{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:47:37Z","timestamp":1783435657188,"version":"3.54.6"},"reference-count":82,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Saudi human genome program (SHGP)","award":["2018-36"],"award-info":[{"award-number":["2018-36"]}]},{"name":"Saudi human genome program (SHGP)","award":["S-1441-0080"],"award-info":[{"award-number":["S-1441-0080"]}]},{"DOI":"10.13039\/100009391","name":"Deanship of Scientific Research (DSR), University of Tabuk, Tabuk","doi-asserted-by":"publisher","award":["2018-36"],"award-info":[{"award-number":["2018-36"]}],"id":[{"id":"10.13039\/100009391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009391","name":"Deanship of Scientific Research (DSR), University of Tabuk, Tabuk","doi-asserted-by":"publisher","award":["S-1441-0080"],"award-info":[{"award-number":["S-1441-0080"]}],"id":[{"id":"10.13039\/100009391","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G &gt; A). Two missense mutations were identified with a PKD1 (c.1758A &gt; C and c.9774T &gt; G), and one patient had a PKD2 mutation (c.1445T &gt; G). Three detected variants were novel, identified at PKD1 (c.1758A &gt; C), PKD2L2 (c.1364A &gt; T), and TSC2 (deletion of a\u2019a at the 3\u2019UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C &gt; T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3\u2019UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein\u2013protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended.<\/jats:p>","DOI":"10.3390\/medicina58111657","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:24:34Z","timestamp":1668655474000},"page":"1657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2726-0473","authenticated-orcid":false,"given":"Othman R.","family":"Alzahrani","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan E.","family":"Alatwi","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-9508","authenticated-orcid":false,"given":"Amnah A.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Department of Biochemistry, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman H.","family":"Alessa","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama M.","family":"Al-Amer","sequence":"additional","affiliation":[{"name":"Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer F. R.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biological Sciences, UCL School of Pharmacy, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9888-2739","authenticated-orcid":false,"given":"Anwar M.","family":"Shams","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-9336","authenticated-orcid":false,"given":"Esra\u2019a","family":"Alomari","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman 11622, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-7446","authenticated-orcid":false,"given":"Abdallah Y.","family":"Naser","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman 11622, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0441-4000","authenticated-orcid":false,"given":"Faisal a.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of science, Embryonic Stem Cell Unit, King Fahad Center for Medical Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-1618","authenticated-orcid":false,"given":"Salman","family":"Hosawi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, King AbdulAziz University, Jeddah 21589, Saudi Arabia"},{"name":"Artificial Intelligence in Systems Biology Research Unit, The King Abdulaziz University and The University of Oxford Center for Artificial Intelligence for Precision Medicine, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-0486","authenticated-orcid":false,"given":"Saeed M.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Department of Medicine, King Faisal Specialist Hospital and Research Centre, P.O. Box 40047, Jeddah 21499, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wed A.","family":"Abdali","sequence":"additional","affiliation":[{"name":"Research Center, King Faisal Specialist Hospital and Research Center, MBC J04, P.O. Box 40047, Jeddah 21499, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imadeldin","family":"Elfaki","sequence":"additional","affiliation":[{"name":"Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Department of Biochemistry, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1901-697X","authenticated-orcid":false,"given":"Yousef M.","family":"Hawsawi","sequence":"additional","affiliation":[{"name":"Research Center, King Faisal Specialist Hospital and Research Center, MBC J04, P.O. Box 40047, Jeddah 21499, Saudi Arabia"},{"name":"College of Medicine, Al-Faisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1681\/ASN.2007030299","article-title":"Polycystic kidney disease","volume":"18","author":"Igarashi","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41572-018-0047-y","article-title":"Polycystic kidney disease","volume":"4","author":"Bergmann","year":"2018","journal-title":"Nat. Rev. Dis. 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