{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:04:25Z","timestamp":1790226265455,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004186","name":"Northwest Regional Development Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004186","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012095","name":"Scottish Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012095","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Health"},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NHS England"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2023,7,28]]},"abstract":"<jats:p>Biallelic PKD1 variants, including hypomorphic variants, can cause very early onset polycystic kidney disease (VEO-PKD). A family with unexplained recurrent VEO-PKD and neonatal demise in one dizygotic twin was referred for clinical testing. Further individuals with the putative hypomorphic PKD1 variant, p.(Ile3167Phe), were identified from the UK 100,000 genomes project (100\u2009K), UK Biobank (UKBB), and a review of the literature. We identified a likely pathogenic PKD1 missense paternal variant and the putative hypomorphic PKD1 variant from the unaffected mother in the deceased twin but only the paternal PKD1 variant in the surviving dizygotic twin. Analysis of 100\u2009K cases identified a second family with two siblings with similar biallelic inheritance who presented at birth with VEO-PKD and reached kidney failure in their teens unlike other affected relatives. Finally, a survey of 618 UKBB cases confirmed that adult patients monoallelic for PKD1 p.(Ile3167Phe) had normal kidney function. Our data reveals that p.(Ile3167Phe) is the second most common PKD1 hypomorphic variant identified and is neutral in heterozygosity but is associated with VEO-PKD when inherited in trans with a pathogenic PKD1 variant. Care should be taken to ensure that it is not automatically filtered from sequence data for VEO cases.<\/jats:p>","DOI":"10.1155\/2023\/5597005","type":"journal-article","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T03:05:09Z","timestamp":1690599909000},"page":"1-8","source":"Crossref","is-referenced-by-count":4,"title":["The Common PKD1 p.(Ile3167Phe) Variant Is Hypomorphic and Associated with Very Early Onset, Biallelic Polycystic Kidney Disease"],"prefix":"10.1155","volume":"2023","author":[{"given":"Miranda","family":"Durkie","sequence":"first","affiliation":[{"name":"Sheffield Diagnostics Genetic Service, North East and Yorkshire Genomic Laboratory Hub, Sheffield Children\u2019s NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2371-1844","authenticated-orcid":true,"given":"Christopher M.","family":"Watson","sequence":"additional","affiliation":[{"name":"Leeds Genetics Laboratory, North East and Yorkshire Genomic Laboratory Hub, St. James\u2019s University Hospital, Leeds, UK"},{"name":"Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Winship","sequence":"additional","affiliation":[{"name":"Sheffield Diagnostics Genetic Service, North East and Yorkshire Genomic Laboratory Hub, Sheffield Children\u2019s NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Cecile","family":"Hogg","sequence":"additional","affiliation":[{"name":"Sheffield Diagnostics Genetic Service, North East and Yorkshire Genomic Laboratory Hub, Sheffield Children\u2019s NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Nyanhete","sequence":"additional","affiliation":[{"name":"Sheffield Diagnostics Genetic Service, North East and Yorkshire Genomic Laboratory Hub, Sheffield Children\u2019s NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Cooley","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology, Rotunda Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj K.","family":"Valluru","sequence":"additional","affiliation":[{"name":"Kidney Genetics Group, Academic Nephrology Unit, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Shaw-Smith","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Royal Devon University Healthcare NHS Foundation Trust, Gladstone Road, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coralie","family":"Bingham","sequence":"additional","affiliation":[{"name":"University of Exeter Medical School, Royal Devon University Healthcare NHS Foundation Trust, Barrack Road, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"University of Exeter Medical School, Royal Devon University Healthcare NHS Foundation Trust, Barrack Road, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna","family":"Kenny","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Children\u2019s Health Ireland, Crumlin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genomics England Research","family":"Consortium","sequence":"additional","affiliation":[{"name":"Genomics England Research Consortium, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-5400","authenticated-orcid":true,"given":"Albert C. M.","family":"Ong","sequence":"additional","affiliation":[{"name":"Kidney Genetics Group, Academic Nephrology Unit, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2484-x"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.686"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009101070"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014101051"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-01026-4"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100452"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010101080"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2293-3_6"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108704"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00464"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64313"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.207"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014111074"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2021.03.893"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0560-8"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/humu\/2023\/5597005.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/humu\/2023\/5597005.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/humu\/2023\/5597005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T03:05:17Z","timestamp":1690599917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/humu\/2023\/5597005\/"}},"subtitle":[],"editor":[{"given":"William","family":"Oetting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,28]]},"references-count":15,"alternative-id":["5597005","5597005"],"URL":"https:\/\/doi.org\/10.1155\/2023\/5597005","relation":{},"ISSN":["1098-1004"],"issn-type":[{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,28]]}}}