{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:28:37Z","timestamp":1793035717935,"version":"4.5.0"},"reference-count":6,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heterozygous loss\u2010of\u2010function variants in the <jats:italic>PKD1<\/jats:italic> gene are commonly associated with adult\u2010onset autosomal dominant polycystic kidney disease (ADPKD), where the formation of renal cysts depends on the dosage of the <jats:italic>PKD1<\/jats:italic> gene. Biallelic null <jats:italic>PKD1<\/jats:italic> variants are not viable, but biallelic hypomorphic variants could lead to early\u2010onset PKD. We report a non\u2010consanguineous Chinese family with recurrent fetal polycystic kidney and negative findings in the coding region of the <jats:italic>PKHD1<\/jats:italic> gene or chromosomal microarray analysis. Trio exome analysis revealed compound heterozygous variants of uncertain significance in the <jats:italic>PKD1<\/jats:italic> gene in the index pregnancy: a novel paternally inherited c.7863 + 5G &gt; C and a maternally inherited c.9739C &gt; T, p.(Arg3247Cys). Segregation analysis through long\u2010range PCR followed by nested PCR and Sanger sequencing confirmed another affected fetus had both variants, while the other two normal siblings and the parents carried either variant. Thus, these two variants, both of which were hypomorphic as opposed to null variants, co\u2010segregated with prenatal onset polycystic kidney disease in this family. Functional studies are needed to further determine the impact of these two variants. Our findings highlight the biallelic inheritance of hypomorphic <jats:italic>PKD1<\/jats:italic> variants causing prenatal onset polycystic kidney disease, which provides a better understanding of phenotype\u2010genotype correlation and valuable information for reproductive counseling.<\/jats:p>","DOI":"10.1002\/pd.6419","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T08:53:58Z","timestamp":1692435238000},"page":"247-250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Prenatal diagnosis of polycystic kidney caused by biallelic hypomorphic variants in the <i>PKD1<\/i> gene"],"prefix":"10.1002","volume":"44","author":[{"given":"Yu","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4140-6651","authenticated-orcid":false,"given":"Angel Hoi Wan","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirui","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Yin","family":"Kwok","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-6200","authenticated-orcid":false,"given":"Kwong Wai","family":"Choy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Baylor Genetics  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-1968","authenticated-orcid":false,"given":"Ye","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010018\u20100582\u2010x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep30850"},{"key":"e_1_2_10_5_1","first-page":"1993","volume-title":"GeneReviews\u00ae [Internet]","author":"Harris PC","year":"2002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64313"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010020\u201001026\u20104"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6419","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T19:02:12Z","timestamp":1708110132000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.6419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,19]]},"references-count":6,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/pd.6419"],"URL":"https:\/\/doi.org\/10.1002\/pd.6419","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,19]]},"assertion":[{"value":"2023-05-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}