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

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 (), in children with UTI. We determined absolute DNA copy number (CN) of in children with UTI. In this case-control study, we utilized multiple complementary methods to determine the genomic CN of . Children with ( = 370) and without ( = 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 , while 31% of children with UTI and no VUR and 7% of children with UTI and VUR had a single copy of the gene. Using immunostaining, we localized expression postnatally to the bladder and renal epithelia. Mice were also challenged with two uropathogenic strains, and mRNA was quantified. This study represents the first report of 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 in innate immunity.