{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T01:07:57Z","timestamp":1784596077521,"version":"3.55.0"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI Grant","award":["20K07622"],"award-info":[{"award-number":["20K07622"]}]},{"name":"JSPS KAKENHI Grant","award":["20K08625"],"award-info":[{"award-number":["20K08625"]}]},{"name":"NIH","award":["R01DK078314"],"award-info":[{"award-number":["R01DK078314"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,22]]},"abstract":"<jats:p>\n                    Mutations in\n                    <jats:italic>LAMB2<\/jats:italic>\n                    , encoding laminin \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    , cause Pierson syndrome and occasionally milder nephropathy without extrarenal abnormalities. The most deleterious missense mutations that have been identified affect primarily the N-terminus of laminin \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    . On the other hand, those associated with isolated nephropathy are distributed across the entire molecule, and variants in the \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    LEa-LF-LEb domains are exclusively found in cases with isolated nephropathy. Here we report the clinical features of mild isolated nephropathy associated with 3\n                    <jats:italic>LAMB2<\/jats:italic>\n                    variants in the LEa-LF-LEb domains (p.R469Q, p.G699R, and p.R1078C) and their biochemical characterization. Although Pierson syndrome missense mutations often inhibit laminin \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    secretion, the 3 recombinant variants were secreted as efficiently as WT. However, the \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    variants lost pH dependency for heparin binding, resulting in aberrant binding under physiologic conditions. This suggests that the binding of laminin \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    to negatively charged molecules is involved in glomerular basement membrane (GBM) permselectivity. Moreover, the excessive binding of the \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    variants to other laminins appears to lead to their increased deposition in the GBM. Laminin \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    also serves as a potentially novel cell-adhesive ligand for integrin \u03b1\n                    <jats:sub>4<\/jats:sub>\n                    \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    . Our findings define biochemical functions of laminin \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    variants influencing glomerular filtration that may underlie the pathogenesis of isolated nephropathy caused by\n                    <jats:italic>LAMB2<\/jats:italic>\n                    abnormalities.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.145908","type":"journal-article","created":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T14:01:06Z","timestamp":1616335266000},"source":"Crossref","is-referenced-by-count":13,"title":["Laminin \u03b22 variants associated with isolated nephropathy that impact matrix regulation"],"prefix":"10.1172","volume":"6","author":[{"given":"Yamato","family":"Kikkawa","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeko","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan."},{"name":"Department of Pediatric Nephrology, School of Medicine, Tokyo Women\u2019s Medical University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Urae","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Tokyo 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Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyoshi","family":"Nomizu","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4533-0412","authenticated-orcid":true,"given":"Helen","family":"Liapis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Hisano","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Chiba Children\u2019s Hospital, Chiba, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Akioka","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, School of 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