{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:12:49Z","timestamp":1783555969407,"version":"3.55.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1995,3,14]]},"abstract":"Genomic DNA from 32 unrelated families with male-limited precocious puberty was examined for the previously described Asp-578-->Gly, Met-571-->Ile, and Thr-577-->Ile mutations in transmembrane helix 6 of the human luteinizing hormone receptor (hLHR). Twenty-eight families had the inherited form of the disorder, and of these, 24 were found to have the Asp-578-->Gly mutation. Four additional mutations were found among the remaining four families with the inherited form and in four sporadic cases of the disorder: an A-->C transversion resulting in substitution of leucine for Ile-542 in the fifth transmembrane helix, an A-->G transition resulting in substitution of glycine for Asp-564 in the third cytoplasmic loop, a G-->T transversion resulting in substitution of tyrosine for Asp-578 in the sixth transmembrane helix, and a T-->C transition resulting in substitution of arginine for Cys-581 in the sixth transmembrane helix. Human embryonic kidney cells transfected with cDNAs for each of the mutant hLHRs, created by PCR-based mutagenesis of the wild-type hLHR cDNA, exhibited increased levels of basal cAMP production in the absence of agonist, indicating constitutive activation of the mutation hLHRs. Three of the additional mutations had specific features: Ile-542-->Leu and Cys-581-->Arg appeared ligand-unresponsive, whereas Asp-578-->Tyr appeared to correlate genotype with phenotype. We conclude that the region spanning nt 1624-1741 of exon 11 is a hotspot for heterogeneous point mutations that constitutively activate the hLHR and cause male-limited precocious puberty.<\/jats:p>","DOI":"10.1073\/pnas.92.6.1906","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:29:22Z","timestamp":1149067762000},"page":"1906-1910","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":189,"title":["Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty."],"prefix":"10.1073","volume":"92","author":[{"given":"L","family":"Laue","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Y","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S Y","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Blomberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"G B","family":"Cutler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Georgetown University Medical Center, Washington, D.C. 20007."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1995,3,14]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.92.6.1906","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:06:33Z","timestamp":1649858793000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.92.6.1906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,3,14]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1995,3,14]]}},"alternative-id":["10.1073\/pnas.92.6.1906"],"URL":"https:\/\/doi.org\/10.1073\/pnas.92.6.1906","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,3,14]]},"assertion":[{"value":"1995-03-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}