{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:40:48Z","timestamp":1775148048178,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20K17275"],"award-info":[{"award-number":["20K17275"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>The impact of rare pathogenic variants on diabetic kidney disease (DKD) has not been investigated in detail. Previous studies have detected pathogenic variants in 22% of Caucasian patients with DKD; however, this proportion may vary depending on ethnicity and updates to the database. Therefore, we performed a whole\u2010genome analysis of patients with DKD in type 2 diabetes mellitus in Japan, utilizing a recent database to investigate the prevalence of kidney\u2010related pathogenic variants and describe the characteristics of these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Whole\u2010genome sequencing was performed, and variants were analyzed following the GATK Best Practices. We extracted data on 790 genes associated with Mendelian kidney and genitourinary diseases. Pathogenic variants were defined based on the American College of Medical Genetics criteria, including both heterozygous and homozygous variants classified as pathogenic or likely pathogenic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 79 participants, heterozygous pathogenic variants were identified in 27 (34.1%), a higher prevalence than previously reported. No homozygous pathogenic variants were detected. The identified heterozygous pathogenic variants were roughly divided into 23.7% related to glomerulopathy, 36.8% related to tubulointerstitial disease, 10.5% related to cystic disease\/ciliopathy, and 28.9% related to others. Diagnostic variants were found in 10 patients (12.7%) in seven genes (<jats:italic>ABCC6, ALPL, ASXL1<\/jats:italic>, <jats:italic>BMPR2<\/jats:italic>, <jats:italic>GCM2, PAX2<\/jats:italic>, and <jats:italic>WT1<\/jats:italic>), all associated with autosomal dominant congenital disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study identified a considerable number of patients with DKD in Japan who carried kidney\u2010related heterozygous pathogenic variants. These findings suggest potential ethnic differences and highlight the impact of database updates on variant detection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.70041","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T12:21:31Z","timestamp":1744114891000},"page":"1263-1273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pathogenic variants prevalence patients with diabetic kidney disease in Japan: A descriptive study"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9755-0935","authenticated-orcid":false,"given":"Toyohiro","family":"Hashiba","sequence":"first","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3022-1096","authenticated-orcid":false,"given":"Yuka","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Hirakawa","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dai","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reiko","family":"Inagi","sequence":"additional","affiliation":[{"name":"Division of Chronic Kidney Disease Pathophysiology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2021-002146"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/kidneydial2030038"},{"issue":"2","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1053\/j.ajkd.2006.12.005","article-title":"KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease","volume":"49","author":"KDOQI","year":"2007","journal-title":"Am J Kidney Dis"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.37"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0332-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05735-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2188\/jea.JE20230281"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08494"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1806891"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000514578"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000249"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-022-04944-z"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310345"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2314761"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-024-01316-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2024.01.027"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab044"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208654"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-20638-1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.10.039"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.7326\/M20-0529"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.12.034"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-016-1252-1"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13249"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000522226"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfab218"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43657-021-00014-1"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00305"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-16-S19-S5"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-85182-w"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1034"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2796-6"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.03.031"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13010123"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019020152"},{"key":"e_1_2_8_40_1","unstructured":"ClinVar submissions [Internet]. [Accessed 2024 May 15]. Available fromhttps:\/\/www.ncbi.nlm.nih.gov\/clinvar\/submitters\/."},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-023-06073-y"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfy028"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-022-01020-5"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14081562"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2023-109563"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.119.303006"}],"container-title":["Journal of Diabetes Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.70041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:48:03Z","timestamp":1754905683000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdi.70041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1111\/jdi.70041"],"URL":"https:\/\/doi.org\/10.1111\/jdi.70041","archive":["Portico"],"relation":{},"ISSN":["2040-1116","2040-1124"],"issn-type":[{"value":"2040-1116","type":"print"},{"value":"2040-1124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,8]]},"assertion":[{"value":"2024-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}