{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:55:28Z","timestamp":1760147728048,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taibah University","award":["442\/127"],"award-info":[{"award-number":["442\/127"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Combined pituitary hormone deficiency (CPHD) is a rare heterogeneous disease. It is characterized by the deficiency of growth hormone (GH) and shortage of at least one or more other hormones of the pituitary gland including thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Rare pathogenic variants in nearly 30 genes have been identified as an underlying cause of CPHD pathogenicity. Among these genes, paired-like homeobox 1 (PROP1) has been reported to be the most common cause of CPHD. Materials and Methods: In the present study, we investigated a large family of Saudi origin with three adult sisters suffering from short stature in combination of secondary amenorrhea. Results: Whole-exome sequencing followed by Sanger sequencing shows a homozygous missense variant (NM_006261.5; c.211C &gt; T; p.R71C) in the PROP1 gene segregating with the disease phenotype within the family. In silico analysis studies show that this variant is highly conserved among several orthologues and is predicted as likely pathogenic using various bioinformatics tools. Conclusions: Our finding presents the first Saudi familial case of autosomal recessive form of CPHD caused by the PROP1 variant.<\/jats:p>","DOI":"10.3390\/medicina59030474","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:00:38Z","timestamp":1677553238000},"page":"474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of Homozygous PROP1 Mutation in a Saudi Family with Combined Pituitary Hormone Deficiency"],"prefix":"10.3390","volume":"59","author":[{"given":"Ahmed","family":"Almatrafi","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, Centre for Genetics and Inherited Diseases, Taibah University Al Madinah, Al Munawarah 42353, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Hibshi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, King Sulman Medical City-Madinah Maternity and Children Hospital, Almadinah Almunawwarah 42319, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-6825","authenticated-orcid":false,"given":"Sulman","family":"Basit","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Centre for Genetics and Inherited Diseases, Taibah University Al Madinah, Al Munawarah 42353, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1055\/s-0042-117112","article-title":"Identification of novel PROP1 and POU1F1 mutations in patients with combined pituitary hormone deficiency","volume":"48","author":"Birla","year":"2016","journal-title":"Horm. 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