{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T09:52:46Z","timestamp":1777197166602,"version":"3.51.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:p>Testosterone production by the fetal testis depends on a functional relationship between hCG and the LH\/chorionic gonadotropin receptor (LHCGR). Failure of the receptor to correctly respond to its ligand leads to impaired sexual differentiation in males. A phenotypically female patient with pubertal delay had a 46,XY karyotype and was diagnosed with 46,XY disorder of sex development (DSD). Novel compound heterozygous <jats:italic>LHCGR<\/jats:italic> mutations were found in the signal peptide: a duplication p.L10_Q17dup of maternal origin, and a deletion (p.K12_L15del) and a p.L16Q missense mutation of paternal origin. cAMP production was very low for both the deletion and duplication mutations and was halved for the missense mutant. The duplication and missense mutations were both expressed intracellularly, but at very low levels at the cell membrane; they were most likely retained in the endoplasmic reticulum. The deletion mutant had a very limited intracellular expression, indicating impaired biosynthesis. There was reduced expression of all three mutants, which was most marked for the deletion mutation. There was also decreased protein expression of all three mutant receptors. In the deletion mutation, the presence of a lower-molecular-weight band corresponding to LHCGR monomer, probably due to lack of glycosylation, and a lack of bands corresponding to dimers\/oligomers suggests absent ER entry. This novel case of 46,XY DSD illustrates how different LHCGR signal peptide mutations led to complete receptor inactivation by separate mechanisms. The study underlines the importance of specific regions of signal peptides and expands the spectrum of <jats:italic>LHCGR<\/jats:italic> mutations.<\/jats:p>","DOI":"10.1530\/eje-19-0170","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T15:00:20Z","timestamp":1559746820000},"page":"K11-K20","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":8,"title":["Compound heterozygous mutations in the luteinizing hormone receptor signal peptide causing 46,XY disorder of sex development"],"prefix":"10.1093","volume":"181","author":[{"given":"Iulia","family":"Potorac","sequence":"first","affiliation":[{"name":"1Department of Endocrinology, Centre Hospitalier Universitaire de Li\u00e8ge, Universit\u00e9 de Li\u00e8ge, Domaine Universitaire du Sart-Tilman, Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashutosh","family":"Trehan","sequence":"additional","affiliation":[{"name":"2Institute of Biomedicine, University of Turku, Turku, Finland"},{"name":"3MRC Laboratory of Molecular Biology, Protein and Nucleic Acid Chemistry Division, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamila","family":"Szyma\u0144ska","sequence":"additional","affiliation":[{"name":"4Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Fudvoye","sequence":"additional","affiliation":[{"name":"5Department of Pediatrics, Centre Hospitalier Universitaire de Li\u00e8ge, Universit\u00e9 de Li\u00e8ge, Domaine Universitaire du Sart-Tilman, Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Thiry","sequence":"additional","affiliation":[{"name":"6Department of Anatomopathology, Centre Hospitalier Universitaire de Li\u00e8ge, Universit\u00e9 de Li\u00e8ge, Domaine Universitaire du Sart-Tilman, Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilpo","family":"Huhtaniemi","sequence":"additional","affiliation":[{"name":"2Institute of Biomedicine, University of Turku, Turku, Finland"},{"name":"7Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Hammersmith Campus, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian F","family":"Daly","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, Centre Hospitalier Universitaire de Li\u00e8ge, Universit\u00e9 de Li\u00e8ge, Domaine Universitaire du Sart-Tilman, Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Beckers","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, Centre Hospitalier Universitaire de Li\u00e8ge, Universit\u00e9 de Li\u00e8ge, Domaine Universitaire du Sart-Tilman, Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Simone","family":"Parent","sequence":"additional","affiliation":[{"name":"5Department of Pediatrics, Centre Hospitalier Universitaire de Li\u00e8ge, Universit\u00e9 de Li\u00e8ge, Domaine Universitaire du Sart-Tilman, Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adolfo","family":"Rivero-M\u00fcller","sequence":"additional","affiliation":[{"name":"2Institute of Biomedicine, University of Turku, Turku, Finland"},{"name":"4Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland"},{"name":"8Faculty of Natural Sciences and Technology, \u00c5bo Akademi University, Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/181\/2\/EJE-19-0170.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/181\/2\/EJE-19-0170.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:13:18Z","timestamp":1676391198000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/181\/2\/K11\/6654113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/eje-19-0170","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8]]}}}