{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:53:24Z","timestamp":1792799604409,"version":"4.5.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Osaka Medical Research Foundation for Intractable Disease","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"https:\/\/ror.org\/04meywz55","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,8]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>LAMA5<\/jats:italic>\n                    gene encodes laminin \u03b15, an indispensable component of glomerular basement membrane and other types of basement membrane. A homozygous pathological variant in\n                    <jats:italic>LAMA5<\/jats:italic>\n                    is known to cause a systemic developmental syndrome including glomerulopathy. However, the roles of heterozygous\n                    <jats:italic>LAMA5<\/jats:italic>\n                    gene variants in human renal and systemic diseases have remained unclear. We performed whole-exome sequencing analyses of a family with slowly progressive nephropathy associated with hereditary focal segmental glomerulosclerosis, and we identified what we believe to be a novel probable pathogenic variant of\n                    <jats:italic>LAMA5<\/jats:italic>\n                    , NP_005551.3:p.Val3687Met. In vitro analyses revealed cell type\u2013dependent changes in secretion of variant laminin \u03b15 laminin globular 4-5 (LG4-5) domain. Heterozygous and homozygous knockin mice with a corresponding variant of human\n                    <jats:italic>LAMA5<\/jats:italic>\n                    , p.Val3687Met, developed focal segmental glomerulosclerosis\u2013like pathology with reduced laminin \u03b15 and increased glomerular vinculin levels, which suggested that impaired cell adhesion may underlie this glomerulopathy. We also identified pulmonary defects such as bronchial deformity and alveolar dilation. Reexaminations of the family revealed phenotypes compatible with reduced laminin \u03b15 and increased vinculin levels in affected tissues. Thus, the heterozygous p.Val3687Met variant may cause a new syndromic nephropathy with focal segmental glomerulosclerosis through possibly defective secretion of laminin \u03b15. Enhanced vinculin may be a useful disease marker.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158378","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T12:01:12Z","timestamp":1664452872000},"source":"Crossref","is-referenced-by-count":7,"title":["A heterozygous LAMA5 variant may contribute to slowly progressive, vinculin-enhanced familial FSGS and pulmonary defects"],"prefix":"10.1172","volume":"7","author":[{"given":"Jun-Ya","family":"Kaimori","sequence":"first","affiliation":[{"name":"Department of Inter-Organ Communication Research in Kidney Diseases and"},{"name":"Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamato","family":"Kikkawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo, 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