{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:47:42Z","timestamp":1789984062029,"version":"4.0.1"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>\n                    Steroid\u2013resistant nephrotic syndrome (SRNS), a heterogeneous disorder of the renal glomerular filtration barrier, results in impairment of glomerular permselectivity. Inheritance of genetic SRNS may be autosomal dominant or recessive, with a subset of autosomal recessive SRNS presenting as congenital nephrotic syndrome (CNS). Mutations in 53 genes are associated with human SRNS, but these mutations explain \u226430% of patients with hereditary cases and only 20% of patients with sporadic cases. The proteins encoded by these genes are expressed in podocytes, and malfunction of these proteins leads to a universal end point of podocyte injury, glomerular filtration barrier disruption, and SRNS. Here, we identified novel disease\u2013causing mutations in\n                    <jats:italic toggle=\"yes\">membrane\u2013associated guanylate kinase, WW, and PDZ domain\u2013containing 2<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">MAGI2<\/jats:italic>\n                    ) through whole-exome sequencing of a deeply phenotyped cohort of patients with congenital, childhood\u2013onset SRNS. Although\n                    <jats:italic toggle=\"yes\">MAGI2<\/jats:italic>\n                    has been shown to interact with nephrin and regulate podocyte cytoskeleton and slit diaphragm dynamics,\n                    <jats:italic toggle=\"yes\">MAGI2<\/jats:italic>\n                    mutations have not been described in human SRNS. We detected two unique frameshift mutations and one duplication in three patients (two families); two siblings shared the same homozygous frameshift mutation, whereas one individual with sporadic SRNS exhibited compound heterozygosity. Two mutations were predicted to introduce premature stop codons, and one was predicted to result in read through of the normal translational termination codon. Immunohistochemistry in kidney sections from these patients revealed that mutations resulted in lack of or diminished podocyte MAGI2 expression. Our data support the finding that mutations in the\n                    <jats:italic toggle=\"yes\">MAGI2<\/jats:italic>\n                    gene are causal for congenital SRNS.\n                  <\/jats:p>","DOI":"10.1681\/asn.2016040387","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T22:10:29Z","timestamp":1481235029000},"page":"1614-1621","source":"Crossref","is-referenced-by-count":80,"title":["MAGI2 Mutations Cause Congenital Nephrotic Syndrome"],"prefix":"10.1681","volume":"28","author":[{"given":"Agnieszka","family":"Bierzynska","sequence":"first","affiliation":[{"name":"Bristol Renal and Children\u2019s Renal Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Soderquest","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology and Mucosal Biology, Department of Experimental Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Dean","sequence":"additional","affiliation":[{"name":"Bristol Genetics Laboratory, North Bristol National Health Service Trust, Bristol, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Colby","sequence":"additional","affiliation":[{"name":"Bristol Renal and Children\u2019s Renal Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Rollason","sequence":"additional","affiliation":[{"name":"Bristol Renal and Children\u2019s Renal Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Jones","sequence":"additional","affiliation":[{"name":"Alder Hey Children\u2019s Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol D.","family":"Inward","sequence":"additional","affiliation":[{"name":"Bristol Renal and Children\u2019s Renal Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh J.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Bristol Renal and Children\u2019s Renal Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, King\u2019s College London, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham M.","family":"Lord","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology and Mucosal Biology, Department of Experimental Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Williams","sequence":"additional","affiliation":[{"name":"Bristol Genetics Laboratory, North Bristol National Health Service Trust, Bristol, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin I.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Bristol Renal and Children\u2019s Renal Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ania B.","family":"Koziell","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology and Mucosal Biology, Department of Experimental Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moin A.","family":"Saleem","sequence":"additional","affiliation":[{"name":"Bristol Renal and Children\u2019s Renal Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of NephroS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the UK study of Nephrotic Syndrome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,12,8]]},"reference":[{"key":"B1-20230829","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2215\/CJN.07200712","article-title":"Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome.","volume":"8","author":"McCarthy","year":"2013","journal-title":"Clin J Am Soc Nephrol"},{"key":"B2-20230829","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1681\/ASN.2014050489","article-title":"A single-gene cause in 29.5% of cases of steroid-resistant nephrotic 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