{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:30:00Z","timestamp":1791599400297,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,10,16]],"date-time":"2014-10-16T00:00:00Z","timestamp":1413417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["477016\/2011-1"],"award-info":[{"award-number":["477016\/2011-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:p>RFamide\u2010related peptide\u20103 (RFRP\u20103), the orthologue of avian gonadotrophin\u2010inhibitory hormone, and its receptor GPR147 have been recently identified in the human hypothalamus, and their roles in the regulation of reproductive axis has been studied. The present study aimed to investigate whether the presence of variants in the genes encoding human RFRP\u20103 (<jats:italic>NPVF<\/jats:italic> gene) and its receptor, GPR147 (<jats:italic>NPFFR1<\/jats:italic> gene), is associated with the occurrence of gonadotrophin\u2010releasing hormone\u2010dependent pubertal disorders. Seventy\u2010eight patients with idiopathic central precocious puberty (CPP) and 51 with normosmic isolated hypogonadotrophic hypogonadism (<jats:styled-content style=\"fixed-case\">nIHH<\/jats:styled-content>) were investigated. Fifty healthy subjects comprised the control group. The coding sequences of the <jats:italic>NPVF<\/jats:italic> and <jats:italic>NPFFR1<\/jats:italic> genes were amplified and sequenced. Odds ratios (OR) were used to estimate the likelihood of CPP or nIHH in the presence of the described polymorphisms. All such polymorphisms have already been registered in the National Center for Biotechnology Information database. A three\u2010nucleotide in frame deletion was identified in the <jats:italic>NPVF<\/jats:italic> gene (p.I71_K72), with a smaller proportion in the CPP (5%) compared to the <jats:styled-content style=\"fixed-case\">nIHH<\/jats:styled-content> (15%) group (P\u00a0=\u00a00.06). This results in the deletion of the isoleucine at position 71, adjacent to lysine at an endoproteolytic cleavage site of the precursor peptide. This polymorphism was associated with a lower risk of CPP (OR\u00a0=\u00a00.33; 95% confidence interval\u00a0=\u00a00.08\u20130.88); interestingly, only two men with <jats:styled-content style=\"fixed-case\">nIHH<\/jats:styled-content> were homozygotes for this variant. A total of five missense polymorphisms were found in the <jats:italic>NPFFR1<\/jats:italic> gene, which encodes GPR147, with similar frequencies among groups and no association with pubertal timing. Our data suggest that RFRP\u20103\/GPR147 may play secondary, modulatory roles on the regulation of pubertal development; a restraining modulatory effect of the NPVF p.I71_K72 variant on the activation of the gonadotrophic axis cannot be ruled out and deserves further investigation.<\/jats:p>","DOI":"10.1111\/jne.12207","type":"journal-article","created":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T11:42:32Z","timestamp":1409658152000},"page":"817-824","source":"Crossref","is-referenced-by-count":21,"title":["Mutational Analysis of the Genes Encoding RFAmide\u2010Related Peptide\u20103, the Human Orthologue of Gonadotrophin\u2010Inhibitory Hormone, and its Receptor (<scp>GPR<\/scp>147) in Patients with Gonadotrophin\u2010Releasing Hormone\u2010Dependent Pubertal Disorders"],"prefix":"10.1111","volume":"26","author":[{"given":"C. J. 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