Abstract
Background
Nucleoporin nephropathy, a rare genetic kidney disorder, is not well-characterized despite its early onset in childhood.
Method
We analyzed the clinical and genetic data of pediatric patients diagnosed with nucleoporin nephropathy at a southern Chinese pediatric nephrology center, and reviewed global cases reported up until July 2024.
Results
In our center, five pediatric patients (aged 10 months to 8 years) were diagnosed with nucleoporin nephropathy. Three presented with steroid-resistant nephrotic syndrome, and one had initial extrarenal symptoms. All patients progressed to end-stage kidney disease. Global data shows 111 cases of nucleoporin nephropathy; 76.6% of patients initially presented with nephrotic syndrome, unresponsive to steroids or immunosuppressive therapy. 89.4% progressed to end-stage kidney disease in adolescence. Among the 37 transplant recipients, only 2 had proteinuria recurrence. Neurological symptoms were observed in a significant portion of patients, with variation across genotypes. East Asian patients, who account for 40.4% of the cases, often exhibit compound heterozygous missense, early renal involvement, and fewer extrarenal symptoms.
Conclusion
Routine nucleoporin gene testing is advised for Asian children with steroid-resistant nephrotic syndrome or end-stage kidney disease to prevent unnecessary treatments. While kidney transplantation has a favorable outlook, managing extrarenal symptoms of nucleoporin pehropathy is challenging.
Impact
-
Explore the link between nucleoporin gene mutations and disease phenotypes for a new understanding of NUP nephropathy.
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The renal phenotypes associated with NUP mutations display a remarkably consistent pattern as early-onset SRNS and progression to ESKD in adolescence.
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Highlight the importance in finding and managing the extrarenal symptoms associated with nucleoporin nephropathy.
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Regional specificities in NUP gene mutations are becoming apparent, with East Asian patients often presenting compound heterozygous mutations, early onset, rapid progression to end-stage kidney disease, and fewer extrarenal symptoms.
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Emphasize the necessity of nucleoporin gene testing for Asian children to prevent ineffective treatments.
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Data availability
The data that support the findings of this study are available within the article and its supplementary materials. Additional data related to this research can be requested from the corresponding author upon reasonable request.
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Acknowledgements
We thanks the patients and their families for their participation. We thank Dr. Liulu Xie for her assistance collecting the patients’ clinical data. We also thank for the assistance provided from all the members in Pediatric Nephrology Center and Kidney Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University. This work was supported by The National Key Research and Development Program of China (2022YFC2705100, 2022YFC2705101), Guangdong Basic and Applied Basic Research Foundation (No. 2019A1515010694). The funding source helped to perform the literature search and patients’ follow up, but did not have any role in design, execution, analysis, interpretation, or writing of the report or the decision to submit this report for publication. The authors declare that they have no relevant financial interests.
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All authors contributed to the study conception and design. This subject was designed by X.J. and L.C. Data collection and literature review were performed by Y.P. and M.J.. Data analysis was re-checked by L.R. and Z.L. The first draft of the manuscript was written by Y.P. and all authors commented on previous versions of the manuscript. The corresponding authors had full access to all the study data and had final responsibility for the decision to submit.
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Pei, Y., Jiang, M., Zhilang, L. et al. Exploring genotype-phenotype correlation in nucleoporin nephropathy. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-03977-3
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DOI: https://doi.org/10.1038/s41390-025-03977-3
