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NPHS2 p.V290M mutation in late-onset steroid-resistant nephrotic syndrome

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Abstract

Background

The most frequently mutated gene of steroid-resistant nephrotic syndrome (SRNS) is NPHS2. Current guidelines propose the sequencing of all NPHS2 exons only in childhood-onset SRNS.

Methods

A cohort of 38 Hungarian patients with childhood-onset nephrotic-range proteinuria was screened for NPHS2 mutations. The frequency of the p.V290M mutation in late-onset SRNS was examined in the French and PodoNet cohorts.

Results

Of the 38 Hungarian patients screened, seven carried NPHS2 mutations on both alleles, of whom two—diagnosed with proteinuria through school screening programs at the age of 9.7 and 14 years, respectively—did not develop nephrotic syndrome in childhood. The first, an 18-year-old boy, homozygous for p.V290M, has never developed edema. The second, a 31-year-old woman—compound heterozygous for p.V290M and p.R138Q—was first detected with hypoalbuminemia (<30 g/l) and edema at the age of 24.3 and 27.5 years, respectively. Both patients currently have a normal glomerular filtration rate. The mutation p.V290M was carried by three of the 38 patients in the Hungarian cohort, by two of the 95 patients with late-onset SRNS in the PodoNet cohort and by none of the 83 patients in the French cohort.

Conclusions

We propose that not only the p.R229Q variant, but also the p.V290M mutation should be screened in Central and Eastern European patients with late-onset SRNS.

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Acknowledgments

This work was supported by Pfizer, TÁMOP-4.2.1/B-09/1/KMR-2010-0001, OTKA 84087/2010, Bólyai János research fellowship of the Hungarian Academy of Sciences and Magyary Zoltán fellowship for KT. The authors thank Mária Bernáth for expert technical assistance.

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Authors and Affiliations

  1. First Department of Pediatrics, Semmelweis University, Budapest, Bókay J. u. 53, Budapest, 1083, Hungary

    Andrea Kerti, Rózsa Csohány, Attila Szabó, Péter Sallay, George Reusz, Tivadar Tulassay & Kálmán Tory

  2. Nephrology Outpatient Department, FMC Szépvölgyi Dialysis Centre, Szent János Hospital, Budapest, Hungary

    Ottó Árkossy

  3. INSERM U983, Hôpital Necker, Paris, France

    Vincent Moriniére & Corinne Antignac

  4. Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, MI, USA

    Virginia Vega-Warner

  5. Clinical and Research Center for Molecular Neurology, Semmelweis University, Budapest, Hungary

    Gábor Nyírő

  6. Department of Pediatrics, University of Pécs, Pécs, Hungary

    Orsolya Lakatos

  7. Medical and Health Science Center, Pediatric Institute, University of Debrecen, Debrecen, Hungary

    Tamás Szabó

  8. Department of Biology and Genetics, Medical University of Gdansk, Gdansk, Poland

    Beata S. Lipska

  9. Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany

    Beata S. Lipska & Franz Schaefer

  10. Research Laboratory for Pediatrics and Nephrology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

    Tivadar Tulassay

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  1. Andrea Kerti
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  15. Tivadar Tulassay
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  16. Kálmán Tory
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Correspondence to Kálmán Tory.

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Kerti, A., Csohány, R., Szabó, A. et al. NPHS2 p.V290M mutation in late-onset steroid-resistant nephrotic syndrome. Pediatr Nephrol 28, 751–757 (2013). https://doi.org/10.1007/s00467-012-2379-2

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  • DOI: https://doi.org/10.1007/s00467-012-2379-2

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