Copy-number variation associated with congenital anomalies of the kidney and urinary tract

Pediatr Nephrol. 2015 Mar;30(3):487-95. doi: 10.1007/s00467-014-2962-9. Epub 2014 Oct 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • DNA Copy Number Variations*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Polymorphism, Single Nucleotide
  • Urogenital Abnormalities / genetics*
  • Vesico-Ureteral Reflux / genetics*

Supplementary concepts

  • Cakut