{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:31:59Z","timestamp":1790620319366,"version":"4.1.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"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><jats:italic>The Wilms Tumour gene 1<\/jats:italic> (<jats:italic>WT1<\/jats:italic>, NM_024426.6) holds significant importance in the developmental processes of the kidneys and gonads. Herein, we report a case of nephrotic syndrome and differences of sex development in a patient with novel mutations in <jats:italic>WT1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The child, identified as female based on social gender, exhibited symptoms at 6 years of age and was diagnosed with steroid-resistant nephrotic syndrome (SRNS). Renal biopsy findings indicated focal segmental glomerulosclerosis. Whole-exome sequencing unveiled a novel variant, c.1447\u2009+\u20096(IVS9)T\u2009&amp;gt;\u2009C, in the <jats:italic>WT1<\/jats:italic> gene, and karyotypic analysis revealed 46, XY, aligning with the phenotypic presentation of Frasier syndrome (FS, OMIM#136680) associated with <jats:italic>WT1<\/jats:italic> gene mutation. The influence of gene variants on mRNA splicing was examined using <jats:italic>in vitro<\/jats:italic> minigene assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The variant was classified as likely pathogenic (PS2\u2009+\u2009PM2_Supporting\u2009+\u2009PP3) in accordance with American College of Medical Genetics and Genomics (ACMG) guidelines. <jats:italic>in vitro<\/jats:italic> minigene experiments demonstrated that the c.1447\u2009+\u20096(IVS9)T\u2009&amp;gt;\u2009C variant altered the splicing pattern of exon 9 in the <jats:italic>WT1<\/jats:italic> gene from two isoforms to a single form, thereby supporting its pathogenicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Through high-throughput sequencing and <jats:italic>in vitro<\/jats:italic> minigene splicing experiments, the c.1447\u2009+\u20096T\u2009&amp;gt;\u2009C variant in the <jats:italic>WT1<\/jats:italic> gene was supported as the underlying genetic cause in the child patient, thereby expanding the spectrum of gene variants of <jats:italic>WT1 gene<\/jats:italic> and enhancing our comprehension of the molecular pathogenesis of this disorder.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1657533","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T05:35:27Z","timestamp":1756964127000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel variant leads to WT1-related nephrotic syndrome and differences of sex development: a case 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