{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:12:09Z","timestamp":1791994329739,"version":"4.4.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"name":"National Key Research and Development Program of China","award":["2020YFC2005003"],"award-info":[{"award-number":["2020YFC2005003"]}]},{"name":"National Science Foundation for Excellent Young Scholars","award":["81922013"],"award-info":[{"award-number":["81922013"]}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["81970598"],"award-info":[{"award-number":["81970598"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7202206"],"award-info":[{"award-number":["7202206"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022CR39"],"award-info":[{"award-number":["2022CR39"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2019-I2M-5-046"],"award-info":[{"award-number":["2019-I2M-5-046"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2023,1]]},"abstract":"\n Significance Statement<\/jats:title>\n \n Thinned glomerular basement membrane (tGBM) lesions, usually associated with\n COL4A3<\/jats:italic>\n \/\n COL4A4<\/jats:italic>\n \/\n COL4A5<\/jats:italic>\n gene variants, are not uncommon in sporadic IgA nephropathy (IgAN), but the underlying mechanism is unclear. Exome sequence analysis of 122 patients with sporadic IgAN with tGBM lesions (IgAN-tGBM) identified diagnostic\n COL4A3<\/jats:italic>\n \/\n COL4A4<\/jats:italic>\n \/\n COL4A5<\/jats:italic>\n gene variants in 38 patients (31.1%), with 37 different variants. Patients with IgAN-tGBM who did not have diagnostic variants showed more characteristics of IgAN, whereas those who did have diagnostic variants had higher proportions of GBM thickness <250 nm and milder glomerular injury. These findings suggest different mechanisms in patients with IgAN-tGBM with and without diagnostic variants in these collagen genes. The research indicated the importance of\n COL4A3<\/jats:italic>\n \/\n COL4A4<\/jats:italic>\n \/\n COL4A5<\/jats:italic>\n variant detection in patients with IgAN-tGBM.\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n Thinned glomerular basement membrane (tGBM) lesions are not uncommon in IgA nephropathy (IgAN). Type IV collagen\u2014built of\n \u03b1<\/jats:italic>\n 3,\n \u03b1<\/jats:italic>\n 4, and\n \u03b1<\/jats:italic>\n 5 chains, encoded by\n COL4A3<\/jats:italic>\n \/\n COL4A4<\/jats:italic>\n \/\n COL4A5<\/jats:italic>\n genes\u2014is the major component of glomerular basement membrane (GBM). In recent years, mutations in type IV collagen\u2013encoding genes were also reported in patients with a histologic diagnosis of FSGS. Pathogenic\n COL4A3<\/jats:italic>\n \/\n COL4A4<\/jats:italic>\n \/\n COL4A5<\/jats:italic>\n variants were recently identified in familial cases of IgAN, but the contribution of these variants to sporadic IgAN is still unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We compared 161 patients with sporadic IgAN with tGBM lesions (IgAN-tGBM) to matched patients with IgAN without tGBM lesions and matched patients with thin basement membrane nephropathy (TBMN). Variants of\n COL4A3<\/jats:italic>\n \/\n COL4A4<\/jats:italic>\n \/\n COL4A5<\/jats:italic>\n genes were screened and evaluated after whole-exome sequencing. GBM thickness was measured, and levels of circulating galactose-deficient IgA1 (Gd-IgA1) were assessed by ELISA.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The patients with IgAN-tGBM manifested milder disease than did patients with IgAN without tGBM but had more severe features than the patients with TBMN. Exome sequence analysis of the 122 patients with IgAN-tGBM identified 37 diagnostic variants of the\n COL4A3<\/jats:italic>\n \/\n COL4A4<\/jats:italic>\n \/\n COL4A5<\/jats:italic>\n genes among 38 patients (31.1%). Furthermore, patients with IgAN-tGBM who had diagnostic variants had higher proportions of GBM thickness <250 nm and milder glomerular injury, whereas patients with IgAN-tGBM who did not have diagnostic variants showed more characteristic features of IgAN, including higher intensity of glomerular IgA deposits and elevated Gd-IgA1 levels. These findings suggest different mechanisms in patients with versus without diagnostic variants of these collagen genes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n COL4A3<\/jats:italic>\n \/\n COL4A4<\/jats:italic>\n \/\n COL4A5<\/jats:italic>\n variant detection is essential in evaluating patients with sporadic IgAN with tGBM lesions.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2021111447","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T14:05:28Z","timestamp":1663769128000},"page":"132-144","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":44,"title":["Genetic Variants of the COL4A3, COL4A4, and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy Patients"],"prefix":"10.1681","volume":"34","author":[{"given":"Xiaohan","family":"Yuan","sequence":"first","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Key Laboratory of Renal Disease (Peking University), National Health Commission, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of Immuno-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Su","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Key Laboratory of Renal Disease (Peking University), National Health Commission, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of Immuno-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sufang","family":"Shi","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Key Laboratory of Renal Disease (Peking University), National Health Commission, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of Immuno-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2803-6956","authenticated-orcid":false,"given":"Lijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Key Laboratory of Renal Disease (Peking University), National Health Commission, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, China"},{"name":"Research Units of Diagnosis and Treatment of Immuno-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jicheng","family":"Lv","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China"},{"name":"Key Laboratory of Renal Disease (Peking University), National Health Commission, Beijing, 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