{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:40Z","timestamp":1787014000520,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,9,13]],"date-time":"2017-09-13T00:00:00Z","timestamp":1505260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"crossref","award":["2016YFC0901505"],"award-info":[{"award-number":["2016YFC0901505"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing Municipal Science and Technology Funding","award":["Z151100003915103"],"award-info":[{"award-number":["Z151100003915103"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"Summary<\/jats:title>\n \n Context<\/jats:title>\n \n The diagnosis of congenital hypogonadotropic hypogonadism (\n CHH<\/jats:styled-content>\n ) in prepuberty has always been challenging. Here, we aimed at studying the clinical and genetic features of paediatric\n CHH<\/jats:styled-content>\n , especially the phenotype of hypospadias and dual defects (patients showing hypothalamic and\/or pituitary defects and testicular hypoplasia), so as to have a better understanding of\n CHH<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n \n The clinical and genetic features of patients with\n CHH<\/jats:styled-content>\n were analysed, and the relationships between hypospadias, dual defects and genetics were investigated.\n <\/jats:p>\n <\/jats:sec>\n \n Patients<\/jats:title>\n \n Patients who visited Beijing Children's Hospital and were positively diagnosed with\n CHH<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Measurements<\/jats:title>\n \n The collected data included sex hormones,\n MRI<\/jats:styled-content>\n of the olfactory bulb, human chorionic gonadotrophin (\n hCG<\/jats:styled-content>\n ) test and genetic testing. We analysed clinical features and genetic results, especially hypospadias and dual defects, and compared the stimulated testosterone (T) levels in patients with and without cryptorchidism.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Sixty\u2010four patients were positively diagnosed, and forty\u2010seven (73.4%) had Kallmann syndrome (\n KS<\/jats:styled-content>\n ). Four patients (6.3%) had hypospadias, including 2\n KS<\/jats:styled-content>\n . Micropenis combined with cryptorchidism was the most common phenotype (39%). Approximately two\u2010third of patients showed a poor response to\n hCG<\/jats:styled-content>\n ; 15 cases were diagnosed with dual defects, and there were no significant differences between those with and without cryptorchidism. Twenty\u2010six cases (51%) of 51 patients were identified as having classical\n HH<\/jats:styled-content>\n mutations, affecting 10 different genes, with oligogenic mutations in 5 cases (9.8%). The most common mutations were in\n \n PROKR<\/jats:styled-content>\n 2\n <\/jats:italic>\n (17.6%),\n \n FGFR<\/jats:styled-content>\n 1\n <\/jats:italic>\n (13.7%) and\n CHD<\/jats:styled-content>\n 7 (7.8%). The frequency of\n \n PROKR<\/jats:styled-content>\n 2\n <\/jats:italic>\n mutations was higher in dual\n HH<\/jats:styled-content>\n when compared to other\n HH<\/jats:styled-content>\n cases (6\/15 vs 3\/36,\n P<\/jats:italic>\n \u00a0=\u00a0.021).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Micropenis and\/or cryptorchidism can serve as important signs for the diagnosis of\n HH<\/jats:styled-content>\n in paediatrics, and the coexistence of hypospadias does not exclude the diagnosis of\n CHH<\/jats:styled-content>\n , including\n KS<\/jats:styled-content>\n or normosmic isolated\n HH<\/jats:styled-content>\n (nHH). Testicular function may be impaired earlier than expected, and\n \n PROKR<\/jats:styled-content>\n 2\n <\/jats:italic>\n mutations need to be evaluated to identify presumed dual defects.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cen.13451","type":"journal-article","created":{"date-parts":[[2017,8,20]],"date-time":"2017-08-20T07:16:36Z","timestamp":1503213396000},"page":"757-766","source":"Crossref","is-referenced-by-count":43,"title":["Clinical and genetic features of 64 young male paediatric patients with congenital hypogonadotropic hypogonadism"],"prefix":"10.1111","volume":"87","author":[{"given":"Yi","family":"Wang","sequence":"first","affiliation":[{"name":"National Center for Children's Health Capital Medical University Beijing China"},{"name":"Department of Endocrinology, Genetics, Metabolism and Adolescent Medicine Beijing Children's Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory for Genetics of Birth Defects Beijing Children's Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1262-7383","authenticated-orcid":false,"given":"Chunxiu","family":"Gong","sequence":"additional","affiliation":[{"name":"National Center for Children's Health Capital Medical University Beijing China"},{"name":"Department of Endocrinology, Genetics, Metabolism and Adolescent Medicine Beijing Children's Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory for Genetics of Birth Defects Beijing Children's Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Qin","sequence":"additional","affiliation":[{"name":"National Center for Children's Health Capital Medical University Beijing China"},{"name":"Department of Endocrinology, Genetics, Metabolism and Adolescent Medicine Beijing Children's Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory for Genetics of Birth Defects Beijing Children's Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"National Center for Children's Health Capital Medical University Beijing China"},{"name":"Department of Pharmacy Beijing Children's Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Tian","sequence":"additional","affiliation":[{"name":"National Center for Children's Health Capital Medical University Beijing China"},{"name":"Department of Endocrinology, Genetics, Metabolism and Adolescent Medicine Beijing Children's Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory for Genetics of Birth Defects Beijing Children's Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.177"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2001.01277.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.112"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.08.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00051"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2582"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077827"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12996"},{"key":"e_1_2_7_10_1","first-page":"942","article-title":"Children with idiopathic hypogonadotropic hypogonadism clinical data analysis and mutations analysis of KAL1 and FGFR1 gene","volume":"52","author":"Qin MGC","year":"2014","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201777"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000441988"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.05.061"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1122"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34538"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.008"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-017-0098-2"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1105-y"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0912"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-60-2-333"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-7-1-11"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1664"},{"key":"e_1_2_7_23_1","first-page":"704","article-title":"Expanding the genetic spectrum of ANOS1 mutations in patients with congenital hypogonadotropic hypogonadism","volume":"32","author":"Gon\u00e7alves CI","year":"2017","journal-title":"Hum Reprod"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00109"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009622107"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201232"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2047-2927.2012.00008.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335160"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508881103"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.13451","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.13451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T02:13:11Z","timestamp":1695521591000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.13451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,13]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1111\/cen.13451"],"URL":"https:\/\/doi.org\/10.1111\/cen.13451","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,13]]}}}