Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Mar 6, 2018; 7(2): 65-70
Published online Mar 6, 2018. doi: 10.5527/wjn.v7.i2.65
Genetic defects in ciliary genes in autosomal dominant polycystic kidney disease
Katarína Skalická, Gabriela Hrčková, Anita Vaská, Ágnes Baranyaiová, László Kovács
Katarína Skalická, Gabriela Hrčková, Anita Vaská, Ágnes Baranyaiová, László Kovács, Laboratory of Clinical and Molecular Genetics, Department of Paediatrics, Faculty of Medicine, Comenius University and University Children’s Hospital, Bratislava 83340, Slovakia
Author contributions: Skalická K and Kovács L substantially contributed to the design of the study; Skalická K, Hrčková G, Vaská A and Baranyaiová A performed the research and analyzed of data; all authors drafted the article and approved the final version of the article to be published.
Supported by Slovak Research and Development Agency under Contract, No. APVV-14-0234.
Institutional review board statement: Our study was approved by the Children’s University Hospital Ethics Committee and informed consent was provided by all patients at the inception of the study.
Conflict-of-interest statement: The authors have declared that no conflict of interest exists.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: In our study, ARRIVE Guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Katarína Skalická, MSc, PhD, Research Scientist, Laboratory Diagnostician in Clinical Genetics and Researcher, Laboratory of Clinical and Molecular Genetics, Department of Paediatrics, Faculty of Medicine, Comenius University and University Children’s Hospital, Limbova 1, Bratislava 83340, Slovakia. genlab@dfnsp.sk
Telephone: +421-2-59371873 Fax: +421-2-59371850
Received: December 12, 2017
Peer-review started: December 13, 2017
First decision: December 27, 2017
Revised: December 31, 2017
Accepted: February 4, 2018
Article in press: February 4, 2018
Published online: March 6, 2018
Abstract
AIM

To evaluate the genetic defects of ciliary genes causing the loss of primary cilium in autosomal dominant polycystic kidney disease (ADPKD).

METHODS

We analyzed 191 structural and functional genes of the primary cilium using next-generation sequencing analysis. We analyzed the kidney samples, which were obtained from 7 patients with ADPKD who underwent nephrectomy. Each sample contained polycystic kidney tissue and matched normal kidney tissue.

RESULTS

In our study, we identified genetic defects in the 5 to 15 genes in each ADPKD sample. The most frequently identified defects were found in genes encoding centrosomal proteins (PCM1, ODF2, HTT and CEP89) and kinesin family member 19 (KIF19), which are important for ciliogenesis. In addition, pathogenic mutations in the PCM1 and KIF19 genes were found in all ADPKD samples. Interestingly, mutations in the genes encoding the intraflagellar transport proteins, which are the basis of animal models of ADPKD, were only rarely detected.

CONCLUSION

The results of our study revealed the actual state of structural ciliary genes in human ADPKD tissues and provided valuable indications for further research.

Keywords: Polycystic kidney disease, Primary cilium, Ciliary genes, Next-generation sequencing, Genetic variants

Core tip: Many studies have confirmed that the loss of primary cilia promotes renal cyst formation in autosomal dominant polycystic kidney disease (ADPKD). However, these studies are based on mouse models by the inactivation of various ciliary genes, and the actual status of these genes in human ADPKD tissues is unknown. In our study, we analyzed genetic defects in ciliary genes in the human polycystic kidney tissues and matched normal kidney tissues by next-generation sequencing. We found that the loss of the primary cilia in the human ADPKD tissues may be predominantly caused by defects of centrosomal proteins and KIF19 protein.