{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:23:37Z","timestamp":1787660617869,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Congenital anomalies of the kidney and urinary tract (CAKUT) are clinically heterogeneous and remain genetically unexplained in many patients. Biallelic variants in\n CTU2<\/jats:italic>\n have been reported in DREAM\u2010PL syndrome, a severe multisystem disorder characterized by dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. However, to date, there have been no reports on the involvement of\n CTU2<\/jats:italic>\n in CAKUT.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Exome sequencing (ES) was performed in 200 patients with CAKUT. Candidate\n CTU2<\/jats:italic>\n variants were validated by Sanger sequencing, and segregation analysis was conducted in available family members. Variant rarity was assessed using public population databases and an in\u2010house cohort of 200 ethnically matched kidney disease\u2010free controls. Potential functional effects were evaluated using in silico prediction tools and minigene splicing assays\n .<\/jats:italic>\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The affected individual, who had a diagnosis of CAKUT, presented with bilateral hydronephrosis, chronic kidney disease, and focal segmental glomerulosclerosis. Genetic analysis revealed compound heterozygous\n CTU2<\/jats:italic>\n variants, NM_001012759.3: c.913C>T, p.(Arg305Trp), and c.1492C>G, p.(Gln498Glu), which were inherited from his father and mother, respectively. Both variants were rare and had not been previously reported in\n CTU2<\/jats:italic>\n \u2010related disease.\n In silico<\/jats:italic>\n splicing analyses suggested that both variants may alter putative exonic splicing enhancers (ESE) motifs. Minigene splicing assays showed that c.913C>T altered pre\u2010mRNA splicing by increasing exon 9 skipping, whereas c.1492C>G had no statistically significant effect on exon inclusion.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study identifies two rare\n CTU2<\/jats:italic>\n variants in an individual with renal\u2010predominant CAKUT and provides in\u00a0vitro evidence that c.913C>T partially alters splicing. While these findings do not establish\n CTU2<\/jats:italic>\n as a definitive cause of isolated CAKUT, they support further case collection and kidney\u2010relevant functional studies of\n CTU2<\/jats:italic>\n in renal developmental phenotypes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70277","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:42:21Z","timestamp":1785217341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rare Biallelic\n \n CTU2<\/i>\n <\/scp>\n Variants in an Individual With\n CAKUT<\/scp>\n : Clinical Characterization and Minigene Splicing Analysis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6361-0467","authenticated-orcid":false,"given":"Qian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nephrology Children's Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Nephrology Children's Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3457-6545","authenticated-orcid":false,"given":"Bixia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-4807","authenticated-orcid":false,"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7438-4404","authenticated-orcid":false,"given":"Aihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Children's Hospital of Nanjing Medical University Nanjing Jiangsu 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