{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:08:21Z","timestamp":1791198501268,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T00:00:00Z","timestamp":1415318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Turkish Scientific and Technical Research Council","award":["1095455"],"award-info":[{"award-number":["1095455"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The spectrum of genetic alterations in cases of hypogonadotropic hypogonadism continue to expand. However, <jats:italic><jats:styled-content style=\"fixed-case\">KISS<\/jats:styled-content>1R<\/jats:italic> mutations remain rare. The aim of this study was to understand the molecular basis of normosmic idiopathic hypogonadotropic hypogonadism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical characteristics, hormonal studies and genetic analyses of seven cases with idiopathic normosmic hypogonadotropic hypogonadism (<jats:styled-content style=\"fixed-case\">nIHH<\/jats:styled-content>) from three unrelated consanguineous families are presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One male presented with absence of pubertal onset and required surgery for severe penoscrotal hypospadias and cryptorchidism, while other two males had absence of pubertal onset. Two of four female cases required replacement therapy for pubertal onset and maintenance, whereas the other two had spontaneous pubertal onset but incomplete maturation. In sequence analysis, we identified a novel homozygous nonsense (p.Y323X) mutation (c.C969A) in the last exon of the <jats:italic><jats:styled-content style=\"fixed-case\">KISS<\/jats:styled-content>1R<\/jats:italic> gene in all clinically affected cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified a homozygous nonsense mutation in the <jats:italic><jats:styled-content style=\"fixed-case\">KISS1R<\/jats:styled-content><\/jats:italic> gene in three unrelated families with <jats:styled-content style=\"fixed-case\">nIHH<\/jats:styled-content>, which enabled us to observe the phenotypic consequences of this rare condition. Escape from nonsense\u2010mediated decay, and thus production of abnormal proteins, may account for the variable severity of the phenotype. Although <jats:italic><jats:styled-content style=\"fixed-case\">KISS1R<\/jats:styled-content><\/jats:italic> mutations are extremely rare and can cause a heterogeneous phenotype, analysis of the <jats:italic><jats:styled-content style=\"fixed-case\">KISS1R<\/jats:styled-content><\/jats:italic> gene should be a part of genetic analysis of patients with <jats:styled-content style=\"fixed-case\">nIHH<\/jats:styled-content>, to allow better understanding of phenotype\u2013genotype relationship of <jats:italic><jats:styled-content style=\"fixed-case\">KISS1R<\/jats:styled-content><\/jats:italic> mutations and the underlying genetic basis of patients with <jats:styled-content style=\"fixed-case\">nIHH<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12618","type":"journal-article","created":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T03:13:10Z","timestamp":1411787590000},"page":"429-438","source":"Crossref","is-referenced-by-count":21,"title":["Normosmic idiopathic hypogonadotropic hypogonadism due to a novel homozygous nonsense c.C969A (p.Y323X) mutation in the <i><scp>KISS<\/scp>1R<\/i> gene in three unrelated families"],"prefix":"10.1111","volume":"82","author":[{"given":"Huseyin","family":"Demirbilek","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology Children's State Hospital Diyarbakir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Nuri","family":"Ozbek","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Children's State Hospital Diyarbakir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korcan","family":"Demir","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Children's Hospital Gaziantep Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Damla","family":"Kotan","sequence":"additional","affiliation":[{"name":"Institute of Sciences Department of Biotechnology Cukurova University Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasar","family":"Cesur","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Yuzuncu Yil University Van Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Dogan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Yuzuncu Yil University Van Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Temiz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Division of Pediatric Endocrinology Cukurova University Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eda","family":"Mengen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Division of Pediatric Endocrinology Cukurova University Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Gurbuz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Division of Pediatric Endocrinology Cukurova University Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilgin","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Division of Pediatric Endocrinology Cukurova University Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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