{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:29:09Z","timestamp":1777937349881,"version":"3.51.4"},"reference-count":16,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2018]]},"abstract":"<jats:p>Background: The development of gonadotropin-independent (peripheral) precocious puberty in male children with primary adrenal insufficiency (PAI) is consistent with a defect in the genes encoding for the enzymes involved in steroid hormone biosynthesis. Methods: Two young boys presented with peripheral precocious puberty followed by PAI. In both patients, the analysis of CYP21A2 gene encoding 21-hydroxylase was normal. As a second step, a targeted next-generation sequencing (NGS) was performed in both patients using a customized panel of congenital endocrine disor ders. Results: Case 1 had a new homozygous variant in the CYP11B1 gene (c.1121+5G&gt;A). Mutations of this gene cause congenital adrenal hyperplasia due to 11\u03b2-hydroxylase deficiency, an essential enzyme in the cortisol biosynthesis pathway. Case 2 showed a new hemizygous mutation in the NR0B1 gene (c.1091T&gt;G), which encodes for DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita [AHC] and critical region on the X chromosome gene 1). NR0B1 mutations cause X-linked AHC and hypogonadotropic hypogonadism. Pathogenicity prediction software defined both mutations as probably damaging. Conclusions: Peripheral precocious puberty was the atypical presentation of 2 rare genetic diseases. The use of NGS made the characterization of these 2 cases with similar clinical phenotypes caused by 2 different genetic defects possible.<\/jats:p>","DOI":"10.1159\/000492496","type":"journal-article","created":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T17:01:19Z","timestamp":1536080479000},"page":"203-211","source":"Crossref","is-referenced-by-count":17,"title":["Next-Generation Sequencing Identifies Different Genetic Defects in 2 Patients with Primary Adrenal Insufficiency and Gonadotropin-Independent Precocious Puberty"],"prefix":"10.1159","volume":"90","author":[{"given":"Chiara","family":"Guzzetti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Bizzarri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Pisaneschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2228-8271","authenticated-orcid":false,"given":"Mafalda","family":"Mucciolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Bellacchio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Ibba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Letizia","family":"Casula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandro","family":"Loche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Cappa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2018,9,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61684-0"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1159\/000488034"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-1189-x"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/372635a0"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.07.018"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/372672a0"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.9.7816"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2001-0804"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1159\/000208804"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)70767-7"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1136\/adc.51.3.170"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1002\/prot.23170"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1621082114"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1159\/000320701"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1159\/000448726"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2017-0003"}],"updated-by":[{"DOI":"10.1159\/000495448","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T00:00:00Z","timestamp":1536019200000}}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/hrp\/article-pdf\/90\/3\/203\/4018757\/000492496.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/hrp\/article-pdf\/90\/3\/203\/4018757\/000492496.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T12:55:25Z","timestamp":1745412925000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000492496"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018]]},"references-count":16,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,11,7]]},"published-print":{"date-parts":[[2018,11,12]]}},"URL":"https:\/\/doi.org\/10.1159\/000492496","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.7042556","asserted-by":"subject"},{"id-type":"doi","id":"10.1159\/000495448","asserted-by":"object"}]},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018]]}}}