{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:01:28Z","timestamp":1760151688239,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Slovenian Research Agency","award":["research core funding No. P3-0343"],"award-info":[{"award-number":["research core funding No. P3-0343"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pathogenic variants within the gene encoding the pituitary-specific transcription factor, POU class 1 homeobox 1 (POU1F1), are associated with combined pituitary hormone deficiency (CPHD), including growth hormone, prolactin, and thyrotropin stimulating hormone deficiencies. The aim of the study was to identify genetic aetiology in 10 subjects with CPHD from four consanguineous Sudanese families. Medical history, as well as hormonal and radiological information, was obtained from participants\u2019 medical records. Targeted genetic analysis of the POU1F1 gene was performed in two pedigrees with a typical combination of pituitary deficiencies, using Sanger sequencing, and whole-exome sequencing was performed in the other two pedigrees, where hypocortisolism and additional neurologic phenotypes were also initially diagnosed. In POU1F1 gene (NM_001122757.2) a novel homozygous splice-site deletion\u2014namely, c.744-5_749del\u2014was identified in all 10 tested affected family members as a cause of CPHD. Apart from typical pituitary hormonal deficiencies, most patients had delayed but spontaneous puberty; however, one female had precocious puberty. Severe post-meningitis neurologic impairment was observed in three patients, of whom two siblings had Dyke\u2013Davidoff\u2013Masson syndrome, and an additional distantly related patient suffered from cerebral infarction. Our report adds to the previously reported POU1F1 gene variants causing CPHD and emphasises the importance of genetic testing in countries with high rates of consanguineous marriage such as Sudan. Genetic diagnostics elucidated that the aetiologies of hypopituitarism and brain abnormalities, identified in a subset of affected members, were separate. Additionally, as central hypocortisolism is not characteristic of POU1F1 deficiency, hydrocortisone replacement therapy could be discontinued. Elucidation of a genetic cause, therefore, contributed to the more rational clinical management of hypopituitarism in affected family members.<\/jats:p>","DOI":"10.3390\/genes13040657","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T12:11:14Z","timestamp":1649419874000},"page":"657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Splice-Site Deletion in the POU1F1 Gene Causes Combined Pituitary Hormone Deficiency in Multiple Sudanese Pedigrees"],"prefix":"10.3390","volume":"13","author":[{"given":"Samar S.","family":"Hassan","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, Gaafar Ibn Auf Pediatric Tertiary Hospital, Khartoum 11114, Sudan"},{"name":"Sudan Childhood Diabetes Center, Khartoum 11111, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, Gaafar Ibn Auf Pediatric Tertiary Hospital, Khartoum 11114, Sudan"},{"name":"Sudan Childhood Diabetes Center, Khartoum 11111, Sudan"},{"name":"Department of Pediatrics, Faculty of Medicine, University of Khartoum, Khartoum 11115, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-3547","authenticated-orcid":false,"given":"Katarina","family":"Trebusak Podkrajsek","sequence":"additional","affiliation":[{"name":"Clinical Institute of Special Laboratory Diagnostics, University Children\u2019s Hospital, Ljubljana University Medical Centre, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salwa","family":"Musa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, Gaafar Ibn Auf Pediatric Tertiary Hospital, Khartoum 11114, Sudan"},{"name":"Sudan Childhood Diabetes Center, Khartoum 11111, Sudan"},{"name":"Department of Pediatrics and Child Health Faculty of Medicine, Al-Neelain University, Khartoum 11121, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Areej","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Sudan Childhood Diabetes Center, Khartoum 11111, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omer","family":"Babiker","sequence":"additional","affiliation":[{"name":"Sudan Childhood Diabetes Center, Khartoum 11111, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3080-4838","authenticated-orcid":false,"given":"Jernej","family":"Kovac","sequence":"additional","affiliation":[{"name":"Clinical Institute of Special Laboratory Diagnostics, University Children\u2019s Hospital, Ljubljana University Medical Centre, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0273-4732","authenticated-orcid":false,"given":"Tadej","family":"Battelino","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Department of Paediatric Endocrinology, Diabetes and Metabolism, University Children\u2019s Hospital, Ljubljana University Medical Centre, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0836-5114","authenticated-orcid":false,"given":"Magdalena","family":"Avbelj Stefanija","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Department of Paediatric Endocrinology, Diabetes and Metabolism, University Children\u2019s Hospital, Ljubljana University Medical Centre, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2103","DOI":"10.1210\/clinem\/dgz184","article-title":"The molecular basis of congenital hypopituitarism and related disorders","volume":"105","author":"Gregory","year":"2020","journal-title":"J. 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