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Pediatric Nephrology
Published in: Pediatric Nephrology 1/2017

01-01-2017 | Original Article

Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy

Authors: Yo Han Ahn, Eu Jin Park, Hee Gyung Kang, Seong Heon Kim, Hee Yeon Cho, Jae Il Shin, Joo Hoon Lee, Young Seo Park, Kyo Sun Kim, Il-Soo Ha, Hae Il Cheong

Published in: Pediatric Nephrology | Issue 1/2017

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Abstract

Background

WT1 is one of the genes commonly reported as mutated in children with steroid-resistant nephrotic syndrome (SRNS). We analyzed genotype–phenotype correlations in pediatric SRNS patients with WT1 mutations.

Methods

From 2001 to 2015, WT1 mutations were detected in 21 out of 354 children with SRNS by genetic screening (5.9 %). The patients were grouped into missense (n = 11) and KTS splicing (n = 10) mutation groups.

Results

Nine (82 %) patients with missense mutations presented with congenital/infantile nephrotic syndrome, while 8 (80 %) with KTS splicing mutations presented with childhood-onset SRNS. Progression to end-stage renal disease (ESRD) was noted in all patients with missense mutations (median age, 2.6 months; interquartile range [IQR], 0.8 months to 1.7 years) and in 5 patients with KTS splicing mutations (median, 9.3 years; IQR, 3.3–16.5 years). Disorders of sexual development (DSDs) were noted in all 12 patients with a 46, XY karyotype and in only 1 of the 8 patients with a 46, XX karyotype. One patient developed a Wilms tumor and another developed gonadoblastoma. Three patients had a diaphragmatic defect or hernia.

Conclusions

WT1 mutations manifest as a wide spectrum of renal and extra-renal phenotypes. Genetic diagnosis is essential for overall management and to predict the genotype-specific risk of DSDs and the development of malignancies.
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Metadata
Title
Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy
Authors
Yo Han Ahn
Eu Jin Park
Hee Gyung Kang
Seong Heon Kim
Hee Yeon Cho
Jae Il Shin
Joo Hoon Lee
Young Seo Park
Kyo Sun Kim
Il-Soo Ha
Hae Il Cheong
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 1/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-016-3395-4

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