{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:40:22Z","timestamp":1783478422260,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971375"],"award-info":[{"award-number":["81971375"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771576"],"award-info":[{"award-number":["81771576"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC0905100"],"award-info":[{"award-number":["2016YFC0905100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to analyse <jats:italic>FGFR1<\/jats:italic> rare variants in a series of Chinese congenital hypogonadotropic hypogonadism (CHH) patients. In addition, we intended to understand the clinical characteristics and the response to treatment of CHH patients with <jats:italic>FGFR1<\/jats:italic> rare variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>A total of 357 CHH patients were recruited at Peking Union Medical College Hospital. We used Sanger sequencing to analyse <jats:italic>FGFR1<\/jats:italic> gene. In silico analysis was carried out to study the pathogenicity of novel missense variants. The clinical, endocrinological and therapeutic effects from patients carrying <jats:italic>FGFR1<\/jats:italic> rare variants were analysed retrospectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thimissense mutations.rty patients in this series were found to harbour 29 <jats:italic>FGFR1<\/jats:italic> rare variants, with 8 recurrent and 21 novel variants. After comprehensive analysis, 18 out of 21 novel variants were classified as likely pathogenic (LP) ones. These variants are widely spread throughout the <jats:italic>FGFR1<\/jats:italic> gene and almost all FGFR1 functional domains, which exhibited no hot spot. Cryptorchidism, cleft palate and dental abnormality incidence in this CHH series that possessed <jats:italic>FGFR1<\/jats:italic> LP variants were approximately 38.5%, 7.6% and 3.8%, respectively. Among patients who accepted the fertility\u2010promoting treatment, 8 out of 10 patients succeeded in spermatogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Eighteen novel LP variants were found to expand the spectrum of <jats:italic>FGFR1<\/jats:italic> rare variants. In CHH patients possessing <jats:italic>FGFR1<\/jats:italic> variants, we found that the rate of spermatogenesis was high following fertility\u2010promoting therapy and the existence of cryptorchidism may represent the underlying factors which affect spermatogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14436","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T17:02:54Z","timestamp":1612630974000},"page":"153-162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel rare variants in <i>FGFR1<\/i> and clinical characteristics analysis in a series of congenital hypogonadotropic hypogonadism patients"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-0044","authenticated-orcid":false,"given":"Min","family":"Nie","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital) 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