This article is part of the supplement: Proceedings of the First International Cilia in Development and Disease Scientific Conference (2012)

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Alteration of nephrocystins and IFT-A proteins causes similar ciliary phenotypes leading to Nephronophthisis

S Saunier1*, AA Bizet1, F Silbermann1, E Filhol1, T Blisnick2, A Henneveu3, E Montenont1, I Perrault4, C Boyle-Feysot5, J-M Rozet4, P Bastin2, HH Arts6, C Antignac1 and AR Benmerah3

Author Affiliations

1 Inserm U983, France

2 Pasteur Institute, CNRS UMR2581, France

3 Inserm U1016, Cochin Institute, France

4 Inserm U781, France

5 Fondation Imagine, Paris, France

6 Radboud University Nijmegen Medical Center, the Netherlands

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Cilia 2012, 1(Suppl 1):P99  doi:10.1186/2046-2530-1-S1-P99

The electronic version of this article is the complete one and can be found online at:

Published:16 November 2012

© 2012 Saunier et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Poster presentation

Nephronophtisis (NPH) is a kidney ciliopathy often associated with extra-renal defects and for which 12 genes (NPHP1-12) have been identified. NPHP1 and NPHP4 control the ciliary access at the transition zone and the velocity of some intraflagellar transport (IFT)/BBS proteins in C.elegans. Recently, in a collaborative effort, we have identified, in families with isolated NPH, mutations in TTC21B as well as in WDR19, which encode the retrograde IFT-A proteins IFT139 and IFT144, respectively. By ciliome sequencing of 1600 candidate genes from 14 NPH patients followed by Sanger sequencing of a cohort of 52 patients, we have found respectively 8 and 7 patients carrying pathogenic missense mutations in genes coding IFT-A proteins, including WDR35, TTC21B and IFT140, which could partially affect their function. Together, these results indicate that IFT-A are involved in nephronophtisis. Moreover, alteration of cilia length was observed in patient kidney, Nphp4-/- mice kidney tubules and NPHP1 or NPHP4 knockdown IMCD3 cell lines. In these cells, primary cilia present swellings at the distal region accompanied by an accumulation of IFT-B at the base and the tip, similar to what was observed in IFT-A mutants, suggesting a possible alteration of retrograde transport. Additionally, ARL13B, a small GTPase required for proper cilium shape and IFT stability, is absent along the axoneme of NPHP4-KD-IMCD cells. By controlling the entry of ciliary components at the transition zone, NPHP1 and NPHP4 may modulate IFT-A cargos thus participating in the same pathway (i.e. Wnt/PCP), alteration of which would lead to renal lesions observed in nephronophthisis.