{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:25:57Z","timestamp":1761513957835,"version":"3.37.3"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T00:00:00Z","timestamp":1490832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["SNF 31003A 153328"],"award-info":[{"award-number":["SNF 31003A 153328"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE\u201013686"],"award-info":[{"award-number":["R01 DE\u201013686"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (<jats:styled-content style=\"fixed-case\">CHH<\/jats:styled-content>), a rare genetic disorder caused by <jats:styled-content style=\"fixed-case\">gonadotropin\u2010releasing hormone<\/jats:styled-content> deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5\u2009months showed low testosterone (0.3\u2009nmol\/L) and undetectable gonadotropins (luteinizing hormone and follicle\u2010stimulating hormone both &lt;0.5\u2009U\/L), suggestive of <jats:styled-content style=\"fixed-case\">CHH<\/jats:styled-content>. Genetic testing identified a <jats:italic>de novo<\/jats:italic>, heterozygous mutation in fibroblast growth factor receptor 1 (<jats:italic><jats:styled-content style=\"fixed-case\">FGFR1<\/jats:styled-content><\/jats:italic> p.<jats:styled-content style=\"fixed-case\">L630P<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">L630<\/jats:styled-content> resides on the <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> binding cleft of the <jats:styled-content style=\"fixed-case\">FGFR1<\/jats:styled-content> tyrosine kinase domain, and <jats:styled-content style=\"fixed-case\">L630P<\/jats:styled-content> is predicted to cause a complete loss of receptor function. Cell\u2010based assays confirmed that <jats:styled-content style=\"fixed-case\">L630P<\/jats:styled-content> abolishes <jats:styled-content style=\"fixed-case\">FGF8<\/jats:styled-content> signaling activity. Identification of a loss\u2010of\u2010function <jats:italic>de novo <jats:styled-content style=\"fixed-case\">FGFR1<\/jats:styled-content><\/jats:italic> mutation in this patient confirms the diagnosis of <jats:styled-content style=\"fixed-case\">CHH<\/jats:styled-content>, allowing for a timely hormonal treatment to induce pubertal development. Therefore, genetic testing can complement clinical and hormonal assessment for a timely diagnosis of <jats:styled-content style=\"fixed-case\">CHH<\/jats:styled-content> in childhood.<\/jats:p>","DOI":"10.1111\/cge.12996","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T10:56:43Z","timestamp":1487069803000},"page":"213-216","source":"Crossref","is-referenced-by-count":14,"title":["Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism"],"prefix":"10.1111","volume":"92","author":[{"given":"C.","family":"Xu","sequence":"first","affiliation":[{"name":"Endocrinology, Diabetology &amp; Metabolism Service Lausanne University Hospital  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Lang\u2010Muritano","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Department University Children's Hospital  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Phan\u2010Hug","sequence":"additional","affiliation":[{"name":"Endocrinology\u2010Diabetology Unit, Department of Paediatrics Lausanne University Hospital  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.A.","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology &amp; Metabolism Service Lausanne University Hospital  Lausanne Switzerland"},{"name":"Institute of Higher Education and Research in Healthcare University of Lausanne  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.P.","family":"Sykiotis","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology &amp; Metabolism Service Lausanne University Hospital  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Cassatella","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology &amp; Metabolism Service Lausanne University Hospital  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"J.","family":"Acierno","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology &amp; Metabolism Service Lausanne University Hospital  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Pharmacology New York University School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-3237","authenticated-orcid":false,"given":"N.","family":"Pitteloud","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology &amp; Metabolism Service Lausanne University Hospital  Lausanne Switzerland"},{"name":"Endocrinology\u2010Diabetology Unit, Department of Paediatrics Lausanne University Hospital  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.112"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2465"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.164"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1210\/jcem.85.12.7058","article-title":"A possible role for reproductive hormones in newborn boys: progressive hypogonadism without the postnatal testosterone peak","volume":"85","author":"Main KM","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78448"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0179"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq559"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr330"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13633-016-0031-9"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0287-9"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.166"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2292"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34538"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12996","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12996","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T05:20:40Z","timestamp":1694323240000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,30]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1111\/cge.12996"],"URL":"https:\/\/doi.org\/10.1111\/cge.12996","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"type":"print","value":"0009-9163"},{"type":"electronic","value":"1399-0004"}],"subject":[],"published":{"date-parts":[[2017,3,30]]}}}