{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:38:29Z","timestamp":1783478309347,"version":"3.55.0"},"reference-count":26,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Idiopathic central precocious puberty (iCPP) is defined by the premature reactivation of the hypothalamic-pituitary-gonadal axis with normal magnetic resonance imaging scan of the central nervous system, causing the development of secondary sexual characteristics before age 8 years in girls and 9 years in boys. MKRN3 loss of function variants now represent the most common genetic cause of iCPP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This work aims to document the clinical course of puberty in 8 families harboring pathogenic MKRN3 variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This is an observational case series study of patients with CPP due to MKRN3 variants followed in a single center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Genetic analysis of MKRN3 was carried out in 28 unrelated patients with iCPP and a family history of paternal inheritance or no\/unavailable maternal inheritance, particularly in case of very early and rapidly evolving CPP. We identified 6 novel and 2 recently described variants in the MKRN3 gene in 9 girls, 1 boy, and their family members. These mutations were all predicted to be deleterious by in silico prediction programs<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We have identified 6 novel MKRN3 mutations in children with CPP. An MKRN3 loss of function should be considered after careful history pinpointing paternally inherited CPP. A family segregation study allowed the detection of an MKRN3 variant in 2 young brothers still prepubertal, raising the question of screening and management of asymptomatic prepubertal family members.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvac168","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T05:10:31Z","timestamp":1667538631000},"source":"Crossref","is-referenced-by-count":10,"title":["Six Novel Variants in the <i>MKRN3<\/i> Gene Causing Central Precocious Puberty"],"prefix":"10.1210","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0966-9523","authenticated-orcid":false,"given":"Caroline","family":"Gernay","sequence":"first","affiliation":[{"name":"Paediatric Endocrinology Unit, H\u00f4pital Universitaire des Enfants Reine Fabiola, Universit\u00e9 Libre de Bruxelles , 1020 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Brachet","sequence":"additional","affiliation":[{"name":"Paediatric Endocrinology Unit, H\u00f4pital Universitaire des Enfants Reine Fabiola, Universit\u00e9 Libre de Bruxelles , 1020 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emese","family":"Boros","sequence":"additional","affiliation":[{"name":"Paediatric Endocrinology Unit, H\u00f4pital Universitaire des Enfants Reine Fabiola, Universit\u00e9 Libre de Bruxelles , 1020 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Tenoutasse","sequence":"additional","affiliation":[{"name":"Paediatric Endocrinology Unit, H\u00f4pital Universitaire des Enfants Reine Fabiola, Universit\u00e9 Libre de Bruxelles , 1020 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Libioulle","sequence":"additional","affiliation":[{"name":"Department of Genetics, Centre Hospitalier Universitaire du Sart-Tilman, Universit\u00e9 de Li\u00e8ge , 4000 Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Heinrichs","sequence":"additional","affiliation":[{"name":"Paediatric Endocrinology Unit, H\u00f4pital Universitaire des Enfants Reine Fabiola, Universit\u00e9 Libre de Bruxelles , 1020 Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"issue":"4","key":"2022113011094841300_bvac168-B1","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1210\/jc.2003-030361","article-title":"Familial central precocious puberty suggests autosomal dominant inheritance","volume":"89","author":"de Vries","year":"2004","journal-title":"J 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