Volume 4 Supplement 1

Proceedings of the Second International Cilia in Development and Disease Scientific Conference (2014)

Open Access

KOUNCIL: Kidney-Oriented Understanding of Correcting Ciliopathies

  • M Stokman1,
  • M Oud2,
  • J Van Reeuwijk2,
  • M Lilien3,
  • N Van De Kar4,
  • I Nijman1,
  • C Gilissen2,
  • HY Kroes1,
  • E Bongers2,
  • N Geijsen5,
  • E Kamsteeg2,
  • E Cuppen1,
  • R Roepman2,
  • R Giles6,
  • K Renkema1,
  • H Arts2 and
  • N Knoers1
Cilia20154(Suppl 1):P50

DOI: 10.1186/2046-2530-4-S1-P50

Published: 13 July 2015

Objective

Nephronophthisis is an autosomal recessive renal ciliopathy that constitutes the leading monogenic cause of end-stage renal disease in children. The KOUNCIL consortium is a collaboration between the UMC Utrecht, the Radboud UMC Nijmegen and UC London aimed at elucidating the genetic etiology and pathophysiological mechanisms underlying nephronophthisis and identifying drugs that prevent or delay renal insufficiency. Our goal is to improve genome diagnostics, genetic counselling and therapeutic options for nephronophthisis patients.

Methods

We employ next-generation sequencing to identify novel disease genes in 100 nephronophthisis patients included within the AGORA biobank project. The functional effect of novel mutations is assessed using in vitro and in vivo models. Genotypic and phenotypic patient characteristics are registered in a nephronophthisis database, facilitating correlation analyses and identification of early phenotypic markers. Newly identified nephronophthisis-genes are incorporated into diagnostic next-generation sequencing panels of ciliary genes. We use a systems-biology approach to identify and functionally characterize nephronophthisis-associated protein modules. Finally, we use high-throughput repurposing screens in zebrafish embryos to identify FDA-approved drugs that halt renal failure.

Results

With this approach, we expect to uncover the causal mutation in 60-90% of nephronophthisis patients. KOUNCIL members were involved in the recent identification of three novel genes (IFT172, WDR34 and WDR60) for nephronophthisis-related disorders. Clinical guidelines and new diagnostic tools for nephronophthisis are developed and implemented in diagnostics. We expect to identify drugs that can lead to novel therapies for nephronophthisis.

Conclusion

The KOUNCIL study is designed to advance understanding of renal ciliopathies and improve clinical care for nephronophthisis patients.

Authors’ Affiliations

(1)
Medical Genetics, University Medical Center Utrecht
(2)
Human Genetics, Radboud University Medical Center
(3)
Pediatric Nephrology, Wilhelmina Children's Hospital, University Medical Center Utrecht
(4)
Pediatric Nephrology, Radboud University Medical Center
(5)
Hubrecht Institute, University Medical Center Utrecht
(6)
Nephrology and Hypertension, University Medical Center Utrecht

Copyright

© Stokman et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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