{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:54:07Z","timestamp":1785383647042,"version":"3.55.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["23K07698"],"award-info":[{"award-number":["23K07698"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Health, Labour and Welfare Sciences Research Grants","award":["23FC1047"],"award-info":[{"award-number":["23FC1047"]}]},{"name":"Health Labor Sciences Research Grant","award":["H29-nanchi-ippan-039"],"award-info":[{"award-number":["H29-nanchi-ippan-039"]}]},{"name":"Health Labor Sciences Research Grant","award":["23FC1047"],"award-info":[{"award-number":["23FC1047"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15K09261"],"award-info":[{"award-number":["JP15K09261"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K08243"],"award-info":[{"award-number":["18K08243"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K08351"],"award-info":[{"award-number":["22K08351"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019084","name":"Kobe University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019084","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Nephrol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Autosomal-dominant tubulointerstitial kidney disease caused by <jats:italic>MUC1<\/jats:italic> (ADTKD-<jats:italic>MUC1<\/jats:italic>) is a rare disorder characterized by progressive kidney dysfunction. Pathogenic variants in <jats:italic>MUC1<\/jats:italic> are difficult to detect owing to the variable number tandem repeat region. To address this issue, VNtyper-Kestrel, a bioinformatics pipeline for short-read sequencing data, was recently developed. In this study, the performance of VNtyper-Kestrel for detecting <jats:italic>MUC1<\/jats:italic> variants in clinical settings was evaluated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We used VNtyper-Kestrel to retrospectively analyze short-read sequencing data for 209 individuals with suspected ADTKD who were previously evaluated through long-read sequencing. Data from a panel including\u2009~\u2009180 genes and an ADTKD-specific panel were used. In addition, the pipeline was applied to 976 patients with suspected hereditary kidney diseases other than ADTKD and positive cases were validated using long-read sequencing. Accuracy was assessed by comparisons with the results of long-read sequencing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Using VNtyper-Kestrel, we identified <jats:italic>MUC1<\/jats:italic> variants in 16 of 19 confirmed cases of ADTKD-<jats:italic>MUC1<\/jats:italic>. Three initially negative cases were reanalyzed using the ADTKD-specific panel, yielding positive detection results with high confidence. We obtained two low-confidence positive results from 190 cases of suspected ADTKD and 10 low-confidence positive results among 976 non-ADTKD cases; however, all were classified as false positives upon long-read sequencing validation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>VNtyper-Kestrel demonstrated high sensitivity in identifying <jats:italic>MUC1<\/jats:italic> variants when sequencing coverage was adequate, supporting its potential as a rapid and cost-effective screening tool. However, confirmatory long-read sequencing is needed in uncertain cases. Optimizing coverage and refining patient selection criteria could improve the clinical utility of this approach.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10157-025-02675-y","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T08:20:13Z","timestamp":1744878013000},"page":"1192-1199","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical use of the VNtyper-Kestrel pipeline for MUC1 variant detection in autosomal-dominant tubulointerstitial kidney disease"],"prefix":"10.1007","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4946-1345","authenticated-orcid":false,"given":"China","family":"Nagano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Morisada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Inoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chika","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Kitakado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Aoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Sakakibara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Horinouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Yamamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Ishimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandai","family":"Nozu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"issue":"4","key":"2675_CR1","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/ki.2015.28","volume":"88","author":"KU Eckardt","year":"2015","unstructured":"Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, et al. 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Am J Kidney Dis. 2025. https:\/\/doi.org\/10.1053\/j.ajkd.2024.11.010.","journal-title":"Am J Kidney Dis"}],"container-title":["Clinical and Experimental Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-025-02675-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10157-025-02675-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-025-02675-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T18:02:52Z","timestamp":1758045772000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10157-025-02675-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["2675"],"URL":"https:\/\/doi.org\/10.1007\/s10157-025-02675-y","relation":{},"ISSN":["1342-1751","1437-7799"],"issn-type":[{"value":"1342-1751","type":"print"},{"value":"1437-7799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"assertion":[{"value":"4 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Kandai Nozu is a member of advisory groups for Kyowa Kirin Co. Ltd., Toa Eiyo Ltd., Zenyaku Kogyo Co. Ltd., and Taisho Pharmaceutical Co. Ltd. Kandai Nozu received lecture fees from Ono Pharma, Astellas Pharma, Novo Nordisk Pharma, Alexion Pharma, Sumitomo Pharma, Sanofi, Otsuka Pharma, Daiichi Sankyo, and Miyarisan. Kandai Nozu received grants from Zenyaku Kogyo and Torii Co. Ltd. Kandai Nozu received a patent for an exon skipping therapy for Alport syndrome. Tomoko Horinouchi received research funding from Otsuka Pharmaceutical Co., Ltd., Sysmex Corporation, and Zenyaku Kogyo Co., Ltd. All the other authors have nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All the procedures involving human participants were performed in accordance with the ethical standards of the Institutional Review Board of Kobe University Graduate School of Medicine (IRB approval number 301) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}