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A group of 156 Brazilian girls with idiopathic CPP (ICPP) was used as control group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventy-one patients (45 girls and 26 boys from 36 families) had 18 different loss-of-function MKRN3 mutations. Eight mutations were classified as severe (70% of patients). Among the 71 patients, first pubertal signs occurred at 6.2\u2005\u00b1\u20051.2 years in girls and 7.1\u2005\u00b1\u20051.5 years in boys. Girls with MKRN3 mutations had a shorter delay between puberty onset and first evaluation and higher follicle-stimulating hormone levels than ICPP. Patients with severe MKRN3 mutations had a greater bone age advancement than patients with missense mutations (2.3\u2005\u00b1\u20051.6 vs 1.6\u2005\u00b1\u20051.4 years, P\u2005=\u2005.048), and had higher basal luteinizing hormone levels (2.2\u2005\u00b1\u20051.8 vs 1.1\u2005\u00b1\u20051.1 UI\/L, P\u2005=\u2005.018) at the time of presentation. Computational protein modeling revealed that 60% of the missense mutations were predicted to cause protein destabilization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inherited premature activation of the reproductive axis caused by loss-of-function mutations of MKRN3 is clinically indistinct from ICPP. However, the type of genetic defect may affect bone age maturation and gonadotropin levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa955","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T17:49:51Z","timestamp":1609436991000},"page":"e1041-e1050","source":"Crossref","is-referenced-by-count":48,"title":["Genotype\u2013Phenotype Correlations in Central Precocious Puberty Caused by\n                    <i>MKRN3<\/i>\n                    Mutations"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-9470","authenticated-orcid":false,"given":"Carlos Eduardo","family":"Seraphim","sequence":"first","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Pinheiro Machado","family":"Canton","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"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 LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiara Ribeiro","family":"Piovesan","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delanie B","family":"Macedo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Cunha","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo , S\u00e3o 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Spanish PUBERE Registry , Sabadell,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 I","family":"Labarta","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, Department of Pediatrics, Hospital Universitario Miguel Servet, Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n, Spanish PUBERE Registry , Zaragoza,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Travieso-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, Department of Endocrinology and Department of Pediatrics, Universidad Aut\u00f3noma de Madrid, Spanish PUBERE Registry, CIBER of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, IMDEA Institute , Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelmar 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