{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:29:57Z","timestamp":1789414197215,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA NS002824"],"award-info":[{"award-number":["ZIA NS002824"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of rare genetic disorders characterized by pubertal failure caused by gonadotropin\u2010releasing hormone (GnRH) deficiency. Genetic factors involved in semaphorin\/plexin signaling have been identified in patients with IHH. PlexinB1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D). In mice, perturbations in Sema4D\/PlexinB1 signaling leads to improper GnRH development, highlighting the importance of investigating PlexinB1 mutations in IHH families. In total, 336 IHH patients (normosmic IHH,\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a0293 and Kallmann syndrome,\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a043) from 290 independent families were included in the present study. Six\n                    <jats:italic>PLXNB1<\/jats:italic>\n                    rare sequence variants (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, and p.C1318R) are described in eight normosmic IHH patients from seven independent families. These variants were examined using bioinformatic modeling and compared to mutants reported in\n                    <jats:italic>PLXNA1<\/jats:italic>\n                    . Based on these analyses, the variant p.R1031H was assayed for alterations in cell morphology, PlexinB1 expression, and migration using a GnRH cell line and Boyden chambers. Experiments showed reduced membrane expression and impaired migration in cells expressing this variant compared to the wild\u2010type. Our results provide clinical, genetic, molecular\/cellular, and modeling evidence to implicate variants in\n                    <jats:italic>PLXNB1<\/jats:italic>\n                    in the etiology of IHH.\n                  <\/jats:p>","DOI":"10.1111\/jne.13103","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T15:44:11Z","timestamp":1643816651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<i>PLXNB1<\/i>\n                    mutations in the etiology of idiopathic hypogonadotropic hypogonadism"],"prefix":"10.1111","volume":"34","author":[{"given":"Bradley A.","family":"Welch","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomical Sciences University of Mississippi Medical Center  Jackson MS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010ju","family":"Cho","sequence":"additional","affiliation":[{"name":"Cellular and Developmental Neurobiology Section National Institute of Neurological Disorders and Stroke\/National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyit Ahmet","family":"Ucakturk","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Ankara Training and Research Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Matthew","family":"Farmer","sequence":"additional","affiliation":[{"name":"Cellular and Developmental Neurobiology Section National Institute of Neurological Disorders and Stroke\/National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semra","family":"Cetinkaya","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Dr. Sami Ulus Obstetrics and Gynecology Pediatric Health and Disease Training and Research Hospital University of Health Sciences  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayhan","family":"Abaci","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Faculty of Medicine Dokuz Eylul University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0976-159X","authenticated-orcid":false,"given":"Gamze","family":"Akkus","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Faculty of Medicine Cukurova University  Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enver","family":"Simsek","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Faculty of Medicine Eskisehir Osman Gazi University  Eskisehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6176-8986","authenticated-orcid":false,"given":"Leman Damla","family":"Kotan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Faculty of Medicine Cukurova University  Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan","family":"Turan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Faculty of Medicine Cukurova University  Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Gurbuz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Faculty of Medicine Cukurova University  Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilgin","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology Faculty of Medicine Cukurova University  Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-3915","authenticated-orcid":false,"given":"Susan","family":"Wray","sequence":"additional","affiliation":[{"name":"Cellular and Developmental Neurobiology Section National Institute of Neurological Disorders and Stroke\/National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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