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

• Main Authors: Cai, J. (Author), Guan, Z. (Author), He, M. (Author), Jin, H. (Author), Li, L. (Author), Mao, J. (Author), Shu, Q. (Author), Wang, F. (Author), Wang, J. (Author), Zhao, M. (Author), Zhu, K. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: 46; abdominal mass; abdominal radiography; albumin; albumin blood level; amino acid sequence; Amino Acid Sequence; antineoplastic agent; Article; Asian continental ancestry group; Asian Continental Ancestry Group; B scan; Base Sequence; CA 19-9 antigen; carcinoembryonic antigen; carcinogenesis; case report; Cell Line, Tumor; cell viability; chemistry; child; China; Chinese; clinical article; clinical examination; clitoris hypertrophy; complementary DNA; computer assisted tomography; computer simulation; Computer Simulation; contrast enhancement; Denys Drash syndrome; Denys-Drash Syndrome; Denys-Drash syndrome (DDS); diagnostic imaging; disease severity; DNA extraction; DNA sequence; electrocardiogram; enalapril maleate; exon; female; Female; follow up; Follow-Up Studies; genetic screening; genetics; genomic DNA; heterozygosity; high throughput sequencing; histopathology; human; human tissue; Humans; hypertension; image analysis; indel mutation; infant; Infant; karyotype; kidney biopsy; kidney disease; laboratory test; laparoscopy; Laparoscopy; large core needle biopsy; microalbuminuria; missense mutation; mutation; Mutation; nephrectomy; nephroblastoma; nephrotic syndrome; nucleotide sequence; pedigree; Pedigree; physical examination; preschool child; RNA extraction; Sanger sequencing; sequence alignment; single nucleotide polymorphism; Tomography, X-Ray Computed; tumor cell line; valsartan; Wilms tumor; Wilms Tumor; Wilms tumor-1 (WT1); WT1 gene; WT1 protein; WT1 protein, human; WT1 Proteins; x-ray computed tomography; XY karyotype
• Online Access: View Fulltext in Publisher

 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. © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC