{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:07:45Z","timestamp":1777457265480,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.171123.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000}}],"reference-count":13,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/Y007808\/1"],"award-info":[{"award-number":["MR\/Y007808\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["Paed_RP_001_20180925"],"award-info":[{"award-number":["Paed_RP_001_20180925"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["RP_007_20210729"],"award-info":[{"award-number":["RP_007_20210729"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012357","name":"LifeArc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012357","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018693","name":"Horizon Europe","doi-asserted-by":"crossref","award":["UKRIundergrantagreementNo:101080717"],"award-info":[{"award-number":["UKRIundergrantagreementNo:101080717"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Autosomal recessive polycystic kidney disease (ARPKD) is a rare, inherited disorder primarily affecting the kidneys and liver. Disease-causing variants in\n                    <ns3:italic>PKHD1<\/ns3:italic>\n                    lead to a disruption of the encoded protein fibrocystin\/polyductin. This study aims to identify disease causing variants in\n                    <ns3:italic>PKHD1<\/ns3:italic>\n                    in families from the Dhofar region of Oman. Methods We conducted a case series of six families with antenatal diagnoses of ARPKD and postnatal deaths. Genetic testing was performed on neonates using Sanger sequencing and next-generation sequencing (NGS) to detect variants in\n                    <ns3:italic>PKHD1.<\/ns3:italic>\n                    <ns3:italic>In silico<\/ns3:italic>\n                    analysis of mutational consequences was performed. Results 5 distinct homozygous variants in the\n                    <ns3:italic>PKHD1<\/ns3:italic>\n                    gene were identified, including three pathogenic frameshift variants (c.6111_6112delTT, c.7011dupT and c.9550dupT), a nonsense variant (c.340C&gt;T) and a homozygous deletion spanning exons 58-60 of the\n                    <ns3:italic>PKHD1.<\/ns3:italic>\n                    These alleles have not been reported in previous studies.\n                    <ns3:italic>In silico<\/ns3:italic>\n                    modelling identified pathogenic alleles, predicted to lead to either truncated protein products or nonsense-mediated decay. Discussion Our findings identify disease causing\n                    <ns3:italic>PKHD1<\/ns3:italic>\n                    variants in this genetically distinct Dhofar population, potentially due to factors such as geographical isolation, consanguinity, and founder effects. The identification of previously undescribed variants underscores the need for regional genetic studies in understanding ARPKD and its genotype-phenotype correlations. Conclusion This study reveals distinct\n                    <ns3:italic>PKHD1<\/ns3:italic>\n                    disease-causing variants in the Dhofar region of Oman, contributing to the broader genetic understanding of ARPKD. These findings highlight the value of region-specific genetic research in identifying new disease causing variants.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.171123.2","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T09:14:07Z","timestamp":1777022047000},"page":"1212","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6674-7276","authenticated-orcid":false,"given":"Intisar","family":"Al Alawi","sequence":"first","affiliation":[{"name":"National Genetic Centre Muscat Ministry of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maha","family":"Al Awadi","sequence":"additional","affiliation":[{"name":"Sultan Qaboos Hospital Salalah Ministry of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma","family":"Al Awaid","sequence":"additional","affiliation":[{"name":"Sultan Qaboos Hospital Salalah Ministry of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2477-1868","authenticated-orcid":false,"given":"Joshua","family":"Pillai","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology Boston MA Boston Children's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Sampson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology Boston MA Boston Children's Hospital"},{"name":"Boston Massachusetts Harvard Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana E.","family":"Arcila Galvis","sequence":"additional","affiliation":[{"name":"Biosciences Institute Newcastle Upon Tyne Newcastle University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4695-9448","authenticated-orcid":false,"given":"Ashwaq","family":"Al Maimani","sequence":"additional","affiliation":[{"name":"National Genetic Centre Muscat Ministry of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zainab","family":"Al Hashmi","sequence":"additional","affiliation":[{"name":"National Genetic Centre Muscat Ministry of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-3782","authenticated-orcid":false,"given":"John A.","family":"Sayer","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology Boston MA Boston Children's Hospital"},{"name":"Biosciences Institute Newcastle Upon Tyne Newcastle University"},{"name":"Renal Services Newcastle upon Tyne England Newcastle Upon Tyne Hospitals NHS Foundation Trust"},{"name":"Newcastle upon Tyne England NIHR Newcastle Biomedical Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"493-500","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3.","volume":"630","author":"J Abramson","year":"2024","journal-title":"Nature."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1751-1759","DOI":"10.1016\/j.ekir.2019.08.012","article-title":"Molecular Genetic Diagnosis of Omani Patients With Inherited Cystic Kidney Disease.","volume":"4","author":"I Al Alawi","year":"2019","journal-title":"Kidney Int Rep."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1186\/s12882-020-02013-2","article-title":"Clinical and genetic characteristics of autosomal recessive polycystic kidney disease in Oman.","volume":"21","author":"I Al Alawi","year":"2020","journal-title":"BMC Nephrol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e444","DOI":"10.5001\/omj.2022.101","article-title":"Prevalence and Characteristics of Cystic Fibrosis in Omani Children: A Multi-center Cross-sectional Study.","volume":"37","author":"S Al Oraimi","year":"2022","journal-title":"Oman Med. 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Pediatr."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2189-2191","DOI":"10.1093\/bioinformatics\/btl123","article-title":"G8: a novel domain associated with polycystic kidney disease and non-syndromic hearing loss.","volume":"22","author":"Q He","year":"2006","journal-title":"Bioinformatics."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"677-689","DOI":"10.1016\/S0969-2126(97)00222-0","article-title":"Two crystal structures of pectin lyase A from Aspergillus reveal a pH driven conformational change and striking divergence in the substrate-binding clefts of pectin and pectate lyases.","volume":"5","author":"O Mayans","year":"1997","journal-title":"Structure."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"891","DOI":"10.12688\/f1000research.6938.1","article-title":"Repository of mutations from Oman: The entry point to a national mutation database.","volume":"4","author":"A Rajab","year":"2015","journal-title":"F1000Res."},{"key":"ref12","article-title":"PYMOL.","author":"L Schr\u00f6dinger","year":"2020"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"215-229","DOI":"10.1002\/pd.1970080308","article-title":"Autosomal recessive polycystic kidney disease. Problems of prenatal diagnosis.","volume":"8","author":"K Zerres","year":"1988","journal-title":"Prenat. Diagn."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-1212\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-1212\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-1212\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:04:07Z","timestamp":1777381447000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-1212\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":13,"URL":"https:\/\/doi.org\/10.12688\/f1000research.171123.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.171123.1","asserted-by":"subject"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-1212\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.188677.r447908, Hana Yang, Mayo Clinic Minnesota, Rochester, Minnesota, 13 Jan 2026, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1212\/v1#referee-response-447908","order":0,"name":"referee-response-447908","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.188677.r450003, Consolato M Sergi, Children\u2019s Hospital of Eastern Ontario, Ontario, 29 Jan 2026, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-1212\/v1#referee-response-450003","order":1,"name":"referee-response-450003","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"J.A.G. is funded by MRC (MR\/Y007808\/1). J.A.S. is funded by LifeArc, Medical Research Council (MR\/Y007808\/1), Kidney Research UK (Paed_RP_001_ 20180925, RP_007_20210729), the Northern Counties Kidney Research Fund (20\/01) and the European Union\u2019s Horizon Europe research and innovation programme and from UKRI under grant agreement No: 101080717 (TheRaCil). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}