Wilms' tumor suppressor gene mutations in girls with sporadic isolated steroid-resistant nephrotic syndrome

Yang, Yuhui; Zhao, Fei; Feng, Dong-ning; Wang, J.J.; Wang, C.F.; Nie, Xiaojing; Xia, Guohua; Chen, G.M.; Yu, Zhongxin

doi:10.4238/2013.december.4.5

Cited by 10 publications

(13 citation statements)

References 27 publications

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“…Interestingly, one unusual FS case was reported with an IVS 9 + 4 C>T mutation, genotypically the case was a male and presented with diaphragmatic hernia, hypospadias and unilateral cryptorchidism23. According to the reports, WT1 mutation mostly occurred in SRNS girls71011121324. Early (pre-pubertal period) diagnosis may help in the management of FS and to offer a reliable prognosis11121922.…”

Section: Resultsmentioning

confidence: 99%

Wilms′ tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome

et al. 2016

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Background & objectives:Clinically, nephrotic syndrome (NS) is a diverse group of symptoms; about 20 per cent of NS cases are resistant to steroid treatment, and within ten years they progress to end-stage renal disease. The present study was undertaken to identify the mutations of Wilms’ tumour 1 (WT1) gene in steroid-resistant NS (SRNS) children.Methods:A total of 173 children with SRNS and 100 children in the control group were enrolled in the study. DNA extraction was done, screened for WT1 (exons 8 and 9) gene amplified by polymerase chain reaction and direct sequencing. Karyotype analyses were done for WT1 mutation cases.Results:WT1 mutations were found in three of 173 SRNS cases (2 girls, 1 boy). All of them had intron 9 (IVS 9 + 4 C>T, 2; IVS + 5 G>A, 1) mutation. Of these three cases, one had familial and another two had sporadic history. Renal histology analysis showed two cases with focal segmental glomerulosclerosis (FSGS) and they had external female genitalia but 46, XY karyotype. Both of them had streak gonads. Of the three cases, one expired.Interpretation & conclusions:The findings of the present study indicate that all females with SRNS-FSGS should be screened for WT1 gene mutation to diagnose whether they have FS for possible gonadectomy.

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Section: Resultsmentioning

confidence: 99%

Wilms′ tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome

et al. 2016

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“…Eight cases of type 3 Frasier syndrome have been reported (10,13,14,(31)(32)(33)(34)(35)(36). Few type 3 Frasier syndrome cases are diagnosed because patients exhibit normal secondary sexual characteristics by the XX chromosome and suffer from renal failure without gonadal impairment.…”

Section: Type 3 Frasier Syndrome (Female External Genitals With Sex Cmentioning

confidence: 99%

Gonadal Tumor in Frasier Syndrome: A Review and Classification

Ezaki

Hashimoto

Asano

et al. 2015

Cancer Prevention Research

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Frasier syndrome is a rare inherited disease characterized by steroid-resistant nephrotic syndrome, gonadal tumor, and male pseudohermaphroditism (female external genitalia with sex chromosomes XY), which is based on a splice site mutation of Wilms tumor-suppressor gene 1 (WT1). Several unusual Frasier syndrome cases have been reported in which male pseudohermaphroditism was absent. We reviewed 88 Frasier syndrome cases in the literature and classified them into three types (type 1–3) according to external genitalia and sex chromosomes, and described their clinical phenotypes. Type 1 Frasier syndrome is characterized by female external genitalia with 46,XY (n = 72); type 2 by male external genitalia with 46,XY (n = 8); and type 3 by female external genitalia with 46,XX (n = 8). Clinical course differs markedly among the types. Although type 1 is noticed at the mean age of 16 due to mainly primary amenorrhea, type 2 and 3 do not present delayed secondary sex characteristics, making diagnosis difficult. The prevalence of gonadal tumor is high in type 1 (67%) and also found in 3 of the 8 type 2 cases, but not in any type 3 cases, which emphasize that preventive gonadectomy is unnecessary in type 3. On the basis of our findings, we propose a new diagnostic algorithm for Frasier syndrome. Cancer Prev Res; 8(4); 271–6. ©2015 AACR.

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“…Recent studies have demonstrated that mutations in WT1 can lead to syndromic forms of steroid-resistant NS (SRNS), such as Denys-Drash or Frasier syndrome, and can cause isolated SRNS [8, 9]. Between 10% and 20% of patients fail to respond to steroid therapy; thus, the prognosis for SRNS is usually poor, due to the increased risk of developing end-stage renal disease [10, 11].…”

Section: Introductionmentioning

confidence: 99%

“…Beltcheva et al reported a case of a pediatric patient with SRNS that was caused by a novel dominant WT1 mutation, C11184A, identified in exon 9 [10]. Mutations within WT1 are frequent causes of sporadic, isolated cases of SRNS in girls [8]. WT1 expression is modulated by microRNAs (miRNAs) [12], which are small (20–25 nucleotides), noncoding RNA molecules that act as posttranscriptional regulators of gene expression in animals and plants, participating in many key biological processes [13].…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic Localization of WT1 and Decrease of miRNA-16-1 in Nephrotic Syndrome

Zapata‐Benavides

Arellano-Rodríguez

Bollain-y-Goytia

et al. 2017

BioMed Research International

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Nephrotic syndrome (NS) is a glomerular disease that is defined by the leakage of protein into the urine and is associated with hypoalbuminemia, hyperlipidemia, and edema. Steroid-resistant NS (SRNS) patients do not respond to treatment with corticosteroids and show decreased Wilms tumor 1 (WT1) expression in podocytes. Downregulation of WT1 has been shown to be affected by certain microRNAs (miRNAs). Twenty-one patients with idiopathic NS (68.75% were SSNS and 31.25% SRNS) and 10 healthy controls were enrolled in the study. Podocyte number and WT1 location were determined by immunofluorescence, and the serum levels of miR-15a, miR-16-1, and miR-193a were quantified by RT-qPCR. Low expression and delocalization of WT1 protein from the nucleus to the cytoplasm were found in kidney biopsies of patients with SRNS and both nuclear and cytoplasmic localization were found in steroid-sensitive NS (SSNS) patients. In sera from NS patients, low expression levels of miR-15a and miR-16-1 were found compared with healthy controls, but only the miR-16-1 expression levels showed statistically significant decrease (p = 0.019). The miR-193a expression levels only slightly increased in NS patients. We concluded that low expression and delocalization from the WT1 protein in NS patients contribute to loss of podocytes while modulation from WT1 protein is not associated with the miRNAs analyzed in sera from the patients.

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Wilms' tumor suppressor gene mutations in girls with sporadic isolated steroid-resistant nephrotic syndrome

Cited by 10 publications

References 27 publications

Wilms′ tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome

Wilms′ tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome

Gonadal Tumor in Frasier Syndrome: A Review and Classification

Cytoplasmic Localization of WT1 and Decrease of miRNA-16-1 in Nephrotic Syndrome

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