NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome

A Correction to this article was published on 01 May 2000

Abstract

Familial idiopathic nephrotic syndromes represent a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. A causative gene for this disease, NPHS2, was mapped to 1q25–31 and we report here its identification by positional cloning. NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier.

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Figure 1: Map of the NPHS2 region.
Figure 2: Tissue distribution and relative expression of NPHS2 in human tissues.
Figure 3: Detection of NPHS2 mutations.
Figure 4: Amino-acid sequence comparison of human podocin, human stomatin and C. elegans MEC-2.
Figure 5: In situ hybridization of antisense (ad) and sense (e) NPHS2 riboprobes labelled with digoxigenin ( a,b) or [35S]UTP (ce).

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Acknowledgements

We thank the patients and their families for participation; E. Al-Sabban, L. Alsford, J.L. André, F. Bouissou, S. Caliskan, E. Kuwertz-Bröcking, B. Lange, J. Nauta and W. Proesmans for referring patients; V. Kalatzis and L. Heidet for critical reading of the manuscript; V. Chauvet for help with in situ hybridization; and Y. Deris for assistance with figure preparation. This study was supported in part by the Association pour l'Utilisation du Rein Artificiel and the Fondation pour la Recherche Médicale. N.B. was supported by grants from the Association Française contre les Myopathies and, subsequently, the Programme Hospitalier de Recherche Clinique.

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Correspondence to Corinne Antignac.

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Note added in proof:

During the publishing process, J. Kaplan et al. have shown that mutations in ACTN4, mapped to 19q13 and encoding a-actinin-4, an actin-filament cross linking protein, cause autosomal FSGS (ref. 40).

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Boute, N., Gribouval, O., Roselli, S. et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 24, 349–354 (2000). https://doi.org/10.1038/74166

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