DCHS1 DNA copy number loss associated with pediatric urinary tract infection risk

Innate Immun. 2020 Aug;26(6):473-481. doi: 10.1177/1753425920917193. Epub 2020 Apr 15.


Urinary tract infections (UTI), associated with vesicoureteral reflux (VUR), can lead to chronic kidney disease. Genetic alterations in the innate immune defenses contribute to UTI risk. We investigated a novel gene, Dachsous Cadherin-Related 1 (DCHS1), in children with UTI. We determined absolute DNA copy number (CN) of DCHS1 in children with UTI. In this case-control study, we utilized multiple complementary methods to determine the genomic CN of DCHS1. Children with (n = 370) and without (n = 71) VUR from two well-phenotyped clinical trials of UTI were copy-typed and compared to 491 healthy controls with no known history of VUR or UTI. Less than 1% of controls had a single copy of DCHS1, while 31% of children with UTI and no VUR and 7% of children with UTI and VUR had a single copy of the DCHS1 gene. Using immunostaining, we localized expression postnatally to the bladder and renal epithelia. Mice were also challenged with two uropathogenic Escherichia coli strains, and Dchs1 mRNA was quantified. This study represents the first report of DCHS1 in association with pediatric UTI. We hypothesize that its role in innate immunity is critical to lower urinary tract defense. Further investigation is required to determine the role of DCHS1 in innate immunity.

Keywords: DNA CN variations; pediatrics; urinary tract infections; vesicoureteral reflux.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Child
  • Child, Preschool
  • DNA Copy Number Variations
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype*
  • Humans
  • Infant
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Risk
  • Urinary Tract Infections / genetics*


  • CDHR6 protein, human
  • Cadherin Related Proteins
  • Cadherins