{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T02:30:02Z","timestamp":1786329002142,"version":"build-2736575974"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants in the transient receptor potential cation channel subfamily C member 6 (TRPC6) cause autosomal dominant focal segmental glomerulosclerosis (FSGS). We report a patient with early-onset FSGS carrying a novel\n                      <jats:italic>TRPC6<\/jats:italic>\n                      variant not previously described.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 21-year-old Chinese male presented with proteinuria (3.17g\/24h) and mild renal insufficiency (Cr 103\u00a0\u03bcmol\/L). Renal biopsy confirmed FSGS, not otherwise specified (NOS). Genetic testing was initially declined due to cost concerns. He received losartan, dapagliflozin, strict salt restriction, and ambrisentan, achieving proteinuria reduction to 0.7g\/24h without immunosuppression. Two years later, genetic testing identified a novel\n                      <jats:italic>TRPC6<\/jats:italic>\n                      variant: c.131C&amp;gt;T p.(Pro44Leu), extremely rare in public databases and classified as a variant of uncertain significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This is the first report of the\n                      <jats:italic>TRPC6<\/jats:italic>\n                      p.Pro44Leu variant, expanding the variant spectrum of\n                      <jats:italic>TRPC6<\/jats:italic>\n                      -associated FSGS. The clinical decision to withhold immunosuppression was guided primarily by the patient\u2019s phenotype (young age, sub-nephrotic proteinuria, FSGS-NOS, and no secondary causes); the\n                      <jats:italic>TRPC6<\/jats:italic>\n                      variant, although classified as a VUS, provided supportive evidence for a genetic etiology and reinforced this management approach. This case demonstrates that genetic testing can guide personalized management in young patients with FSGS, offering a practical framework for avoiding unnecessary treatment-related morbidity. This case also illustrates that cost and psychological barriers can delay genetic diagnosis and highlights the value of early supportive therapy in genetic FSGS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1913168","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T02:14:52Z","timestamp":1786328092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel TRPC6 variant (c.131C&gt;T, p.(Pro44Leu)) associated with focal segmental glomerulosclerosis: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijie","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guorong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beijing Luhe Hospital Affiliated to Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"156402","DOI":"10.1016\/j.prp.2026.156402","article-title":"Modulation of AKT\/GSK-3\u03b2 signaling by ambrisentan alleviates chronic kidney disease","volume":"270","author":"Bhadange","year":"2026","journal-title":"Pathol. 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