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Updated: Dec 24, 2025
Cell-Free DNA Integrity Analysis in Urine Samples
Published on: January 5, 2017
DCHS1 DNA copy number loss associated with pediatric urinary tract infection risk
Aslam H Qureshi1,2, Dong Liang3, Jorge Canas3
1Division of Pediatric Nephrology, Department of Pediatrics, University of Tennessee Health Science Center, USA.
Insights
A novel gene, Dachsous Cadherin-Related 1 (DCHS1), is linked to urinary tract infections (UTI) in children. Reduced DCHS1 gene copies were found in children with UTI, suggesting a role in innate immune defense against infection.
Area of Science:
- Genetics
- Immunology
- Pediatrics
Background:
- Urinary tract infections (UTI), often linked with vesicoureteral reflux (VUR), are a significant risk factor for developing chronic kidney disease.
- Genetic factors, particularly in innate immune defenses, play a crucial role in susceptibility to UTIs.
Purpose of the Study:
- To investigate the potential role of the novel gene Dachsous Cadherin-Related 1 (DCHS1) in pediatric urinary tract infections.
- To determine the association between DCHS1 DNA copy number (CN) and the occurrence of UTI in children, with or without VUR.
Main Methods:
- A case-control study comparing DCHS1 genomic copy number in children with UTI (n=441) and healthy controls (n=491).
- Utilized multiple complementary methods to accurately determine DCHS1 copy number.
- Investigated DCHS1 expression in bladder and renal epithelia via immunostaining and quantified Dchs1 mRNA in mice challenged with E. coli.
Main Results:
- A significantly higher prevalence of single-copy DCHS1 was observed in children with UTI (31% without VUR, 7% with VUR) compared to controls (<1%).
- DCHS1 was localized to the bladder and renal epithelia postnatally.
- Dchs1 mRNA levels were quantified in a mouse model of UTI.
Conclusions:
- This study is the first to report an association between DCHS1 and pediatric UTI.
- Reduced DCHS1 gene copy number may indicate a compromised innate immune defense in the lower urinary tract.
- Further research is warranted to elucidate the precise role of DCHS1 in innate immunity and urinary tract defense.
Abstract:
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.
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