{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:53:58Z","timestamp":1753883638555,"version":"3.41.2"},"reference-count":10,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Congenital hypogonadotropic hypogonadism (CHH) can cause delayed secondary sexual characteristics and contribute to juvenile osteoporosis, with multiple causative genes having been reported. We treated a 27-year-old man diagnosed with central hypogonadism, presenting with delayed secondary sexual characteristics and juvenile osteoporosis, using bone resorption inhibitors and testosterone therapy. Genetic testing revealed missense variants both in the fibroblast growth factor receptor 1 (FGFR1) and gonadotropin-releasing hormone receptor (GNRHR) genes, a combination that has not been previously reported. This case represents a CHH caused by a novel combination of gene variants not registered in the human genome mutation database.<\/jats:p>","DOI":"10.1210\/jcemcr\/luae254","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T12:27:49Z","timestamp":1736944069000},"source":"Crossref","is-referenced-by-count":0,"title":["Congenital Hypogonadotropic Hypogonadism With Novel Pathogenic Variants in FGFR1 and GNRHR"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5617-7978","authenticated-orcid":false,"given":"Shinta","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto 602-8566 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-1790","authenticated-orcid":false,"given":"Hanako","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto 602-8566 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1707-970X","authenticated-orcid":false,"given":"Hiroshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto 602-8566 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto 602-8566 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8651-4445","authenticated-orcid":false,"given":"Masahide","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto 602-8566 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiaki","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto 602-8566 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"issue":"4","key":"2025012804210681400_luae254-B1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3803\/EnM.2015.30.4.456","article-title":"Congenital hypogonadotropic hypogonadism and Kallmann syndrome: past, present, and future","volume":"30","author":"Kim","year":"2015","journal-title":"Endocrinol Metab"},{"issue":"1","key":"2025012804210681400_luae254-B2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00439-020-02147-1","article-title":"Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease","volume":"140","author":"Cangiano","year":"2021","journal-title":"Hum Genet"},{"issue":"4","key":"2025012804210681400_luae254-B3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1297\/cpe.16.85","article-title":"Target height and target range for Japanese children: revisited","volume":"16","author":"Ogata","year":"2007","journal-title":"Clin Pediatr Endocrinol"},{"issue":"4","key":"2025012804210681400_luae254-B4","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s11102-007-0061-7","article-title":"Genetic insights into human isolated gonadotropin deficiency","volume":"10","author":"Trarbach","year":"2007","journal-title":"Pituitary"},{"issue":"10","key":"2025012804210681400_luae254-B5","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nrendo.2009.177","article-title":"The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism","volume":"5","author":"Bianco","year":"2009","journal-title":"Nat Rev Endocrinol"},{"issue":"5","key":"2025012804210681400_luae254-B6","first-page":"521","article-title":"Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations","volume":"19","author":"Seminara","year":"1998","journal-title":"Endocr Rev"},{"issue":"2","key":"2025012804210681400_luae254-B7","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1172\/JCI29884","article-title":"Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism","volume":"117","author":"Pitteloud","year":"2007","journal-title":"J Clin Invest"},{"key":"2025012804210681400_luae254-B8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000312693","article-title":"FGFR1 mutations in Kallmann syndrome","volume":"39","author":"Villanueva","year":"2010","journal-title":"Front Horm Res"},{"issue":"22","key":"2025012804210681400_luae254-B9","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJM199711273372205","article-title":"A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor","volume":"337","author":"de Roux","year":"1997","journal-title":"N Engl J Med"},{"issue":"34","key":"2025012804210681400_luae254-B10","doi-asserted-by":"crossref","first-page":"15140","DOI":"10.1073\/pnas.1009622107","article-title":"Oligogenic basis of isolated gonadotropin-releasing hormone deficiency","volume":"107","author":"Sykiotis","year":"2010","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/1\/luae254\/61440704\/luae254.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/1\/luae254\/61440704\/luae254.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T04:37:45Z","timestamp":1738039065000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luae254\/7954336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,12]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12,12]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luae254","relation":{},"ISSN":["2755-1520"],"issn-type":[{"type":"electronic","value":"2755-1520"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,12,12]]},"article-number":"luae254"}}