Abstract
Background
The most common cause of end-stage renal disease in children can be attributed to congenital anomalies of the kidney and urinary tract (CAKUT). Despite this high incidence of disease, the genetic mutations responsible for the majority of CAKUT cases remain unknown.
Methods
To identify novel genomic regions associated with CAKUT, we screened 178 children presenting with the entire spectrum of structural anomalies associated with CAKUT for submicroscopic chromosomal imbalances (deletions or duplications) using single-nucleotide polymorphism (SNP) microarrays.
Results
Copy-number variation (CNV) was detected in 10.1 % (18/178) of the patients; in 6.2 % of the total cohort, novel duplications or deletions of unknown significance were identified, and the remaining 3.9 % harboured CNV of known pathogenicity. CNVs were inherited in 90 % (9/10) of the families tested. In this cohort, patients diagnosed with multicystic dysplastic kidney (30 %) and posterior urethral valves (24 %) had a higher incidence of CNV.
Conclusions
The genes contained in the altered genomic regions represent novel candidates for CAKUT. This study has demonstrated that a significant proportion of patients with CAKUT harbour submicroscopic chromosomal imbalances, warranting screening in clinics for CNV.
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Acknowledgments
The authors thank the families for their participation in this study, which was supported by a National Health and Medical Research Council Project Grant (APP1021532).
URLs for data presented herein are as follows:
DECIPHER,
https://decipher.sanger.ac.uk/
GUDMAP Genitourinary Database Molecular Anatomy Project,
National Center for Biotechnology Information,
Online Mendelian Inheritance in Man (OMIM),
UCSC Genome Browser Home,
CHOPS, http://cnv.chop.edu/
International Standards for Cytogenomic Arrays (ISCA),
http://www.iscaconsortium.org/
Database of Genomic Variants (DGV)
http://dgv.tcag.ca/dgv/app/home
Funding
National Health and Medical Research Council Project Grant (APP1021532)
Note added in proof
Recently, Epha4 –/–; Epha7 –/–mice have been reported to display hydroureter, megaureter and hydronephrosis, therefore EPHA7 can be considered as a candidate for Case 1 (Table 2) [48].
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Caruana, G., Wong, M.N., Walker, A. et al. Copy-number variation associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 30, 487–495 (2015). https://doi.org/10.1007/s00467-014-2962-9
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DOI: https://doi.org/10.1007/s00467-014-2962-9