{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:27:56Z","timestamp":1771464476707,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,11,20]],"date-time":"2006-11-20T00:00:00Z","timestamp":1163980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> The pathogenesis of idiopathic hypogonadotrophic hypogonadism (IHH) is mostly unclear. We characterized the clinical findings and molecular analysis of <jats:italic>GnRHR<\/jats:italic> and <jats:italic>KAL1<\/jats:italic> genes in 26 Brazilian males with IHH with and without hyposmia\/anosmia.<\/jats:p><jats:p><jats:bold>Design\u2002<\/jats:bold> Clinical assessment was performed for endocrine status, olfactory structure and function, renal lesion, and mirror movement. The diagnosis of Kallmann syndrome (KS) included HH and the clinical complaint of hyposmia\/anosmia or decreased olfactory acuity obtained by the Smell Identification Test\u2122 (SIT). We analysed <jats:italic>GnRHR<\/jats:italic> and <jats:italic>KAL1<\/jats:italic> genes using the polymerase chain reaction (PCR) direct sequencing method.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> A variable degree of HH was observed, including various clinical abnormalities, such as cryptorchidism, hearing loss, strabismus, cleft lip\/palate, high\u2010arched palate, dental agenesis, psychiatric disorders, learning dysfunction, and bimanual synkinesia. Twenty\u2010two out of 26 patients with IHH (85%) were classified as KS. Abnormalities of olfactory bulbs\/sulci were observed in 79% of KS patients. One\u2010third of KS patients had renal defects and 45\u00b75% had a positive family history. <jats:italic>GnRHR<\/jats:italic> gene sequence analysis showed no mutations. <jats:italic>KAL1<\/jats:italic> sequence analysis identified two novel missense mutations: c.1061A to G in exon\u00a07 (N304S) and c.1583C to A in exon 10 (S478X). We also observed a 14\u2010bp deletion within exon\u00a011 that caused a premature termination. According to the National Center for Biotechnology Information (NCBI)\u2010Single Nucleotide Polymorphism (SNP) database, two previously described polymorphisms (rs808119 and rs809446) were detected.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold>  <jats:italic>KAL1<\/jats:italic> mutations accounted for 12% of KS patients. This low prevalence of <jats:italic>KAL1<\/jats:italic> mutations indicates that other genes, such as the fibroblast growth factor receptor\u00a01 (<jats:italic>FGFR1<\/jats:italic>) gene or other as yet undiscovered genes, epigenetic events and\/or environmental factors might be involved in the aetiology and phenotypic variability of KS.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2006.02702.x","type":"journal-article","created":{"date-parts":[[2006,11,20]],"date-time":"2006-11-20T09:25:26Z","timestamp":1164014726000},"page":"173-179","source":"Crossref","is-referenced-by-count":21,"title":["Clinical assessment and molecular analysis of <i>GnRHR<\/i> and <i>KAL1<\/i> genes in males with idiopathic hypogonadotrophic hypogonadism"],"prefix":"10.1111","volume":"66","author":[{"given":"Beatriz R.","family":"Versiani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ericka","family":"Trarbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Koenigkam\u2010Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Carlos","family":"Dos Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucila L. 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