{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:43Z","timestamp":1784557063004,"version":"3.55.0"},"reference-count":48,"publisher":"Bioscientifica","issue":"10","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,30]]},"abstract":"<jats:p>\n                    Because the causes of combined pituitary hormone deficiency (CPHD) are complex, the etiology of congenital CPHD remains unknown in most cases. The aim of the study was to identify the genetic etiology of CPHD in a well-defined single-center cohort. In total, 34 children (12 girls) with congenital CPHD (growth hormone (GH) deficiency and impaired secretion of at least one other pituitary hormone) treated with GH in our center were enrolled in the study. Their median age was 11.2 years, pre-treatment height was \u22123.2 s.d., and maximal stimulated GH was 1.4 ug\/L. Of them, 30 had central adrenal insufficiency, 27 had central hypothyroidism, ten had hypogonadotropic hypogonadism, and three had central diabetes insipidus. Twenty-six children had a midline defect on MRI. Children with clinical suspicion of a specific genetic disorder underwent genetic examination of the gene(s) of interest via Sanger sequencing or array comparative genomic hybridization. Children without a detected causal variant after the first-tier testing or with no suspicion of a specific genetic disorder were subsequently examined using next-generation sequencing growth panel. Variants were evaluated by the American College of Medical Genetics standards. Genetic etiology was confirmed in 7\/34 (21%) children. Chromosomal aberrations were found in one child (14q microdeletion involving the\n                    <jats:italic>OTX2<\/jats:italic>\n                    gene). The remaining 6 children had causative genetic variants in the\n                    <jats:italic>GLI2<\/jats:italic>\n                    ,\n                    <jats:italic>PROP1<\/jats:italic>\n                    ,\n                    <jats:italic>POU1F1<\/jats:italic>\n                    ,\n                    <jats:italic>TBX3<\/jats:italic>\n                    ,\n                    <jats:italic>PMM2<\/jats:italic>\n                    , and\n                    <jats:italic>GNAO1<\/jats:italic>\n                    genes, respectively. We elucidated the cause of CPHD in a fifth of the patients. Moreover, our study supports the\n                    <jats:italic>PMM2<\/jats:italic>\n                    gene as a candidate gene for CPHD and suggests pathogenic variants in the\n                    <jats:italic>GNAO1<\/jats:italic>\n                    gene as a potential novel genetic cause of CPHD.\n                  <\/jats:p>","DOI":"10.1530\/ec-24-0217","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T13:46:17Z","timestamp":1722347177000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":3,"title":["Etiology of combined pituitary hormone deficiency: GNAO1 as a novel candidate gene"],"prefix":"10.1530","volume":"13","author":[{"given":"Lukas","family":"Plachy","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8647-9088","authenticated-orcid":true,"given":"Petra","family":"Dusatkova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Maratova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenali Anne","family":"Amaratunga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Zemkova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vit","family":"Neuman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislava","family":"Kolouskova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbora","family":"Obermannova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Snajderova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenek","family":"Sumnik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lebl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stepanka","family":"Pruhova","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V \u00davalu, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endocrine Reviews","first-page":"636","article-title":"Genetics of combined pituitary hormone deficiency: roadmap into the genome era","volume":"37","author":"Fang","year":"2016","unstructured":"Fang QGeorge ASBrinkmeier MLMortensen AHGergics PCheung LYMDaly AZAjmal AP\u00e9rez Mill\u00e1n MIOzel AB, et al.Genetics of combined pituitary hormone deficiency: roadmap into the genome era. 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