Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2022 Mar 21;35(6):837-843.
doi: 10.1515/jpem-2021-0673. Print 2022 Jun 27.

Bilateral Wilms' tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region

Mara Sanches Guaragna  1   2 , Felipe Lourenço Ledesma  3 , Victoria Zavanelli Manzano  4 , Andréa Trevas Maciel-Guerra  2   5 , Gil Guerra-Júnior  2   6 , Marcelo Milone Silva  7 , Pedro Luiz de Brito  7 , Maricilda Palandi de Mello  1   2
Affiliations
Case Reports

Bilateral Wilms' tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region

Mara Sanches Guaragna et al. J Pediatr Endocrinol Metab. .

Abstract

Objectives: Wilm's Tumor (WT) is the most common pediatric kidney cancer. Whereas most WTs are isolated, approximately 5% are associated with syndromes such as Denys-Drash (DDS), characterized by early onset nephropathy, disorders of sex development and predisposition to WT.

Case presentation: A 46,XY patient presenting with bilateral WT and genital ambiguity without nephropathy was heterozygous for the novel c.851_854dup variant in WT1 gene sequence. This variant affects the protein generating the frameshift p.(Ser285Argfs*14) that disrupts a nuclear localization signal (NLS) region.

Conclusions: This molecular finding is compatible with the severe scenario regarding the Wilm's tumor presented by the patient even though nephropathy was absent.

Keywords: Denys-Drash syndrome; WT1 nuclear localization signal; bilateral Wilms tumor.

PubMed Disclaimer

References

    1. Stiller, CA, Olshan, AF. Epidemiology of renal tumors of childhood. In: Kathy Pritchard-Jones JD, editor. Renal tumors of childhood. Washington, District of Columbia, USA: Springer US; 2014:1–17 pp.
    1. Barbaux, S, Niaudet, P, Gubler, MC, Grünfeld, JP, Jaubert, F, Kuttenn, F, et al.. Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 1997;17:467–70. https://doi.org/10.1038/ng1297-467.
    1. Bruening, W, Bardeesy, N, Silverman, BL, Cohn, RA, Machin, GA, Aronson, AJ, et al.. Germline intronic and exonic mutations in the Wilms’ tumour gene (WT1) affecting urogenital development. Nat Genet 1992;1:144–8. https://doi.org/10.1038/ng0592-144.
    1. Pelletier, J, Bruening, W, Kashtan, CE, Mauer, SM, Manivel, JC, Striegel, JE, et al.. Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 1991;67:437–47. https://doi.org/10.1016/0092-8674(91)90194-4.
    1. Scott, RH, Stiller, CA, Walker, L, Rahman, N. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet 2006;43:705–15. https://doi.org/10.1136/jmg.2006.041723.

Publication types

LinkOut - more resources