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Pediatric Oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Stephen Lowis, Rachel Cox, John Moppett, Helen Rees
The incidence of Wilms’ tumor (WT) is 8.1 cases per million Caucasian children less than 15 years of age, usually presenting before age 5 years. It is associated with congenital abnormalities such as isolated aniridia, isolated hemihypertrophy (prevalence 2.5% of children with Wilms’ tumor), and genitourinary anomalies (hypospadias, undescended testis—about 6%). WT is also linked to genetic (overgrowth and non-overgrowth) syndromes including Perlman syndrome, Beckwith–Weidemann (1% of children with WT), and WAGR syndrome (hemihypertrophy, aniridia, genitourinary malformation, and mental retardation). Denys–Drash syndrome is associated with mutations in the WT1 gene.
Pediatrie genitourinary oncology
Published in J Kellogg Parsons, E James Wright, The Brady Urology Manual, 2019
Jennifer Miles-Thomas, Matthew E Nielsen, Caleb P Nelson
Denys-Drash syndrome: Associated with an 11p13 mutationAssociated abnormalities include male pseudohermaphroditism, renal mesangial sclerosis, nephroblastoma, and end-stage renal disease.
Paediatric oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Stephen Lowis, Rachel Cox, John Moppett, Antony Ng
At least three genes are associated with WT and because the incidence of familial WT is less than 1%, the genetics of WT do not always follow the simple two-hit model of tumour suppressor genes.243 Patients with the WAGR syndrome have a constitutional deletion of the WT suppressor gene, WT1, which is located at 11p13.243 Although constitutional mutations of WT1 are described for children with the rare Denys–Drash syndrome, specific mutations of WT1 have been found in less than 10% sporadic WT.244WT2 has been found to map to 11p15.5, which is also the location of the Beckwith–Weidemann gene abnormality, and familial WT genes are also located at 17q12 and 7p13.241
Confirmation of Xp22.11 Duplication as a Germline Susceptibility Alteration in a Wilms Tumor Arising in Horseshoe Kidney
Published in Fetal and Pediatric Pathology, 2022
Hui-fang Zhou, Ina E. Amarillo, Stacy Snyder, Jorge L. Granadillo, Christopher J. O’Conor, Patrick Dillon, David Wilson, Frederick S. Huang, Louis P. Dehner, Mai He
Wilms tumor is associated with WT1 pathogenic variants or epigenetic defects at 11p15. Approximately 10% of Wilms tumor are associated with germline alterations which were summarized by Dome et al. [2] Syndromes associated with Wilms tumor include WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability) due to 11p13 deletion, Denys-Drash syndrome (46,XY disorders of sex development, gonadal dysgenesis, glomerulosclerosis and Wilms tumor) with WT1 dominant negative missense variation, and Beckwith-Wiedemann syndrome (macrosomia, macroglossia, abdominal wall defects, an increased risk for childhood tumors, and kidney abnormalities) with 11p15.5 abnormalities. Other genetic abnormalities include FWT1 (17q12-12.1) and FWT2 (19q13) variations described in familial WT [4], and inactivating variations of WTX (Xq11.1) [5]. Somatically acquired variants in WTX (also known as AMER1), for which germline pathogenic variants cause osteopathia striata with cranial sclerosis (OSCS), are found in the neoplastic tissue of 15-30% of patients with Wilms tumor [6]. Additionally, sequence or copy number variations of TP53 have been implicated as an important event in the development of diffuse anaplastic Wilms tumor and patients with stage III/IV TP53-variant diffuse anaplastic Wilms tumors have significantly higher relapse and death rates than their TP53 wild-type counter parts [7].
Application of miR-193a/WT1/PODXL axis to estimate risk and prognosis of idiopathic membranous nephropathy
Published in Renal Failure, 2019
What’s more, two podocytes located downstream of miR-193 (i.e., WT1 and PODXL) were also nephropathy-relevant [30]. For one thing, mutation of WT1 could induce idiopathic diffuse mesangial sclerosis and Denys-Drash syndrome [31], and depression of WT1 expression tended to trigger onset of crescentic nephritis and mesangial sclerosis [16]. For another, patients with FSGS, minimal lesions, diabetic nephropathy, and IgA nephropathy were discovered with a reduction in the glomerular expression of PODXL [32]. Besides the renal disorders, our investigation further proposed down-regulated expressions of WT1 and PODXL as desirable indicators for incremental risk (Supplementary Figures 1–4 and Supplementary Tables 1–2) and unfavorable prognosis (i.e., renal survival) of IMN (Figure 3 and Table 3). As a matter of fact, the roles of WT1 and PODXL in altering the structure of podocytes could, to some degree, explain the clinical association of WT1/PODXL with IMN onset [33]. To be specific, WT1-interacting protein (i.e., WTIP) possibly led to dysregulated phenotypes of podocytes by hindering expressions of WT1-dependent genes [34]. Furthermore, the proper functioning of PODXL not merely ensured the integrity of negative-charge barrier in the glomerular filtration membrane, but also could maintain the normal slit diaphragm between foot processes [35]. From the above, WT1 and PODXL could participate in certain IMN-related mechanisms that miR-193a was not involved with, which might account for why miRNA-193a combined with WT1 and PODXL produced higher accuracies in assessing IMN onset and prognosis than miRNA-193a alone (Figure 4 and Table 5).
Focal Segmental Membranoproliferative Glomerulonephritis: A Histological Variant of Denys-Drash Syndrome.
Published in Fetal and Pediatric Pathology, 2021
A. B. Karmila, Y. C. Yap, M. Appadurai, L. Oh, M. Fazarina, F. Abd Ghani, H. Ariffin
The classical triad of nephropathy, pseudohermaphroditism and Wilms’ Tumor (WT) is known as Denys-Drash Syndrome (DDS) (OMIM 194080) and results from mutations in exon 8 or 9 of the WT1 gene. A similar condition, described as Frasier Syndrome (FS) (OMIM 136680), is due to a mutation in intron 9 of WT1. FS consists of XY females with gonadal dysgenesis and glomerulopathy. The prevalence of DDS is unknown but 150 cases have been described thus far.