{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:41:20Z","timestamp":1787992880181,"version":"build-2784847793"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ30715"],"award-info":[{"award-number":["2023JJ30715"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","award":["2023ZZTS0869"],"award-info":[{"award-number":["2023ZZTS0869"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800219"],"award-info":[{"award-number":["81800219"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Aim<\/jats:title>\n Autosomal dominant polycystic kidney disease (ADPKD), the most common form of PKD, is a prevalent monogenic multi\u2010system disorder, characterised by progressive enlargement of fluid\u2010filled cysts. This study was designed to identify the underlying genetic causes in two ADPKD\u2010afflicted Han\u2010Chinese families.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A total of 10 individuals from two ADPKD\u2010afflicted Han\u2010Chinese families were recruited. Whole exome sequencing and Sanger sequencing were performed to identify possible causal variants. In silico analysis for variants' pathogenicity was performed, and an in\u00a0vitro minigene splicing system was further utilised to assess the effect of the splice variant on pre\u2010mRNA splicing.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A heterozygous splice variant, c.11538\u20102A>G, in the polycystin 1, transient receptor potential channel interacting gene (\n PKD1<\/jats:italic>\n ), and a novel heterozygous nonsense variant, c.2387T>G [p.(Leu796*)], in the polycystin 2, transient receptor potential cation channel gene (\n PKD2<\/jats:italic>\n ), were identified in probands of the two ADPKD families, respectively, as well as the affected individuals, confirmed by Sanger sequencing. In silico analysis predicted these variants to be deleterious. In\u00a0vitro minigene splicing assay established that the c.11538\u20102A>G variant could cause complete exon 42 skipping, which was predicted to lead to a truncated protein.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n A splice variant, c.11538\u20102A>G, in the\n PKD1<\/jats:italic>\n gene and a novel nonsense variant, c.2387T>G [p.(Leu796*)], in the\n PKD2<\/jats:italic>\n gene were identified as the genetic drivers of ADPKD in two Han\u2010Chinese families, respectively. This study may help pave the way to illustrate the underlying mechanism of ADPKD and possibly provide some new clues for specific management and therapeutics.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nep.70135","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:42:07Z","timestamp":1760416927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PKD1<\/i>\n Splice and\n PKD2<\/i>\n Nonsense Variants Identified in Two Chinese Families With Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1111","volume":"30","author":[{"given":"Zexuan","family":"Li","sequence":"first","affiliation":[{"name":"Health Management Center, the Third Xiangya Hospital, Central South University Changsha China"},{"name":"Center for Experimental Medicine, the Third Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, the Third Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, the Third Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Deng","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, the Third Xiangya Hospital, Central South University Changsha China"},{"name":"Xiangya School of Medicine, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, the Third Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Third Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2049-3485","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, the Third Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangang","family":"Wang","sequence":"additional","affiliation":[{"name":"Health Management Center, the Third Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Health Management Center, the Third Xiangya Hospital, Central South University Changsha China"},{"name":"Center for Experimental Medicine, the Third Xiangya Hospital, Central South University Changsha China"},{"name":"Disease Genome Research Center, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3240-4352","authenticated-orcid":false,"given":"Hao","family":"Deng","sequence":"additional","affiliation":[{"name":"Health Management Center, the Third Xiangya Hospital, Central South University Changsha China"},{"name":"Center for Experimental Medicine, the Third Xiangya Hospital, Central South University Changsha China"},{"name":"Disease Genome Research Center, Central South University Changsha China"},{"name":"Research Center of Medical Experimental Technology, the Third Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0051-1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0047-y"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2014.05.005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13071020"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0155-2"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2010.18"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017050483"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2021.09.013"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/nep.14287"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-00796-4"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2017.01.046"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2023.01.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67273"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/nep.14390"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008050507"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-7178"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20192510"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16866"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcad010"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015010016"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-020-04869-w"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.60.101707.125712"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0582-8"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0143-6"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009020162"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat9819"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22103"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/43907"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0697-179"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209996200"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000522377"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2316230121"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270933"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109490"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.40.28557"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005090979"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/35050128"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfx071"}],"container-title":["Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.70135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T03:45:49Z","timestamp":1761536749000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nep.70135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":39,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/nep.70135"],"URL":"https:\/\/doi.org\/10.1111\/nep.70135","archive":["Portico"],"relation":{},"ISSN":["1320-5358","1440-1797"],"issn-type":[{"value":"1320-5358","type":"print"},{"value":"1440-1797","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70135"}}