A novel WT1 gene mutation in a chinese girl with denys‐drash syndrome

OBJECTIVE: Denys‐Drash syndrome (DDS) is defined by the triad of Wilms tumor, nephrotic syndrome, and/or ambiguous genitalia. Genetic testing may help identify new gene mutation sites and play an important role in clinical decision‐making. METHODS: We present a patient with an XY karyotype and female appearance, nephropathy, and Wilms tumor in the right kidney. Genomic DNA was extracted from peripheral blood cells according to standard protocols. “Next‐generation” sequencing (NGS) was performed to identify novel variants. The variant was analyzed with Mutation Taster, and its function was explored by a cell growth inhibition assay. RESULTS: We found the first case of Denys‐Drash syndrome with the uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene. In silico analysis, the variant was predicted “disease‐causing” by Mutation Taster. The mutated variant showed a weaker effect in inhibiting tumor cells than wild‐type WT1. CONCLUSIONS: The uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene may be a crucial marker in DDS.