Volume 4 Supplement 1

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

Open Access

Multidisciplinary nephrogenetic outpatient clinic combined with diagnostic exome sequencing for improved diagnostics and treatment

  • D Lugtenberg1,
  • H Arts1,
  • J Van Reeuwijk1,
  • E Cornelissen2,
  • J Deegens3,
  • J Hofstra3,
  • J Wetzels3,
  • C Gilissen1,
  • R Roepman1,
  • E Kamsteeg1 and
  • E Bongers1
Cilia20154(Suppl 1):P53

DOI: 10.1186/2046-2530-4-S1-P53

Published: 13 July 2015

Single gene disorders are estimated to account for ~30% of children and ~10% of adult patients attending renal outpatient services. For mutation detection by exome sequencing, deep phenotyping, reverse phenotyping and family history information are important. A multidisciplinary nephrogenetic outpatient clinic for children and adult patients with (genetic) kidney diseases has been established by a team of (pediatric) nephrologists and a clinical geneticist in the Radboudumc. Clinical exome sequencing for a broad spectrum of isolated- and syndromic renal (ciliary) disorders has been developed. The approach consists of a two-tier analysis in which the first step is to screen for pathogenic variants in genes that are known to be mutated in renal diseases (170 genes) or (renal) ciliopathies (125 genes). If causative mutations are not identified in the first step, the complete exome data set can be analysed with informed consent. The first results with the renal disease gene panel in 35 unrelated patients with undiagnosed renal disease led to pathogenic mutations in the CC2D2A, CLCN5, NPHP1 and UMOD gene, detected in four cases and in six other cases likely pathogenic variants needed follow-up studies. Further analysis of the complete exome data set in 13 patients, revealed possible pathogenic mutations in two cases. While variant and copy number variation analysis in the rest of exome is expected to further increase diagnostic yield, we can already conclude that the combination of the multidisciplinary outpatient clinic with diagnostic exome sequencing provides a powerful tool for detecting causative mutations of renal disease.

Authors’ Affiliations

(1)
Human Genetics, Radboud University Medical Center
(2)
Pediatric Nephrology, Radboud University Medical Center
(3)
Nephrology, Radboud University Medical Center

Copyright

© Lugtenberg 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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