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Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy

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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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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).

Author information

Author notes

  1. Yo Han Ahn

    Present address: Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea

Authors and Affiliations

  1. Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea

    Yo Han Ahn, Eu Jin Park, Hee Gyung Kang, Il-Soo Ha & Hae Il Cheong

  2. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea

    Hee Gyung Kang & Hae Il Cheong

  3. Department of Pediatrics, Pusan National University Children’s Hospital, Yangsan, Korea

    Seong Heon Kim

  4. Department of Pediatrics, Samsung Medical Center, Seoul, Korea

    Hee Yeon Cho

  5. Department of Pediatrics, Yonsei University College of Medicine, Severance Children’s Hospital, Seoul, Korea

    Jae Il Shin

  6. Department of Pediatrics, Asan Medical Center, Seoul, Korea

    Joo Hoon Lee & Young Seo Park

  7. Department of Pediatrics, Konkuk University Hospital, Seoul, Korea

    Kyo Sun Kim

  8. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea

    Il-Soo Ha & Hae Il Cheong

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  1. Yo Han Ahn
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Corresponding author

Correspondence to Hae Il Cheong.

Ethics declarations

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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Ahn, Y.H., Park, E.J., Kang, H.G. et al. Genotype–phenotype analysis of pediatric patients with WT1 glomerulopathy. Pediatr Nephrol 32, 81–89 (2017). https://doi.org/10.1007/s00467-016-3395-4

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  • DOI: https://doi.org/10.1007/s00467-016-3395-4

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