{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:33:18Z","timestamp":1787243598143,"version":"build-2736575974"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"name":"Basic Science Research Program through the National Research\nFoundation of Korea (NRF) funded by the Ministry of\nEducation","award":["2017R1D1A1B03029638"],"award-info":[{"award-number":["2017R1D1A1B03029638"]}]},{"name":"Asan Medical Center Children's Hospital, Seoul,\nKorea.","award":["2019-481"],"award-info":[{"award-number":["2019-481"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background Isolated gonadotropin-releasing hormone (GnRH) deficiency\n(IGD) has a wide phenotypic spectrum including Kallmann syndrome (KS) and\nnormosmic idiopathic hypogonadotropic hypogonadism (nIHH). FGFR1\nmutations have been identified in 3\u201310% of patients with KS or\nnIHH. This study was performed to investigate clinical phenotypes and functional\ncharacteristics of FGFR1 mutations in patients with IGD.<\/jats:p>\n                  <jats:p>Methods This study included 8 patients (from 7 families) with\nFGFR1 mutations identified by targeted gene panel sequencing or whole\nexome sequencing (WES). The impact of the identified mutations on FGFR1 function\nwas assessed using in vitro studies.<\/jats:p>\n                  <jats:p>Results Seven heterozygous mutations in FGFR1 were identified in 8\npatients from 7 independent families. The patients exhibited a wide spectrum of\npubertal development, including anosmia in a prepubertal boy (n=1),\ndelayed puberty (n=2), nIHH (n=3), and KS (n=2). Four of\nthe mutations were classified as likely pathogenic, and the other three were\nvariants of uncertain significance. FGF8-FGFR1 signaling activities for the\nnovel FGFR1 variants (p.Y339H, p.S681I, and p.N185Kfs*16) were reduced\nby in vitro functional assay, indicating loss-of-function mutations.<\/jats:p>\n                  <jats:p>Conclusions This study identified seven rare sequence variants in\nFGFR1 in patients with KS and nIHH. Probands with an FGFR1\nmutations displayed a wide phenotypic spectrum ranging from KS to anosmia. A\nprepubertal male with anosmia should be followed up to assess pubertal\ndevelopment because they can manifest hypogonadotropic hypogonadism after\npuberty. These results expand the phenotypic spectrum of FGFR1 mutations\nand suggest a broader biologic role of FGFR1 in reproduction.<\/jats:p>","DOI":"10.1055\/a-1151-4800","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T18:53:06Z","timestamp":1591123986000},"page":"457-463","source":"Crossref","is-referenced-by-count":5,"title":["Functional Characteristics of Novel FGFR1 Mutations in Patients with Isolated Gonadotropin-Releasing Hormone Deficiency"],"prefix":"10.1055","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1196-7826","authenticated-orcid":false,"given":"Jin-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Asan Medical Center Children\u2019s\nHospital, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arum","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Asan Medical Center Children\u2019s\nHospital, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yena","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Asan Medical Center Children\u2019s\nHospital, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu-Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Genetics Center, Asan Medical Center, University of Ulsan\nCollege of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Wook","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Asan Medical Center Children\u2019s\nHospital, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1210\/edrv-7-1-11","article-title":"Hypogonadotropic disorders in men and women: diagnosis and therapy with\npulsatile gonadotropin-releasing hormone","volume":"7","author":"N Santoro","year":"1986","journal-title":"Endocr Rev"},{"key":"ref2","first-page":"521","article-title":"Gonadotropin-releasing hormone deficiency in the human (idiopathic\nhypogonadotropic hypogonadism and Kallmann's syndrome):\npathophysiological and genetic considerations","volume":"19","author":"S B Seminara","year":"1998","journal-title":"Endocr Rev"},{"key":"ref3","first-page":"113","article-title":"Update on the genetics of idiopathic hypogonadotropic hypogonadism","volume":"9","author":"A K Topaloglu","year":"2017","journal-title":"J Clin Res Pediatr 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Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1151-4800.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T18:45:35Z","timestamp":1622486735000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1151-4800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,2]]},"references-count":37,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2021,5,31]]},"published-print":{"date-parts":[[2021,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1151-4800","relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,2]]}}}