{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:08:10Z","timestamp":1760238490364,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T00:00:00Z","timestamp":1597104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["DEC-2012\/04\/M\/NZ5\/00475","DEC-2011\/03\/D\/NZ5\/06142"],"award-info":[{"award-number":["DEC-2012\/04\/M\/NZ5\/00475","DEC-2011\/03\/D\/NZ5\/06142"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome. We aimed to find contribution of rare copy number variations (CNVs). As a result, we identified genomic imbalances in 7 regions among 12 CPHD patients. Five out of seven regions showed copy gains whereas two presented losses of genomic fragment. Three regions with detected gains encompassed known CPHD genes namely LHX4, HESX1, and OTX2. Among new CPHD loci, the most interesting seem to be the region covering SIX3 gene, that is abundantly expressed in developing brain, and together with HESX1 contributes to pituitary organogenesis as it was evidenced before in functional studies. In conclusion, with the use of broadened genomic approach we identified copy number imbalances for 12 CPHD patients. Although further functional studies are required in order to estimate its true impact on expression pattern during pituitary organogenesis and CPHD etiology.<\/jats:p>","DOI":"10.3390\/ijms21165757","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T09:28:57Z","timestamp":1597138137000},"page":"5757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2860-395X","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Budny","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Karmelita-Katulska","sequence":"additional","affiliation":[{"name":"Department of General Radiology and Neuroradiology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Stajgis","sequence":"additional","affiliation":[{"name":"Department of General Radiology and Neuroradiology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"\u017bemojtel","sequence":"additional","affiliation":[{"name":"Genomics Platform, Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Institute of Bioorganic Chemistry, Polish Academy of Sciences, 60-569 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-7220","authenticated-orcid":false,"given":"Marek","family":"Rucha\u0142a","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-8834","authenticated-orcid":false,"given":"Katarzyna","family":"Ziemnicka","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S0014-5793(98)01234-4","article-title":"Human prop-1: Cloning, mapping, genomic structure. 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A"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/16\/5757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:59:15Z","timestamp":1760176755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/16\/5757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,11]]},"references-count":37,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21165757"],"URL":"https:\/\/doi.org\/10.3390\/ijms21165757","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2020,8,11]]}}}