{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:44:36Z","timestamp":1791931476569,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Selective deficiency of \u03b2\u2010subunit of luteinizing hormone (LHB) is a rare disease with scarce data on its characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To describe a male with LHB deficiency and systematically review the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Patients<\/jats:title><jats:p>Description of a male patient with LHB deficiency and a systematic review of LHB deficiency patients published to date (10 males and 3 females) as per PRISMA guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 36\u2010year\u2010old Asian Indian male presented with infertility. On evaluation, he had sexual maturity of Tanner's stage 3, low testosterone (0.23\u2009ng\/ml), low LH (0.44\u2009mIU\/ml), high follicle\u2010stimulating hormone (FSH, 22.4\u2009mIU\/ml), and a novel homozygous missense likely pathogenic variant (p.Cys46Arg) in <jats:italic>LHB<\/jats:italic>. In the molecular dynamics simulation study, this variant interferes with heterodimerization of alpha\u2010beta subunits. Eleven\u00a0males with pathogenic variants in <jats:italic>LHB<\/jats:italic> reported to date, presented at a median age of 29 (17\u201338) years, most commonly with delayed puberty. Clinical and biochemical profiles were similar to those of our patient. In the majority, testosterone monotherapy modestly increased testicular volume whereas human chorionic gonadotropin (hCG) monotherapy also improved spermatogenesis. In females, oligomenorrhoea after spontaneous menarche was the most common manifestation. Ten pathogenic\/likely pathogenic variants (three in\u2010frame deletions, three missense, two splice\u2010site, one nonsense, and one frameshift variants) have been reported in nine index patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report a novel likely pathogenic <jats:italic>LHB<\/jats:italic> variant in an Asian Indian patient. The typical phenotype in male patients with LHB deficiency is delayed puberty with low testosterone, low LH, and normal to high FSH and hCG monotherapy being the best therapeutic option.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14749","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T02:41:11Z","timestamp":1650940871000},"page":"383-393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Luteinizing hormone \u03b2\u2010subunit deficiency: Report of a novel <i>LHB<\/i> likely pathogenic variant and a systematic review of the published literature"],"prefix":"10.1111","volume":"98","author":[{"given":"Rohit","family":"Barnabas","sequence":"first","affiliation":[{"name":"Department of Endocrinology Seth G. S. Medical College &amp; KEM Hospital Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SwatiRamteke","family":"Jadhav","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Sapthagiri Institute of Medical Sciences and Research Center Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha","family":"Arya","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Seth G. S. Medical College &amp; KEM Hospital Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9623-4471","authenticated-orcid":false,"given":"Anurag Ranjan","family":"Lila","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Seth G. S. Medical College &amp; KEM Hospital Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya","family":"Sarathi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Vydehi Institute of Medical Sciences and Research Centre Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurang R.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Urology Saifee Hospital Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwambhar V.","family":"Bhandare","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering Indian Institute of Technology Bombay, Powai Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalini S.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Seth G. S. Medical College &amp; KEM Hospital Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8671-7816","authenticated-orcid":false,"given":"Ambarish","family":"Kunwar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering Indian Institute of Technology Bombay, Powai Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-4639","authenticated-orcid":false,"given":"Tushar","family":"Bandgar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Seth G. S. Medical College &amp; KEM Hospital Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2019.06.002"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199201163260306"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1986"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-924232"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-17-0749"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-1050"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-018-1133-5"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040326"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1584"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071999"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805792"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-16-0384"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2015.373"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02147-1"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-18907-1.00136-0"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.04.004"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000185497"},{"issue":"20","key":"e_1_2_14_19_1","first-page":"347","article-title":"Klinefelter syndrome: the commonest form of hypogonadism, but often overlooked or untreated","volume":"110","author":"Nieschlag E","year":"2013","journal-title":"Dtsch Arzteblatt Int"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03348174"},{"issue":"1","key":"e_1_2_14_21_1","first-page":"53","article-title":"Differential regulation of gonadotropin secretion by testosterone in the human male: absence of a negative feedback effect of testosterone on follicle\u2010stimulating hormone secretion","volume":"86","author":"Hayes FJ","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.83.6.4884"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32832029be"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-48-2-279"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1360235"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2004.06.069"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2015.00026"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.14749","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cen.14749","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.14749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T07:35:20Z","timestamp":1692430520000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.14749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,4]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/cen.14749"],"URL":"https:\/\/doi.org\/10.1111\/cen.14749","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,4]]},"assertion":[{"value":"2022-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}