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Pediatric Nephrology

, Volume 32, Issue 1, pp 81–89 | Cite as

Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy

  • 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 CheongEmail author
Original Article

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.

Keywords

WT1 gene Steroid-resistant nephrotic syndrome Disorder of sexual development Malignancy Diaphragmatic defect 

Notes

Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C0014).

Compliance with ethical standards

This study was approved by the Seoul National University Hospital’s Institutional Review Board. Informed consent was obtained from all individual participants included in this study or their parents.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© IPNA 2016

Authors and Affiliations

  • Yo Han Ahn
    • 1
    • 2
  • Eu Jin Park
    • 1
  • Hee Gyung Kang
    • 1
    • 3
  • Seong Heon Kim
    • 4
  • Hee Yeon Cho
    • 5
  • Jae Il Shin
    • 6
  • Joo Hoon Lee
    • 7
  • Young Seo Park
    • 7
  • Kyo Sun Kim
    • 8
  • Il-Soo Ha
    • 1
    • 9
  • Hae Il Cheong
    • 1
    • 3
    • 9
    Email author
  1. 1.Department of PediatricsSeoul National University Children’s HospitalSeoulKorea
  2. 2.Hallym University Kangnam Sacred Heart HospitalSeoulKorea
  3. 3.Research Coordination Center for Rare DiseasesSeoul National University HospitalSeoulKorea
  4. 4.Department of PediatricsPusan National University Children’s HospitalYangsanKorea
  5. 5.Department of PediatricsSamsung Medical CenterSeoulKorea
  6. 6.Department of Pediatrics, Yonsei University College of MedicineSeverance Children’s HospitalSeoulKorea
  7. 7.Department of PediatricsAsan Medical CenterSeoulKorea
  8. 8.Department of PediatricsKonkuk University HospitalSeoulKorea
  9. 9.Kidney Research Institute, Medical Research CenterSeoul National University College of MedicineSeoulKorea

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