{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T11:35:00Z","timestamp":1772537700328,"version":"3.50.1"},"reference-count":0,"publisher":"Bioscientifica","issue":"6","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare disorder characterised by lack of pubertal development and infertility, due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH) and, unlike Kallmann syndrome, is associated with a normal sense of smell. Mutations in the <jats:italic>GNRHR<\/jats:italic> gene cause autosomal recessive nCHH. The aim of this study was to determine the prevalence of <jats:italic>GNRHR<\/jats:italic> mutations in a group of 40 patients with nCHH.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Cross-sectional study of 40 unrelated patients with nCHH.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients were screened for mutations in the <jats:italic>GNRHR<\/jats:italic> gene by DNA sequencing.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p><jats:italic>GNRHR<\/jats:italic> mutations were identified in five of 40 patients studied. Four patients had biallelic mutations (including a novel frameshift deletion p.Phe313Metfs*3, in two families) in agreement with autosomal recessive inheritance. One patient had a heterozygous <jats:italic>GNRHR<\/jats:italic> mutation associated with a heterozygous <jats:italic>PROKR2<\/jats:italic> mutation, thus suggesting a possible role of synergistic heterozygosity in the pathogenesis of the disorder.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This study further expands the spectrum of known genetic defects associated with nCHH. Although <jats:italic>GNRHR<\/jats:italic> mutations are usually biallelic and inherited in an autosomal recessive manner, the presence of a monoallelic mutation in a patient should raise the possibility of a digenic\/oligogenic cause of nCHH.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/ec-17-0104","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T00:30:24Z","timestamp":1497400224000},"page":"360-366","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":18,"title":["GNRHR biallelic and digenic mutations in patients with normosmic congenital hypogonadotropic hypogonadism"],"prefix":"10.1530","volume":"6","author":[{"given":"Catarina I","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"1CICS-UBIHealth Sciences Research Centre, University of Beira Interior, Covilh\u00e3, Portugal"}]},{"given":"Jos\u00e9 M","family":"Arag\u00fc\u00e9s","sequence":"additional","affiliation":[{"name":"2Servi\u00e7o de EndocrinologiaDiabetes e Metabolismo, Hospital de Santa Maria, Lisboa, Portugal"}]},{"given":"Margarida","family":"Bastos","sequence":"additional","affiliation":[{"name":"3Servi\u00e7o de EndocrinologiaDiabetes e Metabolismo, Centro Hospitalar Universit\u00e1rio de Coimbra, Coimbra, Portugal"}]},{"given":"Lu\u00edsa","family":"Barros","sequence":"additional","affiliation":[{"name":"3Servi\u00e7o de EndocrinologiaDiabetes e Metabolismo, Centro Hospitalar Universit\u00e1rio de Coimbra, Coimbra, Portugal"}]},{"given":"Nuno","family":"Vicente","sequence":"additional","affiliation":[{"name":"3Servi\u00e7o de EndocrinologiaDiabetes e Metabolismo, Centro Hospitalar Universit\u00e1rio de Coimbra, Coimbra, Portugal"}]},{"given":"Davide","family":"Carvalho","sequence":"additional","affiliation":[{"name":"4Servi\u00e7o de EndocrinologiaDiabetes e Metabolismo, Hospital de S\u00e3o Jo\u00e3o e Faculdade de Medicina do Porto, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto, Porto, Portugal"}]},{"given":"Manuel C","family":"Lemos","sequence":"additional","affiliation":[{"name":"1CICS-UBIHealth Sciences Research Centre, University of Beira Interior, Covilh\u00e3, Portugal"}]}],"member":"416","container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/6\/6\/360.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/6\/6\/360.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T17:30:43Z","timestamp":1608658243000},"score":1,"resource":{"primary":{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/6\/6\/360.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8]]},"references-count":0,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/ec-17-0104","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8]]}}}