{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:53:30Z","timestamp":1793199210753,"version":"4.5.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"50","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,12,16]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Inactivating mutations in the chromodomain helicase DNA binding protein 7 (\n                    <jats:italic>CHD7<\/jats:italic>\n                    ) gene causes a severe developmental disorder known as CHARGE syndrome. Recently, several missense mutations in\n                    <jats:italic>CHD7<\/jats:italic>\n                    have been reported in isolated gonadotropin-releasing hormone (GnRH) -deficiency (IGD) patients who lack full CHARGE features. However, the precise functional consequence of these IGD-associated missense mutations on the activity of CHD7 protein is not known. This study confirms the predominance of missense\n                    <jats:italic>CHD7<\/jats:italic>\n                    alleles in 5% of IGD patients and provides, to our knowledge, first experimental evidence that functionally compromised\n                    <jats:italic>CHD7<\/jats:italic>\n                    missense alleles contribute to the pathogenesis of both the anosmic and normosmic forms of IGD. These results imply a preferential sensitivity for\n                    <jats:italic>CHD7<\/jats:italic>\n                    dysfunction in the developmental ontogeny as well as neuroendocrine regulation of GnRH neurons in humans.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1417438111","type":"journal-article","created":{"date-parts":[[2014,12,3]],"date-time":"2014-12-03T22:54:05Z","timestamp":1417647245000},"page":"17953-17958","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":73,"title":["Functionally compromised\n                    <i>CHD7<\/i>\n                    alleles in patients with isolated GnRH deficiency"],"prefix":"10.1073","volume":"111","author":[{"given":"Ravikumar","family":"Balasubramanian","sequence":"first","affiliation":[{"name":"Harvard Reproductive Endocrine Sciences Center &amp; Reproductive Endocrine Unit of the Department of Medicine, and"},{"name":"Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Harvard Reproductive Endocrine Sciences Center &amp; Reproductive Endocrine Unit of the Department of Medicine, and"},{"name":"Department of Pediatrics, Asan Medical Center Children\u2019s Hospital, University of Ulsan College of Medicine, Seoul 138-736, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Francescatto","sequence":"additional","affiliation":[{"name":"Center for Human Disease Modeling, Department of Cell Biology and Pediatrics, Duke University, Durham, NC 27710;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Willer","sequence":"additional","affiliation":[{"name":"Center for Human Disease Modeling, Department of Cell Biology and Pediatrics, Duke University, Durham, NC 27710;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward R.","family":"Horton","sequence":"additional","affiliation":[{"name":"Harvard Reproductive Endocrine Sciences Center &amp; Reproductive Endocrine Unit of the Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni P.","family":"Asimacopoulos","sequence":"additional","affiliation":[{"name":"Otology and Laryngology, and"},{"name":"Department of Otolaryngology, Massachusetts Eye &amp; Ear Infirmary, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina M.","family":"Stankovic","sequence":"additional","affiliation":[{"name":"Otology and Laryngology, and"},{"name":"Department of Otolaryngology, Massachusetts Eye &amp; Ear Infirmary, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacey","family":"Plummer","sequence":"additional","affiliation":[{"name":"Harvard Reproductive Endocrine Sciences Center &amp; Reproductive Endocrine Unit of the Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra L.","family":"Buck","sequence":"additional","affiliation":[{"name":"Harvard Reproductive Endocrine Sciences Center &amp; Reproductive Endocrine Unit of the Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Quinton","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne NE1 3BZ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd D.","family":"Nebesio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Mericq","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research, University of Chile, Casilla 226-3, Santiago, Chile; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8725-6348","authenticated-orcid":false,"given":"Paulina M.","family":"Merino","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research, University of Chile, Casilla 226-3, Santiago, Chile; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian F.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Genetics, King Faisal Specialist Hospital &amp; Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Monies","sequence":"additional","affiliation":[{"name":"Department of Genetics, King Faisal Specialist Hospital &amp; Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Gusella","sequence":"additional","affiliation":[{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114; 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