{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T07:50:32Z","timestamp":1768290632219,"version":"3.49.0"},"reference-count":50,"publisher":"Walter de Gruyter GmbH","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background:<\/jats:title><jats:p>Congenital hypogonadotropic hypogonadism (CHH) is classified as Kallmann syndrome (KS) with anosmia\/hyposmia or normosmic (n)CHH. Here, we investigated the genetic causes and phenotype-genotype correlations in Japanese patients with CHH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>We enrolled 22 Japanese patients with CHH from 21 families (18 patients with KS and 4 with nCHH) and analyzed 27 genes implicated in CHH by next-generation and Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>We detected 12 potentially pathogenic mutations in 11 families, with three having a mutation in<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>The frequency of CHH genes in the Japanese was compatible with previous reports, except that<\/jats:p><\/jats:sec>","DOI":"10.1515\/jpem-2017-0035","type":"journal-article","created":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T10:01:57Z","timestamp":1505469717000},"source":"Crossref","is-referenced-by-count":19,"title":["Molecular genetic and clinical delineation of 22 patients with congenital hypogonadotropic hypogonadism"],"prefix":"10.1515","volume":"30","author":[{"given":"Kohei","family":"Aoyama","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruo","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsushi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Togawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Negishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikumi","family":"Hori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Izawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Hamajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Saitoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","reference":[{"key":"ref171","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s100380070033","article-title":"A novel interstitial deletion of KAL1 in a Japanese family with Kallmann syndrome","volume":"45","year":"2000","journal-title":"J Hum Genet"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s100380070033","article-title":"A novel interstitial deletion of KAL1 in a Japanese family with Kallmann syndrome","volume":"45","year":"2000","journal-title":"J Hum Genet"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"15140","DOI":"10.1073\/pnas.1009622107","article-title":"Oligogenic basis of isolated gonadotropin-releasing hormone deficiency","volume":"107","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"E2138","DOI":"10.1210\/jc.2014-2110","article-title":"The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients","volume":"99","year":"2014","journal-title":"J Clin Endocrinol 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genes encoding prokineticin-2 and prokineticin receptor-2","volume":"2","year":"2006","journal-title":"PLoS Genet"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1530\/eje.1.02342","article-title":"Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review","volume":"156","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"E858","DOI":"10.1210\/jc.2011-2652","article-title":"The results of CHD7 analysis in clinically well-characterized patients with Kallmann syndrome","volume":"97","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1210\/jc.2009-2320","article-title":"TAC3\/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood","volume":"95","year":"2010","journal-title":"J Clin 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activity","volume":"18","year":"2009","journal-title":"Hum Mol Genet"},{"key":"ref401","first-page":"43","article-title":"Dental findings associated with the malformations of CHARGE","volume":"24","year":"2002","journal-title":"Pediatr Dent"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/humu.9298","article-title":"Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2)","volume":"25","year":"2005","journal-title":"Hum Mutat"},{"key":"ref151","first-page":"43","article-title":"Dental findings associated with the malformations of CHARGE","volume":"24","year":"2002","journal-title":"Pediatr Dent"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.ajhg.2010.08.018","article-title":"WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome","volume":"87","year":"2010","journal-title":"Am J Hum 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Genet"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ajhg.2013.03.024","article-title":"Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness","volume":"92","year":"2013","journal-title":"Am J Hum Genet"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","year":"2015","journal-title":"Genet Med"},{"key":"ref111","first-page":"649698","article-title":"Novel FGFR1 and KISS1R mutations in Chinese Kallmann syndrome males with cleft lip\/palate","volume":"2015","year":"2015","journal-title":"BioMed Res Int"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1530\/eje.1.02342","article-title":"Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review","volume":"156","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ajhg.2013.03.024","article-title":"Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness","volume":"92","year":"2013","journal-title":"Am J Hum Genet"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1111\/cen.13231","article-title":"Reversal of congenital hypogonadotropic hypogonadism in a man with Kallmann syndrome due to SOX10 mutation","volume":"85","year":"2016","journal-title":"Clin Endocrinol"},{"key":"ref491","doi-asserted-by":"crossref","first-page":"15140","DOI":"10.1073\/pnas.1009622107","article-title":"Oligogenic basis of isolated gonadotropin-releasing hormone deficiency","volume":"107","year":"2010","journal-title":"Proc Natl Acad Sci 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