Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalPediatric Nephrology
Volume32
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

Fingerprint

Pediatrics
Nephrotic Syndrome
Mutation
Steroids
Disorders of Sex Development
Missense Mutation
Karyotype
Gonadoblastoma
Kidney
Wilms Tumor
Genetic Testing
Hernia
Chronic Kidney Failure
Genotype
Phenotype
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

Ahn, Y. H., Park, E. J., Kang, H. G., Kim, S. H., Cho, H. Y., Shin, J., ... Cheong, H. I. (2017). Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy. Pediatric Nephrology, 32(1), 81-89. https://doi.org/10.1007/s00467-016-3395-4
Ahn, Yo Han ; Park, Eu Jin ; Kang, Hee Gyung ; Kim, Seong Heon ; Cho, Hee Yeon ; Shin, Jaeil ; Lee, Joo Hoon ; Park, Young Seo ; Kim, Kyo Sun ; Ha, Il Soo ; Cheong, Hae Il. / Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy. In: Pediatric Nephrology. 2017 ; Vol. 32, No. 1. pp. 81-89.
@article{0aec1ed9ecd34e539396660943e331ba,
title = "Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy",
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.",
author = "Ahn, {Yo Han} and Park, {Eu Jin} and Kang, {Hee Gyung} and Kim, {Seong Heon} and Cho, {Hee Yeon} and Jaeil Shin and Lee, {Joo Hoon} and Park, {Young Seo} and Kim, {Kyo Sun} and Ha, {Il Soo} and Cheong, {Hae Il}",
year = "2017",
month = "1",
day = "1",
doi = "10.1007/s00467-016-3395-4",
language = "English",
volume = "32",
pages = "81--89",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",
number = "1",

}

Ahn, YH, Park, EJ, Kang, HG, Kim, SH, Cho, HY, Shin, J, Lee, JH, Park, YS, Kim, KS, Ha, IS & Cheong, HI 2017, 'Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy', Pediatric Nephrology, vol. 32, no. 1, pp. 81-89. https://doi.org/10.1007/s00467-016-3395-4

Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy. / Ahn, Yo Han; Park, Eu Jin; Kang, Hee Gyung; Kim, Seong Heon; Cho, Hee Yeon; Shin, Jaeil; Lee, Joo Hoon; Park, Young Seo; Kim, Kyo Sun; Ha, Il Soo; Cheong, Hae Il.

In: Pediatric Nephrology, Vol. 32, No. 1, 01.01.2017, p. 81-89.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy

AU - Ahn, Yo Han

AU - Park, Eu Jin

AU - Kang, Hee Gyung

AU - Kim, Seong Heon

AU - Cho, Hee Yeon

AU - Shin, Jaeil

AU - Lee, Joo Hoon

AU - Park, Young Seo

AU - Kim, Kyo Sun

AU - Ha, Il Soo

AU - Cheong, Hae Il

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84974829711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84974829711&partnerID=8YFLogxK

U2 - 10.1007/s00467-016-3395-4

DO - 10.1007/s00467-016-3395-4

M3 - Article

VL - 32

SP - 81

EP - 89

JO - Pediatric Nephrology

JF - Pediatric Nephrology

SN - 0931-041X

IS - 1

ER -