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Mutational analysis of NPHS2 and WT1 in frequently relapsing and steroid-dependent nephrotic syndrome

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Abstract

Idiopathic nephrotic syndrome is a common pediatric kidney disease, 80% of all cases are steroid sensitive (SSNS). A significant proportion of children with SSNS will have a frequently relapsing or steroid-dependent course (FRNS/SDNS) that is associated with significant treatment-related morbidity. Mutations in NPHS2 account for more than 28% of all cases of steroid-resistant nephrotic syndrome (SRNS) and dominant mutations in WT1 for 5%; while mutations are absent from children with uncomplicated SSNS. Since FRNS/SDNS is phenotypically positioned within a spectrum between SSNS and SRNS, we hypothesized that heterozygous mutations of NPHS2 may be causing FRNS/SDNS. Mutational analysis of NPHS2 and WT1 was carried out in a single-center cohort of 20 children with FRNS/SDNS, ten children with uncomplicated SSNS (control), and 22 children with SRNS (control). Renal biopsy findings were available in 15/20 children with FRNS/SDNS and revealed IgM nephropathy, MCNS, and FSGS in six, five, and four children, respectively. Children with FRNS/SDNS were significantly younger at first presentation than those with SSNS and SRNS (median age: 3.0 years in FRNS/SDNS patients, 7.0 years in SSNS patients, and 5.0 in SRNS patients; p < 0.001). No NPHS2 or WT1 mutations were found in patients with FRNS/SDNS and uncomplicated SSNS. The hypothesis that FRNS/SDNS may be associated with heterozygous mutations in NPHS2 or WT1 was not confirmed.

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Acknowledgements

We would like to thank the patients and their parents for their participation in this study. We would also like to thank Drs. D. Kershaw, P. Brophy, J. Lin, W. Smoyer, and S. Thomas for allowing us to study their patients. We also thank Dr. B. Hoskins for proof reading the manuscript. F.H. is supported by grants from the NIH (P50-DK039255), the Smokler Foundation and the Thrasher Research Foundation.

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Authors and Affiliations

  1. Department of Pediatrics Division of Nephrology, Ann Arbor, MI, 48109, USA

    Rasheed Gbadegesin, Bernward Hinkes, Christopher Vlangos, Bettina Mucha, Jinhong Liu, Jeff Hopcian & Friedhelm Hildebrandt

  2. Human Genetics, University of Michigan, Ann Arbor, MI, 48109, USA

    Friedhelm Hildebrandt

  3. University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-0646, USA

    Friedhelm Hildebrandt

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  1. Rasheed Gbadegesin
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  2. Bernward Hinkes
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  3. Christopher Vlangos
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  4. Bettina Mucha
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  5. Jinhong Liu
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  6. Jeff Hopcian
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  7. Friedhelm Hildebrandt
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Correspondence to Friedhelm Hildebrandt.

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Gbadegesin, R., Hinkes, B., Vlangos, C. et al. Mutational analysis of NPHS2 and WT1 in frequently relapsing and steroid-dependent nephrotic syndrome. Pediatr Nephrol 22, 509–513 (2007). https://doi.org/10.1007/s00467-006-0377-y

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  • DOI: https://doi.org/10.1007/s00467-006-0377-y

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