{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:06:49Z","timestamp":1792667209107,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Wiedemann\u2010Rautenstrauch Syndrome (WRS; MIM 264090) is an extremely rare and highly heterogeneous syndrome that is inherited in a recessive fashion. The patients have hallmark features such as prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, facial dysmorphology, hypomyelination leukodystrophy, and mental impairment. Biallelic disease\u2010causing variants in the <jats:italic>RNA polymerase III subunit A<\/jats:italic> (<jats:italic>POLR3A<\/jats:italic>) have been associated with WRS. Here, we report the first identified cases of WRS syndrome with novel phenotypes in three consanguineous families (two Omani and one Saudi) characterized by biallelic variants in <jats:italic>POLR3A<\/jats:italic>. Using whole\u2010exome sequencing, we identified one novel homozygous missense variant (NM_007055: c.2456C&gt;T; p. Pro819Leu) in two Omani families and one novel homozygous variant (c.1895G&gt;T; p Cys632Phe) in Saudi family that segregates with the disease in the <jats:italic>POLR3A<\/jats:italic> gene. In silico homology modeling of wild\u2010type and mutated proteins revealed a substantial change in the structure and stability of both proteins, demonstrating a possible effect on function. By identifying the homozygous variants in the exon 14 and 18 of the <jats:italic>POLR3A<\/jats:italic> gene, our findings will contribute to a better understanding of the phenotype\u2010genotype relationship and molecular etiology of WRS syndrome.<\/jats:p>","DOI":"10.1002\/mgg3.2274","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T09:24:56Z","timestamp":1707816296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Further delineation of Wiedemann\u2010Rautenstrauch syndrome linked with <i>POLR3A<\/i>"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4149-9544","authenticated-orcid":false,"given":"Amjad","family":"Khan","sequence":"first","affiliation":[{"name":"Faculty of Science, Department of Biological Sciences (Zoology) University of Lakki Marwat  Lakki Marwat Pakistan"},{"name":"Institute for Medical Genetics and Applied Genomics University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Alexander von Humboldt Fellowship Foundation  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Al\u00a0Shamsi","sequence":"additional","affiliation":[{"name":"National Genetics Center The Royal Hospital, Ministry of Health  Muscat Sultanate of Oman"},{"name":"Child Health Department The Royal Hospital, Ministry of Health  Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Al\u00a0Shehhi","sequence":"additional","affiliation":[{"name":"National Genetics Center The Royal Hospital, Ministry of Health  Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna A.","family":"Kashgari","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Pediatrics, King Abdullah International Medical Research Centre (KAIMRC) King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard\u2010Health Affairs (MNGHA)  Riyadh Saudi Arabia"},{"name":"King Abdullah Specialized Children's Hospital (KASCH) Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaisha","family":"Al\u00a0Balushi","sequence":"additional","affiliation":[{"name":"National Genetics Center The Royal Hospital, Ministry of Health  Muscat Sultanate of Oman"},{"name":"Child Health Department The Royal Hospital, Ministry of Health  Muscat Sultanate of Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad A.","family":"Al\u00a0Dihan","sequence":"additional","affiliation":[{"name":"College of Medicine King Saud Bin Abdulaziz University for Health Sciences  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohannad A.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"College of Medicine King Saud Bin Abdulaziz University for Health Sciences  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abothnain","family":"Manal","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Pediatrics, King Abdullah International Medical Research Centre (KAIMRC) King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard\u2010Health Affairs (MNGHA)  Riyadh Saudi Arabia"},{"name":"King Abdullah Specialized Children's Hospital (KASCH) Ministry of National Guard Health Affairs  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Gonz\u00e1lez\u2010\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Bioscience Program, Bioengineering Program, Biological and Environmental Science and Engineering Division King Abdullah University of Science and Technology (KAUST)  Thuwal Kingdom of Saudi Arabia"},{"name":"Computational Biology Research Center King Abdullah University of Science and Technology  Thuwal Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan T.","family":"Arold","sequence":"additional","affiliation":[{"name":"Bioscience Program, Bioengineering Program, Biological and Environmental Science and Engineering Division King Abdullah University of Science and Technology (KAUST)  Thuwal Kingdom of Saudi Arabia"},{"name":"Computational Biology Research Center King Abdullah University of Science and Technology  Thuwal Kingdom of Saudi Arabia"},{"name":"Centre de Biologie Structurale (CBS), INSERM, CNRS Universit\u00e9 de Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa","family":"Eyaid","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Pediatrics, King Abdullah International Medical Research Centre (KAIMRC) King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard\u2010Health Affairs (MNGHA)  Riyadh Saudi Arabia"},{"name":"King Abdullah Specialized Children's Hospital (KASCH) Ministry of National Guard Health Affairs  Riyadh Saudi 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