{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:23:39Z","timestamp":1782221019139,"version":"3.54.5"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Focal segmental glomerulosclerosis (FSGS) is a major cause of end stage kidney disease, with the collapsing form having the worst prognosis. Study of families with hereditary FSGS has provided insight into disease mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this report, we describe a sibling pair with <jats:italic>NUP93<\/jats:italic> mutations and collapsing FSGS (cFSGS). For each brother, we performed next generation sequencing and segregation analysis by direct sequencing. To determine if the variants found in the index family are a common cause of cFSGS, we screened 7 patients with cFSGS, gleaned from our cohort of 200 patients with FSGS, for variants in <jats:italic>NUP93<\/jats:italic> as well as for <jats:italic>APOL1<\/jats:italic> high-risk genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified segregating compound heterozygous <jats:italic>NUP93<\/jats:italic> variants <jats:italic>(1) c.1772G<\/jats:italic> &amp;gt; <jats:italic>T p.G591V, 2) c.2084T<\/jats:italic> &amp;gt; <jats:italic>C p.L695S)<\/jats:italic> in the two brothers. We did not find any pathogenic variants in the seven patients with cFSGS from our cohort, and as expected five of these seven patients carried the <jats:italic>APOL1<\/jats:italic> high-risk genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To the best of our knowledge, this is the first report of cFSGS in patients with <jats:italic>NUP93<\/jats:italic> mutations, based on this report, mutations in <jats:italic>NUP93<\/jats:italic> and other nucleoporin genes should be considered when evaluating a child with familial cFSGS. Determining the mechanisms by which these variants cause cFSGS may provide insight into the pathogenesis of the more common primary and virus-mediated forms of cFSGS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.915174","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T08:26:18Z","timestamp":1657182378000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations"],"prefix":"10.3389","volume":"10","author":[{"given":"Rachel K.","family":"Cason","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Chryst-Stangl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinsie","family":"Huggins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaye E.","family":"Brathwaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon M.","family":"Lane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry A.","family":"Greenbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivette D.","family":"D\u2019Agati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasheed A.","family":"Gbadegesin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-029249","article-title":"Incidence and relapse of idiopathic nephrotic syndrome: meta-analysis.","volume":"148","year":"2021","journal-title":"Pediatrics."},{"key":"B2","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/s0022-3476(81)80760-3","article-title":"The primary nephrotic syndrome in children. identification of patients with minimal change nephrotic syndrome from initial response to prednisone. 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