{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:29:57Z","timestamp":1786480197787,"version":"build-2736575974"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","funder":[{"name":"Grants-in-Aid for Scientific Research","award":["18K15712"],"award-info":[{"award-number":["18K15712"]}]},{"name":"Grants-in-Aid for Scientific Research","award":["26293203"],"award-info":[{"award-number":["26293203"]}]},{"name":"Grants-in-Aid for Scientific Research","award":["17H04189"],"award-info":[{"award-number":["17H04189"]}]},{"name":"Grants-in-Aid for Scientific Research","award":["19K08726"],"award-info":[{"award-number":["19K08726"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19ek0109231s0103"],"award-info":[{"award-number":["19ek0109231s0103"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ek0109231h0003"],"award-info":[{"award-number":["JP19ek0109231h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2020,9]]},"abstract":"\n Background<\/jats:title>\n \n Autosomal recessive Alport syndrome (ARAS) is an inherited renal disorder caused by homozygous and compound heterozygous mutations in\n COL4A3<\/jats:italic>\n or\n COL4A4<\/jats:italic>\n , but the prognostic predictors for this disorder are not yet fully understood. Recently, the magnitude of the clinical spectrum of the\n COL4A3<\/jats:italic>\n and\n COL4A4<\/jats:italic>\n heterozygous state has attracted attention. This spectrum includes asymptomatic carriers of ARAS, benign familial hematuria, thin basement membrane disease, and autosomal dominant Alport syndrome.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We retrospectively analyzed 49 patients with ARAS from 41 families with a median age of 19 years to examine the clinical features and prognostic factors of ARAS, including the associated genotypes.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The median age of patients with ARAS at ESKD onset was 27 years. There was no significant association between the presence or absence of hearing loss or truncating mutations and renal prognosis. However, there was a statistically significant correlation between renal prognosis and heterozygous variants that cause urinary abnormalities. Where the urinary abnormality\u2013causing variant was absent or present in only one allele, the median age of ESKD onset was 45 years, whereas the same variant present on both alleles was associated with an age of onset of 15 years (\n P<\/jats:italic>\n <0.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This study was the first to demonstrate the clinical importance in ARAS of focusing on variants in\n COL4A3<\/jats:italic>\n or\n COL4A4<\/jats:italic>\n that cause urinary abnormalities in both the homozygous or heterozygous state. Although heterozygous mutation carriers of\n COL4A3<\/jats:italic>\n and\n COL4A4<\/jats:italic>\n comprise a broad clinical spectrum, clinical information regarding each variant is important for predicting ARAS prognosis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000372019","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T21:55:16Z","timestamp":1594936516000},"page":"936-942","source":"Crossref","is-referenced-by-count":6,"title":["Heterozygous Urinary Abnormality\u2013Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome"],"prefix":"10.34067","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1655-6030","authenticated-orcid":false,"given":"Tomoko","family":"Horinouchi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"China","family":"Nagano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Sakakibara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ishiko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Aoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rini","family":"Rossanti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Uehara, Nishihara-cho, Tyutou, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Shima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wakayama Medical University, Kimiidera, Wakayama, Wakayama Prefecture, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Morisada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumoto","family":"Iijima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandai","family":"Nozu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo, Kobe, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"B1-20230821","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1681\/ASN.V991736","article-title":"Alport syndrome and thin glomerular basement membrane disease","volume":"9","author":"Kashtan","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"B2-20230821","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1681\/ASN.2012100985","article-title":"COL4A3\/COL4A4 mutations and features in individuals with autosomal recessive Alport syndrome","volume":"24","author":"Storey","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B3-20230821","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1093\/ndt\/17.7.1218","article-title":"Meta-analysis of genotype-phenotype correlation in X-linked Alport syndrome: Impact on clinical counselling","volume":"17","author":"Gross","year":"2002","journal-title":"Nephrol Dial 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Res"}],"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000372019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T19:57:06Z","timestamp":1786478226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000372019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":25,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.34067\/kid.0000372019","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]}}}