014","journal-title":"Hum Reprod"},{"key":"2023112922382839500_dgad151-B23","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2021.663746","article-title":"A novel loss-of-function MKRN3 variant in a Chinese patient with familial precocious puberty: a case report and functional study","volume":"12","author":"Yin","year":"2021","journal-title":"Front Genet"},{"issue":"2","key":"2023112922382839500_dgad151-B24","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1159\/000362815","article-title":"MKRN3 mutations in familial central precocious puberty","volume":"82","author":"Schreiner","year":"2014","journal-title":"Horm Res Paediatr"},{"issue":"1","key":"2023112922382839500_dgad151-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/EJE-15-0488","article-title":"Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty","volume":"174","author":"Simon","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"2023112922382839500_dgad151-B26","doi-asserted-by":"crossref","DOI":"10.1210\/clinem\/dgac763","article-title":"Clinical and genetic characterization of familial central precocious puberty","volume":"108","author":"Tinano","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2023112922382839500_dgad151-B27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13052-020-0808-6","article-title":"MKRN3 and KISS1R mutations in precocious and early puberty","volume":"46","author":"Pagani","year":"2020","journal-title":"Ital J Pediatr"},{"issue":"3","key":"2023112922382839500_dgad151-B28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.14341\/probl12745","article-title":"Clinical and molecular genetic features of 3 family cases of the central precocious puberty, due to MKRN3 gene defects [article in Russian]","volume":"67","author":"Zubkova","year":"2021","journal-title":"Probl Endocrinol (Mosk)"},{"issue":"2","key":"2023112922382839500_dgad151-B29","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41390-020-01270-z","article-title":"Familial central precocious puberty: two novel MKRN3 mutations","volume":"90","author":"Varimo","year":"2021","journal-title":"Pediatr Res"},{"issue":"38","key":"2023112922382839500_dgad151-B30","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000022295","article-title":"A novel heterozygous MKRN3 nonsense mutation in a Chinese girl with idiopathic central precocious puberty: a case report","volume":"99","author":"Liu","year":"2020","journal-title":"Medicine (Baltimore)"},{"issue":"1","key":"2023112922382839500_dgad151-B31","doi-asserted-by":"crossref","DOI":"10.1016\/j.beem.2022.101618","article-title":"Genetics of pubertal timing","volume":"36","author":"Mancini","year":"2022","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"2","key":"2023112922382839500_dgad151-B32","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1210\/endrev\/bnac020","article-title":"The congenital and acquired mechanisms implicated in the etiology of central precocious puberty","volume":"44","author":"Brito","year":"2022","journal-title":"Endocr Rev"},{"issue":"1","key":"2023112922382839500_dgad151-B33","doi-asserted-by":"crossref","DOI":"10.1210\/jendso\/bvac168","article-title":"Six novel variants in the MKRN3 gene causing central precocious puberty","volume":"7","author":"Gernay","year":"2022","journal-title":"J Endocr Soc"},{"issue":"8","key":"2023112922382839500_dgad151-B34","first-page":"4486","article-title":"MKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons","volume":"130","author":"Abreu","year":"2020","journal-title":"J Clin Invest"},{"issue":"26","key":"2023112922382839500_dgad151-B35","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1056\/NEJMe1306743","article-title":"Releasing the brake on puberty","volume":"368","author":"Hughes","year":"2013","journal-title":"N Engl J Med"},{"key":"2023112922382839500_dgad151-B36","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.991322","article-title":"MKRN3 role in regulating pubertal onset: the state of art of functional studies","volume":"13","author":"Palumbo","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"2023112922382839500_dgad151-B37","doi-asserted-by":"crossref","first-page":"R131","DOI":"10.1530\/JME-14-0315","article-title":"A new pathway in the control of the initiation of puberty: the MKRN3 gene","volume":"54","author":"Abreu","year":"2015","journal-title":"J Mol Endocrinol"},{"issue":"9","key":"2023112922382839500_dgad151-B38","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/cdd.2011.16","article-title":"Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms","volume":"18","author":"de Bie","year":"2011","journal-title":"Cell Death Differ"},{"issue":"3","key":"2023112922382839500_dgad151-B39","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/nsr\/nwaa023","article-title":"MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3","volume":"7","author":"Li","year":"2020","journal-title":"Natl Sci Rev"},{"issue":"7","key":"2023112922382839500_dgad151-B40","doi-asserted-by":"crossref","first-page":"3796","DOI":"10.1093\/nar\/gkab155","article-title":"MKRN3-mediated ubiquitination of poly(A)-binding proteins modulates the stability and translation of GNRH1 mRNA in mammalian puberty","volume":"49","author":"Li","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2023112922382839500_dgad151-B41","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1210\/jc.2016-3677","article-title":"Paternally inherited DLK1 deletion associated with familial central precocious puberty","volume":"102","author":"Dauber","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2023112922382839500_dgad151-B42","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1055\/s-0039-3400963","article-title":"DLK1, Notch signaling and the timing of puberty","volume":"37","author":"Macedo","year":"2019","journal-title":"Semin Reprod Med"},{"issue":"8","key":"2023112922382839500_dgad151-B43","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1136\/jmedgenet-2014-102396","article-title":"Temple syndrome: improving the recognition of an underdiagnosed chromosome 14 imprinting disorder: an analysis of 51 published cases","volume":"51","author":"Ioannides","year":"2014","journal-title":"J Med Genet"},{"issue":"12","key":"2023112922382839500_dgad151-B44","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1038\/gim.2017.53","article-title":"Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients","volume":"19","author":"Kagami","year":"2017","journal-title":"Genet Med"},{"issue":"6","key":"2023112922382839500_dgad151-B45","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1210\/jc.2018-02010","article-title":"DLK1 is a novel link between reproduction and metabolism","volume":"104","author":"Gomes","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2023112922382839500_dgad151-B46","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1210\/clinem\/dgaa461","article-title":"Novel genetic and biochemical findings of DLK1 in children with central precocious puberty: a Brazilian-Spanish study","volume":"105","author":"Montenegro","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2023112922382839500_dgad151-B47","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/ng.3841","article-title":"Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk","volume":"49","author":"Day","year":"2017","journal-title":"Nat Genet"},{"issue":"7520","key":"2023112922382839500_dgad151-B48","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13545","article-title":"Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche","volume":"514","author":"Perry","year":"2014","journal-title":"Nature"},{"issue":"2","key":"2023112922382839500_dgad151-B49","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1530\/EJE-20-0862","article-title":"Prevalence and clinical characteristics of isolated forms of central precocious puberty: a cohort study at a single academic center","volume":"184","author":"Harbulot","year":"2021","journal-title":"Eur J Endocrinol"},{"key":"2023112922382839500_dgad151-B50","author":"Magnotto"},{"issue":"11","key":"2023112922382839500_dgad151-B51","doi-asserted-by":"crossref","first-page":"8399","DOI":"10.1007\/s13277-015-3607-8","article-title":"Serum DLK1 is a potential prognostic biomarker in patients with hepatocellular carcinoma","volume":"36","author":"Li","year":"2015","journal-title":"Tumour Biol"},{"issue":"3","key":"2023112922382839500_dgad151-B52","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1177\/0300060513498669","article-title":"Detection of Delta-like 1 ligand for the diagnosis of tuberculous meningitis: an effective and rapid diagnostic method","volume":"42","author":"Peng","year":"2014","journal-title":"J Int Med Res"},{"key":"2023112922382839500_dgad151-B53","author":"Magnotto"},{"issue":"6","key":"2023112922382839500_dgad151-B54","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/pr.2015.159","article-title":"A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty","volume":"78","author":"K\u00e4ns\u00e4koski","year":"2015","journal-title":"Pediatr Res"},{"issue":"4","key":"2023112922382839500_dgad151-B55","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods"},{"issue":"4","key":"2023112922382839500_dgad151-B56","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat Methods"},{"issue":"9","key":"2023112922382839500_dgad151-B57","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1101\/gr.772403","article-title":"PANTHER: a library of protein families and subfamilies indexed by function","volume":"13","author":"Thomas","year":"2003","journal-title":"Genome Res"},{"key":"2023112922382839500_dgad151-B58","author":"Magnotto"},{"issue":"6","key":"2023112922382839500_dgad151-B59","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/ng.2968","article-title":"The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome","volume":"46","author":"Stelzer","year":"2014","journal-title":"Nat Genet"},{"issue":"1","key":"2023112922382839500_dgad151-B60","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000446963","article-title":"High frequency of MKRN3 mutations in male central precocious puberty previously classified as idiopathic","volume":"105","author":"Bessa","year":"2017","journal-title":"Neuroendocrinology"},{"issue":"6","key":"2023112922382839500_dgad151-B61","doi-asserted-by":"crossref","first-page":"e2413","DOI":"10.1210\/clinem\/dgab123","article-title":"Pregnancy serum DLK1 concentrations are associated with indices of insulin resistance and secretion","volume":"106","author":"Petry","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2023112922382839500_dgad151-B62","doi-asserted-by":"crossref","first-page":"E1097","DOI":"10.1210\/jc.2013-3126","article-title":"Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3","volume":"99","author":"Macedo","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2023112922382839500_dgad151-B63","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1158\/1541-7786.MCR-08-0094","article-title":"Autoubiquitination of BCA2 RING E3 ligase regulates its own stability and affects cell migration","volume":"6","author":"Amemiya","year":"2008","journal-title":"Mol Cancer Res"},{"issue":"7-8","key":"2023112922382839500_dgad151-B64","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1159\/000504446","article-title":"Outcomes of patients with central precocious puberty due to loss-of-function mutations in the MKRN3 gene after treatment with gonadotropin-releasing hormone analog","volume":"110","author":"Ramos","year":"2020","journal-title":"Neuroendocrinology"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgad151\/49720097\/dgad151.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/7\/1646\/53940315\/dgad151.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/108\/7\/1646\/53940315\/dgad151.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T22:42:58Z","timestamp":1701297778000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/108\/7\/1646\/7077020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,14]]},"references-count":64,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,3,14]]},"published-print":{"date-parts":[[2023,6,16]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgad151","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,7]]},"published":{"date-parts":[[2023,3,14]]}}}