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

Mara Sanches Guaragna; Felipe Lourenço Ledesma; Victoria Zavanelli Manzano; Andréa Trevas Maciel-Guerra; Gil Guerra-Júnior; Marcelo Milone Silva; Pedro Luiz de Brito; Maricilda Palandi de Mello

doi:10.1515/jpem-2021-0673

Article

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

Mara Sanches Guaragna , Felipe Lourenço Ledesma , Victoria Zavanelli Manzano , Andréa Trevas Maciel-Guerra , Gil Guerra-Júnior , Marcelo Milone Silva , Pedro Luiz de Brito and Maricilda Palandi de Mello

Published/Copyright: March 21, 2022

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 6

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

Corresponding author: Mara Sanches Guaragna, Center for Molecular Biology and Genetic Engineering – CBMEG, State University of Campinas, Av. Cândido Rondon, 400, CEP: 13083-875 Campinas, São Paulo, Brazil; and Interdisciplinary Group for the Study of Sex Determination and Differentiation – GIEDDS, State University of Campinas, São Paulo, Brazil, Phone: +55 19 3521-1091, E-mail: mara.guaragna@gmail.com

Funding source: Fundação de Amparo à Pesquisa do Estado de São Paulo

Award Identifier / Grant number: 2015/20502-6 to MPdeM

Research funding: This work was supported by grant from Fundação de Amparo à Pesquisa do Estado de São Paulo (2015/20502-6 to MPdeM).
Author contributions: MSG carried out the genetic studies and drafted the manuscript; FLL carried out the histological and immunochemical evaluation and reviewed the manuscript; VZM carried out the clinical studies; GGJ was responsible for the genital ambiguity and endocrine evaluation of the patient and reviewed the manuscript; ATMG was responsible for the genital ambiguity evaluation of the patient and reviewed the manuscript; MM coordinated the study, was responsible for the clinical evaluation and reviewed the manuscript; PLB coordinated the study, was responsible for the clinical evaluation and reviewed the manuscript; MPM coordinated the genetic studies and reviewed the manuscript.
Competing interest: The authors have no conflicts of interest to declare.
Informed consent: Written informed consent for the study was obtained from the patients and their parents.
Ethical approval: This study was carried out in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Medical Science Faculty of the State University of Campinas. Written informed consent for the study was obtained from the patients and their parents.
Data availability statement: Data regarding oligonucleotides, PCR reactions and Sanger sequencing results are available upon request. Reference sequence ENSG00000184937 deposited in the Ensembl database (https://www.ensembl.org/Homo_sapiens) and NM_024426.6 transcript was used for nomenclature.

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Received: 2021-11-07

Accepted: 2022-02-19

Published Online: 2022-03-21

Published in Print: 2022-06-27

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Articles in the same Issue

https://doi.org/10.1515/jpem-2021-0673

Keywords for this article

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